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Harvard Medical School Curriculum Vitae

Date Prepared: Dec 06, 2019

Name: Rohit N. Kulkarni

Office Address: 1 Joslin Place, Boston, MA 02215

Home Address: 274 Lagrange Street, Chestnut Hill, MA 02467-3031

Work Phone: 617-309-3460

Work E-Mail: rohit.kulkarni@joslin.harvard.edu

Work FAX: 617-309-3476

Education 1986 M.B., B.S. Medicine and Surgery, Bangalore Medical College, Bangalore University,

India 1990 M.D. Physiology (Medicine), St. John’s Medical College, Bangalore

University, India 1996 Ph.D. Biochemistry, Royal Postgraduate Medical School, University of

London, England; Advisor: Sir Stephen R. Bloom, FRS Postdoctoral Training 5/85-4/86 Resident Intern Victoria & Vani Vilas Children’s Hospital, Bangalore, India 5/86-1/87 Research Fellow Clinical Physiology and Nutrition Research Center, St. John’s Medical College, Bangalore, India 1/87-12/89 Research Officer Clinical Physiology and Nutrition Research Center, St. John’s (funded by UN Medical College, Bangalore, India University) 4/91-12/96 Research Fellow Endocrinology, Francis Fraser Labs, Division of Endocrinology, Hammersmith Hospital, London. Laboratory of Sir Stephen R. Bloom FRS 4/97-8/99 Postdoctoral Fellow Cellular & Molecular Physiology, Joslin Diabetes Center, Boston, MA Laboratory of Prof. C. Ronald Kahn, M.D. 9/99-10/2000 Research Associate Cellular & Molecular Physiology, Joslin Diabetes Center Laboratory of Prof. C. Ronald Kahn, M.D.

Faculty Academic Appointments 1/90-3/91 Lecturer Department of Physiology/Clinical Nutrition, St. John’s Medical

College 9/99-3/2004 Instructor Medicine, Harvard Medical School (HMS), Boston 4/04-9/09 Assistant Professor Medicine, HMS 10/09-11/15 Associate Professor Medicine, HMS 11/15- Professor Medicine, HMS Appointments at Hospitals/Affiliated Institutions

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1/96-12/96 Hon. Clinical Department of Metabolic Medicine, Hammersmith Hospital Registrar 10/2000-3/04 Assistant Cellular and Molecular Physiology, Joslin Diabetes Center Investigator 4/04-4/13 Investigator Islet Cell and Regenerative Biology, Joslin Diabetes Center 4/13- Senior Investigator Islet Cell and Regenerative Biology, Joslin Diabetes

Center 4/17- Co-Head Islet Cell and Regenerative Biology, Joslin Diabetes

Center 11/17- Margaret A. Congleton Endowed Chair Islet Cell and Regenerative Biology, Joslin Diabetes

Center 05/19-10/19 Adjunct Professor Institute of Molecular Health Sciences, ETH, Zurich Other Professional Positions * reviewed by Broad Institute Review Committee; approved by Broad Institute Collaboration Coordinating Committee **nominated by Douglas Melton, PhD, co-Director, HSCI 2010- Member Sanofi Advisory Board (global healthcare company) (1-2 meetings/year) 2013- Associate Member* Broad Institute of Harvard and the Massachusetts Institute of

Technology (MIT), Cambridge, MA 2007-14 Adjunct Faculty** Harvard Stem Cell Institute (HSCI), Boston and Cambridge, MA 2014- Principal Faculty** HSCI Major Administrative Leadership Positions 2002-2012 Director Diabetes Endocrinology Research Center (DERC, now Diabetes Research Center (DRC)) Specialized Assay Core, Joslin Diabetes Center 2004- Organizer Boston-Ithaca Islet Group Meetings (2-day meetings, every 3 years) 2010-2016 Associate Director Joslin Induced Pluripotent Stem Cells (iPS) Core, DRC, Joslin Diabetes Center 2012-2013 Director Specialized Assay Core, Joslin Diabetes Center 2014 Lead Organizer Islet Keystone Symposium (D3), Keystone, CO (April 2014) (nominated by Keystone Advisory Council for this role) 2015 Co-organizer Diabetes (J3) Keystone Symposium - joint with Obesity and Adipose Tissue Biology (J4) (Jan 2017) 2017-2019 Associate Director Joslin DRC 2019- Director Pilot and Feasibility Program, Joslin DRC Committee Service Local 2002-2016 Member, Fellowship Committee, Joslin Diabetes Center 2004-2018 Member, Institutional Animal Care and Use (IACUC) Committee, Joslin Diabetes Center 2004- Pre Qualifying and PhD Examiner, Harvard University 2004, PhD Examiner - Juliana Brown; Biological and Biomedical Sciences (BBS)

2011-12, PhD Thesis Defense Committee - Lucy Soo Yon Jun; BBS; 2015, Pre-Qualifying Exam Committee - Zhi Wei Tan; Chemical Biology Program, HMS

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2007- Thesis Advisory Committee - Sara Vallerie, PhD Candidate; Biological Sciences in Public Health, Harvard University; Edwin Rosado, PhD Candidate; Stem Cell and Regenerative Biology, Harvard University

2011- Undergraduate Thesis Examiner; Harvard College PhD Thesis Defense Committee - Lucy Soo Yon Jun; Biological and Biomedical Sciences, Harvard University 2018- Promotions Committee, Department of Medicine, Brigham and Women’s Hospital, HMS Regional 2004- Pre Qualifying and PhD Examiner, University of Massachusetts, Worcester, MA 2004, PhD Examiner - Kathryn Lipson 2012, PhD Examiner - Christine Oslowski National 2013- National Institute of Child Health and Human Development (NICHD) Working Group Member: Diabetes Type 1 Biomarkers International 2004- PhD Examiner - Kathryn Aston-Mourney; University of Melbourne, Victoria, Australia 2010- PhD Examiner - Diana Choi; University of Toronto, Ontario, Canada 2011- PhD Examiner - Veronica Jimenez; Universitat Autonoma de Barcelona (UAB, Autonomous University of Barcelona), Catalonia, Spain 2011- Master’s Thesis Defense Committee - Dario Ferreira De Jesus; Universidade de Tras-os-Montes

e Alto Douro (UTAD, University of Trás-os-Montes and Alto Douro), Portugal Professional Societies 1992-1996 Member British Endocrine Society 1992-1996 Member Biochemical Society 1993-1996 Member British Diabetic Association 1996-1998 Member New York Academy of Sciences 1997- Member Professional Section, American Diabetes Association (ADA) 2014-16 Member, Scientific Planning Committee 1999- Member Endocrine Society 2001- Member European Association for the Study of Diabetes 2007- Elected American Society for Clinical Investigation (ASCI) Member 2014- Elected Association of American Physicians (AAP) Member Grant Review Activities 2004- Ad hoc Reviewer National Institutes of Health (NIH), Diabetes Research and Training Center (DRTC), American Institute for Biological Studies 2007-2011 Permanent Reviewer ADA Scientific Grants Review Committee 2004-2010 Ad hoc Reviewer NIH Cellular Aspects of Diabetes and Obesity (CADO) Study

Sections, Special Emphasis Panels (SEP) 2007 Ad hoc Reviewer Wellcome Trust 2007 Ad hoc Reviewer Medical Research Council (United Kingdom (UK)) 2007-8 Ad hoc Reviewer Small Business Innovation Research/Small Business Technology

Transfer (SBIR/STTR) Endocrinology, Metabolism, Nutrition and Reproductive Sciences (EMNR-E(10)) Grant Review Committee

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2008 Ad hoc Reviewer Fondazione Roma (Italy) 2008 Ad hoc Reviewer Beta Cell Biology Consortium, National Institutes of Health 2008 Ad hoc Reviewer Institut national de la santé et de la recherche médicale (INSERM,

French Institute of Health and Medical Research) 2008 Ad hoc Reviewer Science Foundation Ireland 2008, 12, 15 Ad hoc Reviewer Diabetes UK 2008- Ad hoc Reviewer Juvenile Diabetes Research Foundation 2009 Ad hoc Reviewer Bergen Research Foundation (Norway) 2009 Ad hoc Reviewer Genome British Columbia Strategic Opportunities Fund 2009 Ad hoc Reviewer Academy of Finland 2010 Ad hoc Reviewer European Commission 7th Framework Program for Research and

Technological Development (FP7) 2011-2015 Permanent Member NIH Cellular Aspects of Diabetes and Obesity (CADO) Study

Section 2012, 16 Ad hoc Reviewer Israel Science Foundation 2012 Ad hoc Reviewer French National Research Agency 2012, 16 Ad hoc Reviewer Research Grants Council (Hong Kong) 2012 Ad hoc Reviewer Swiss National Science Foundation 2013 Ad hoc Reviewer German Research Foundation 2014 Ad hoc Reviewer Qatar Biomedical Research Institute 2015 Ad hoc Reviewer The Knut and Alice Wallenberg Foundation 2015 Ad hoc Reviewer Novo Nordisk Foundation 2015 Ad hoc Reviewer Research Grants Council, Hong Kong 2015 Ad hoc Reviewer NIH Study Section, Special Emphasis Panel 2016 Ad hoc Reviewer NIH Study Section, Molecular and Cellular Endocrinology (MCE) Editorial Activities

• Ad hoc Reviewer Nature Science Cell Cell Metabolism Cell Stem Cell Nature Genetics Nature Medicine Journal of Clinical Investigation Science Translational Medicine EMBO Journal (European Molecular Biology Organization) EMBO Reports

Endocrinology Journal of Cell Biology Molecular Cell Biology Journal of Biological Chemistry Genomics Molecular and Cellular Endocrinology Diabetes Diabetologia Molecular Endocrinology International Journal of Biochemistry and Cell Biology

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Journal of Clinical Endocrinology and Metabolism Diabetes/Metabolism Research & Reviews PLoS Biology (Public Library of Science) PLoS One Biochemistry and Cell Biology

Molecular Metabolism Journal of Endocrinology eLife

• Other Editorial Roles 2006- 2008 Editorial Board Diabetes 2006- 2010 Editorial Board Journal of Endocrinology 2006- 2012 Editorial Board Journal of Clinical Investigation 2010- 2014 Editorial Board Endocrinology 2013- Editorial Board Journal of Biological Chemistry 2017- Editorial Board Journal of Clinical Investigation

Honors and Prizes 1986 Distinction in Biochemistry, Bangalore Medical College, Bangalore University 1990 Young Scientist Award, National Institute of Nutrition, India 1991-1994 Overseas Research Students (ORS) Award, Hammersmith Hospital, London 1991-1994 Weston Scholarship, Royal Postgraduate Medical School, London, Research 1998-2000 F32 National Research Service Award (National Institutes of Health) 2000-2005 K08 Clinician Scientist Development Award (National Institutes of Health) 2005 K08 Best Presentation and Trainee Travel Awards, ASCI Meeting, Chicago 2007 Endocrine Society Ernst Oppenheimer Laureate Award 2007 Elected to American Society for Clinical Investigation 2009 Merck-Frosst Distinguished Speaker, Univ. British Columbia 2010 Endocrine Society Visiting Professorship in Endocrine Pancreas Preservation 2014 Elected to Association of American Physicians 2014 James H. Horner Distinguished Visiting Professorship, UTHSC 2015 Prof. M.S.S. Ahuja Oration, Research Society for Study of Diabetes in India, Lucknow 2015 Dr. H.J. Mehta Memorial Oration, St. John’s Medical College Alumni Association 2015 M.A., (Honorary), Harvard Medical School, Boston 2017 Margaret A. Congleton Endowed Chair 2018 Albert Renold Prize and Lecture, European Association for Study of Diabetes 2020 Jay Santiago Lecture, Washington Univ. School of Medicine, St. Louis Report of Funded and Unfunded Projects Past Funded Projects 1998-2000 National Research Service Award F32DK009825 Islet growth in animal models of insulin resistance Goals: To characterize the insulin secretory pattern and growth of islets isolated from wild type and models of insulin resistance showing islet hyperplasia on different genetic backgrounds. To characterize the role of the proteins in the signaling pathways using cell lines derived from the knockout mice. 2000-2005 PI K08 Mentored Clinician Scientist Development Award Insulin and glucose signaling pathways in islet beta cells

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Goals: To understand the mechanisms by which the insulin-signaling proteins modulate beta-cell function and to delineate the cross-talk between the insulin- and glucose-signaling pathways. Specific Aims: 1) to identify the cellular mechanisms by which proteins in the insulin-signaling pathway modulate insulin secretion and synthesis in response to different stimuli, 2) to determine the alterations in glucose metabolism in islets/beta-cells isolated from mice lacking IR and IRS proteins and to study the effects of re-expression of the proteins in the knockout cell lines, and 3) to evaluate the expression of insulin signaling proteins and glucose metabolism in islets isolated from rodent models of diabetes. Role as PI: Planning, designing and executing experiments. Mentoring post-doctoral Fellows, Research Assistants, Graduate and summer students, and interns. Writing manuscripts, fellowship and grant applications. 2002-2007 Core Director NIH/DERC 5P30DK36836 (PI: Weir) DERC Specialized Assay Core Major goals: provide a comprehensive array of services for the training of Post-doctoral fellows and students for performing research in the academic setting of the Joslin Diabetes Center. PI’s role is to direct the working of the Special Assay Core that provides assays for measuring hormones and metabolites for research personnel. 2003-2005 PI Vanderbilt University / NIH U19DK42502 Title: Search for hepatic-derived islet cell growth factor(s) Major goals: Examine potential growth factors that are derived from the liver in the regulation of beta-cell proliferation. PI’s role is to plan the experiments in the mouse models and at the bench, analyze and interpret the data, troubleshoot problem areas, and write manuscripts. 2003-2005 PI Adler Foundation Grant Title: Investigation of novel factors that determine β-cell growth and replication Major goals: To examine potential role of circulating and cell autonomous factors that modulate beta-cell growth. PI’s role is to plan experiments, mentor post-doctoral fellow, interpret the data and write manuscripts. 2004-2005 PI NIH – R03 5R03DK066207 Title: Leptin modulation of insulin action in the islet beta cell Major goals: Understand the potential role of cross talk between leptin and insulin in the regulation of islet proliferation and secretory function. PI’s role is to plan the experiments, trouble shoot problem areas, supervise the research assistant, interpret and analyze the data and write manuscripts. 2004-2005 PI Compugen Title: Potential biological effects of GLP-1 variant (vGLP-1) Major goals: Study the effects of variants of glucagon-like-peptide-1 in the regulation of beta-cell proliferation. PI’s role is to plan the experiments in cells, analyze and interpret the data, and write a report. 2004-2007 PI ADA Research Award 7-04-RA-55 Title: Role of insulin/IGF-1 signaling in modulation of beta-cell function and growth Major goals: Investigating the role of insulin and insulin-like growth-factor-I signaling in the regulation of alpha-cell secretory function and growth. PI’s role is to plan experiments, mentor post-doctoral fellow, interpret the data and write manuscripts. 2004-2010 PI NIH – R01 DK67536 Title: Role of insulin/IGF-1 receptors in beta-cell survival Major goals: Exploring the molecular mechanism and signaling pathways that link growth factor signaling (especially insulin and insulin like-growth-factor-I) with key transcription factors and proteins involved in beta-cell proliferation and survival. PI’s role is to plan the studies in creating novel mouse models, mentor the post-doctoral fellows and research assistants working on the project, interpret the data and write manuscripts.

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2004-2010 PI NIH – R01 DK68721 Title: Dissecting the death pathway in beta-cells Major goals: Understanding the role of the growth factor signaling proteins (insulin and insulin like-growth-factor-I) in modulating the proteins involved in mitochondrial biology (eg. Bax. Bak, and Mcl-1) in the overall regulation of beta-cell survival. PI’s role is to plan the studies in creating novel mouse models, mentor the post-doctoral fellows and research assistants working on the project, interpret the data and write manuscripts. 2005-2007 PI Harvard Stem Cell Institute Title: Identification of beta-cell growth factor Major goals: To identify a potential growth factor that promotes proliferation of beta cells in mouse models of insulin resistance. PI’s role is to plan the studies, interpret the data, and write manuscripts. 2005-2009 PI Novartis Title: Effect of LAF237 on pancreatic beta cell function and morphology using the beta-cell specific insulin receptor knockout mouse Major goals: Examining the effects of the compound LAF237 (glucagon-like-peptide-1 analog) on the regulation of β-cell proliferation in a mouse model of diabetes. PI’s role is to mentor the post-doctoral fellow, assist in planning studies, interpret the data and write manuscripts. 2006-2006 PI Takeda Travel Funds Title: Travel Fellowships for post-doctoral Fellows. PI’s role is to obtain travel funds for Fellows to attend scientific meetings. 2006-2009 PI HSCI Weir Project 2 Title: Investigating beta-cell replication in the Liver-Specific Insulin Receptor Knockout (LIRKO) mouse model Major goals: Investigating the molecular mechanism and identifying the signaling proteins involved in the replication of pancreatic beta cells in a mouse model of insulin resistance. PI’s role is to plan experiments, mentor post-doctoral fellow, interpret the data and write manuscripts. 2007-2008 PI Endocrine Fellow Foundation Title: Role of circulating growth factors in alpha cells Major goals: Identification of potential circulating growth factors in the proliferation of pancreatic a-cells. PI’s role is to plan studies, mentor the post-doctoral fellow, troubleshoot problem areas, interpret the data and write manuscripts. 2007-2008 PI Eli Lilly Research Agreement Title: Exploring the presence of a novel circulating islet alpha-cell growth factor Major goals: To explore the presence of a circulating growth factor that promotes a-cell proliferation using a parabiosis mouse model. PI’s role is to plan studies, mentor the post-doctoral fellow, interpret the data and write manuscripts. 2007-2008 PI Takeda Travel Funds Title: Travel Fellowships for post-doctoral fellows. PI’s role is to obtain travel funds for fellows to attend scientific meetings. 2007-2008 PI JDRF Grant 5-2007-645 Title: Studying the role of insulin receptor substrates in beta-cell proliferation Major goals: To investigate the role of different insulin receptor substrates (1,2,3, and 4) in the modulation of pancreatic beta-cell growth and survival. PI’s role is to plan studies, interpret and analyze the data and write manuscripts.

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2007-2009 PI Merck Title: Effects of GLP-1 on alpha-cell function Major goals: Examining the effects of glucagon-like-peptide-1 in the regulation of glucagon secretion from pancreatic alpha cells. PI’s role is mentoring the post-doctoral fellow, planning studies in mouse models and in cell lines, interpreting data and writing manuscripts. 2007-2010 PI NIH - R21 5R21DK075766 Title: Role of leptin in islet growth Major goals: Understanding the molecular mechanisms and pathways that link leptin signaling with growth and function of pancreatic beta cells. PI’s role is planning the experiments, mentoring the post-doctoral fellow and research assistants, interpreting data and writing manuscripts. 2007-2010 PI ADA Research Award 7-07-RA-84 Title: Leptin modulation of islet lipid metabolism Major goals: Investigating the effects of leptin in the beta cell with a focus on islet lipid metabolism. PI’s role is to mentor the post-doctoral fellow, assist in planning studies, interpret the data and write manuscripts. 2007-2012 Core Director NIH/DERC 5P30DK36836 (PI: Weir) Title: Specialized Assay Core Program Grant Major goals: provide a comprehensive array of services for the training of post-doctoral fellows and students for performing research in the academic setting of the Joslin Diabetes Center. PI’s role is to direct the working of the Special Assay Core that provides assays for measuring hormones and metabolites for research personnel. 2008-2009 PI SysCode Training Grant/BWH RL1EB008539-01 Title: Defining the islet proteome Major goals: To define the proteome of islets isolated from mice of different ages ranging from neonatal to adult. PI’s role is to plan studies, mentor the post-doctoral fellow, troubleshoot problem areas, interpret the data and write manuscripts. 2008-2009 PI AstraZeneca Title: Role of PPAR-gamma and PGC1−alpha in islet metabolism Major goals: Examine the role of PPAR-gamma and PGC1−alpha in the regulation of beta-cell proliferation and metabolism. PI’s role is planning the experiments, mentoring the post-doctoral fellow and research assistants working on the project, interpreting the data and write manuscripts. 2008-2011 PI Takeda Title: Effects of pioglitzaone on beta-cell survival in a mouse model of diabetes. Major goals: Understanding the effects of thiozolidinediones in the regulation of beta-cell proliferation. PI’s role is mentoring the research assistant, planning studies at the bench and in the mouse models, interpreting data and writing manuscripts. 2008-2012 PI ADA Mentor Based Fellowship 7-08-MN-32 Title: Role of growth factor and leptin signalling in islet cells Major goals: Understanding the pathways that promote regeneration of pancreatic beta-cells with a focus on proliferation and survival. PI’s role is to mentor the post-doctoral fellow, assist in planning studies, interpret the data and write manuscripts. 2009-2011 PI NIH 3R56DK067536-06S1 American Recovery and Reinvestment Act (ARRA)

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2010-2011 PI NIH 3R56DK067536-06S1 (Supplement) Title: Role of insulin/IGF-1 receptors in beta-cell survival Major goals: Exploring molecular mechanisms and signaling pathways that link growth factor signaling (especially insulin and insulin like-growth-factor-I) in beta-cell proliferation and survival. PI’s role is to plan the studies in creating novel mouse models, mentor the post-doctoral fellows and research assistants working on the project, interpret the data and write manuscripts. 2009-2012 PI NIH R21 RR-24905 Title: Characterization of the inducible beta-cell-specific p53 knockout mouse. Major goals: Create and characterize a beta-cell-specific inducible p53 knockout mouse to examine its role in the proliferation and survival of beta cells. PI’s role is to plan the experiments, mentor the post-doctoral fellows and research assistants working on the project, interpret the data and write manuscripts. 2010-2015 PI NIH 2RO1DK067536-06 Title: Role of insulin/IGF-1 receptors in beta-cell survival Major goals: Exploring molecular mechanisms and signaling pathways that link growth factor signaling (especially insulin and insulin like-growth-factor-I) in beta-cell proliferation and survival. PI’s role is to plan the studies in creating novel mouse models, mentor the post-doctoral fellows and research assistants working on the project, interpret the data and write manuscripts. 2011-2013 PI JDRF Innovative Grant 5-2011-74 Title: Analyses of protective factors using induced pluripotent stem cells Major goals: The aim of this project is to derive induced pluripotent stem cells from skin biopsies from patients with long-standing type 1 diabetes (Joslin Medalist patients) and differentiate these cells into endothelial cells that are targets of complications. 2012-2013 PI HSCI PO1 Pilot Grant Title: Significance of insulin and insulin-like growth factors (IGFs) for maintenance of pluripotency of human pluripotent stem cells (hPSCs) Major goals: Evaluation of the role of insulin receptor versus IGF-1 receptor in the regulation of pluripotency of human ES cells. 2011 - 2014 PI JDRF/Sanofi Grant 17-2011-644 Title: Identification of a liver-derived beta cell growth factor Major goals: The aim of the project is to isolate and identify a circulating growth factor derived from the liver in insulin resistant states. 2008-2014 Co-PI NIH-Subcontract 1R01DK074795 (PI: Smith) Title: Proteomic studies of type 2 diabetes using knockout mouse models. Major Goals: Defining the proteome of islets and plasma isolated from a mouse model of islet growth in response to insulin resistance. PI’s role is mentoring the post-doctoral fellow and research assistant, planning studies, providing mouse models and samples, interpreting data and writing manuscripts. 2012-2014 PI HSCI Seed Grant Title: Significance of MODY genes in the differentiation of iPS cells into insulin-secreting beta cells Major goals: Derive iPS cells from skin biopsies of patients with MODY and differentiate the iPS cells into pancreatic progenitors and beta cells. 2013-2016 Co-PI JDRF Grant

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Title: Inhibition of HDAC3 to promote beta-cell survival Major goals: Validate the approach of inhibiting the activity of the enzyme histone deacetylase 3 (HDAC3) with a chemical compound to protect pancreatic beta cells from inflammatory cell death. 2015-2016 PI MedImmune Title: Identification of beta cell growth factors Major goals: Studies are focused on identifying novel proteins that enhance the proliferation of human beta cells and improve glucose homeostasis. 2011- 2017 Multi-PI RO1 (Doria PI; Kulkarni Co-PI) NIH 2RO1DK055523-10A2 Title: Search for new MODY genes and molecular studies of their function in beta cells Major goals: The aim of this project is investigate the molecular pathways that underlie the role of the BLK gene in islet cell function and proliferation. 2012-2017 Associate Director, iPS Core, DRC, Joslin 2.5% salary support (2.5% effort) Specific aims are: 1) To implement and maintain a reliable, cost-effective facility for the standardized isolation, culture, and reprogramming of human fibroblasts to generate validated iPS cells from skin-punch biopsy of diabetic and control subjects. 2) To provide DRC Investigators with validated iPS cells, as well as education and training regarding optimal use of these cells in diabetes-related studies. 3) To continually update methods and models in response to researcher needs and new scientific developments. 2016-2017 Multi-PI JDRF Grant (PI: Cowan; Co-PI: Newgard; Co-PI: Wagner; Co-PI: Kulkarni) Title: Phenotyping beta cells derived from human ES cells Major goals: Perform in vitro and in vivo experiments to examine the phenotype of beta-like cells derived from human ES cells. 2015-2017 PI JDRF Grant Title: The effects of rapidly replicating beta cells in delaying progression of type 1 diabetes Major goals: To investigate the ability of an increase in beta cell replication in promoting the delay in progression of disease in the NOD model of type 1 diabetes. 2010-2018 PI Astra Zeneca Title: Creation and differentiation of iPS cells into islet cells from patients with type 2 diabetes Major goals: This project is focused on the creation of induced pluripotent stem (iPS) cells from skin biopsies from patients with type 2 diabetes and their differentiation into insulin secreting beta cells. 2014-2018 Multi-PI 1UC4 DK104167-01 (Qian PI; Kulkarni PI; Mathews PI) (dollars are for my grant portion) Title: Regulatory Networks and biomarkers of beta cell dysfunction and apoptosis. Major goals: A systems level of understanding of signaling and regulatory networks that trigger early stage beta cell dysfunction in type 1 diabetes. 2017-2018 Co-PI Joslin P & F Grant Title: Evaluating serpinB1 levels in pregnancy Major goals: Assessing the circulating levels of serpinB1 using ELISA and Western blotting in human pregnancy.

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Current Funded Projects 2014-2023 PI NIH 2RO1 DK067536-14 Title: Role of insulin/IGF-1 receptors in beta-cell survival Major goals: Exploring molecular mechanisms and signaling pathways that link growth factor signaling (insulin and insulin like-growth-factor-I) with epigenetic effects in beta-cell biology 2019-2024 Multi-PI (Co-PI) 1 RO1 DK122160-01 Title: Pathways and critical regulators of early β-cell dysfunction in type 1 diabetes. Major goals: Identify mechanisms of islet heterogeneity and early β-cell dysfunction in the progression to T1D onset, and demonstrate a path towards rational selection of therapeutic targets for future preventive strategies. 2018-2023 Multi-PI (Co-PI) 1 RO1 DK117639-01 Title: Interplay between SerpinB1 and TLR2 and TLR4 in beta cell regeneration Major Goals: Investigate the cross talk between the pathways mediated by SerpinB1 and the proteins downstream of the toll like receptors in modulating human beta cell regeneration. 2017-2021 PI 1 UC4 DK116278-01 Title: Interrogation of Dynamic RNA Modifications in Beta Cells in Type 1 Diabetes Major goals: This project will investigate the alterations in RNA marks in islets and how they impact islet biology and function. 2019-2021 PI 1 UO1 DK123717-01 Title: One-compound, one-islet: A high-throughput platform for small-molecule discovery. Major Goals: This proposal will focus on a screening approach that will use one compound for each islet to explore their effects on islet function and growth. 2017-2020 Co-PI 1 UC4 DK116255-01 Title: Development of small molecule-based methods for targeted cargo delivery to beta cells Major goals: In this project we will explore the ability of small molecules to be targeted to the beta cell to enhance its proliferation in mouse and human islet models. 2014-2019 PI NIH 1RO1 DK103215-01 (NCE) Title: Role of SerpinB1 in beta-cell growth Major goals: Investigate and characterize the role of a liver-derived beta cell growth factor in human and mouse beta cell proliferation and survival. 2018-2019 Co-I R41 DK115326-01A1 (NCE) Title” Regulation of autoimmune type 1 diabetes by serpins B1 and A1 (alpha-1antitrypsin) Major goals: Evaluate the ability of exogenous serpins to modulate glycemia in a type 1 diabetes model. 2016-2020 PI JDRF Grant Title: Role of cannabinoid receptors in human islets Major goals: To investigate the ability of Cannabinoids to modulate beta cell proliferation and survival. 2017-2019 PI JDRF Innovative Grant Title: Development of methods to target beta cell proliferation. Major goals: Develop gene editing approaches to targeting beta cell proliferation in vivo. 2017-2019 PI JDRF Grant Title: Effect of stressors on beta cell resistance in a model of T1D

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Major goals: Evaluate the effects exogenous stressors on beta cell survival and proliferation in a model of T1D. 2018-2019 PI Frequency Therapeutics Title: Significance of intestinal stem cells for beta cell regeneration Major goals: Examine the ability of intestinal stem-cell derived beta cells in regulating glycemia. 2019-2021 PI Beatson Foundation Title: Evaluating the therapeutic significance of serpinB1 in T1D – a proof-of-concept proposal Major Goals: Examine the impact of a protease inhibitor in modulating the progression of T1D in NOD mice. 2020-2022 (pending) PI JDRF Grant Report of Local Teaching and Training Teaching of Students in Courses Prior to Harvard Appointment 1987-1989 Animal and Human Physiology, St. John’s Medical College, Bangalore

1st, 2nd Year Medical Students (60), Nursing Students (30), Laboratory Technicians (10) Tutor 8-hr sessions/week, 16 weeks/year

1990-1991 Animal and Human Physiology, St. John’s Medical College, Bangalore 1st, 2nd Year Medical Students (60) Lecturer 3-hr sessions/week, 16 weeks/year

1995-1996 Endocrinology, Hammersmith Hospital, London Internal Medicine Diploma Students (14) & Medical Residents (8) Lecturer 2-hr sessions/week, 4 weeks/year

During Harvard Appointment 2004- Biology 300 (Quarter Course), Biological and Biomedical Sciences (BBS), Harvard PhD Students (6-10) Faculty Member 2-hr sessions/week, 8 weeks (2 hrs preparation time/session) These Courses included didactic sessions and discussions of scientific manuscripts focused on signaling pathways in the endocrine pancreas, with a focus on the normal regulation of glucose homeostasis. The Courses also included sessions that addressed alterations in signaling pathways in pathophysiological states such as diabetes and obesity. I lectured in 2 of the classes. For the remainder of the Course, I led and moderated discussions by each of the students who presented scientific manuscripts to the class. Fall semester Medical Sciences 302, Conduct of Science Ethics, BBS, Harvard 2014- Second-year graduate students (8-10) Faculty Discussion Leader (Course Director: Prof. Raju Kucherlapati, MD, PhD) 1.5-2-hr sessions, 3 times/year (2 hrs preparation time/session)

Through presentations, source materials and discussions, I will address the mores of scholarship and responsible practices for conducting research.

Laboratory and Other Research Supervisory and Training Responsibilities 1991-1996 Cell Culture, Receptor-ligand interactions and peptide assays, Francis Fraser Labs, London

PhD Research Students (14) 6-8 hrs per week

1998-2000 Cell culture, Animal physiology and hormone assays, Joslin Diabetes Center, Boston Research Assistants (6, most of whom pursued graduate-level education)

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6-8 hrs/week 2000- Weekly meetings with post-doctoral fellows, research assistants, graduate students: as needed, mentoring of research design; troubleshooting research problems; mentoring grant and manuscript writing; mentoring how to review manuscripts; writing Fellowship applications, advanced postdoctoral fellowship applications, junior faculty position applications 30-minute meetings with each individual; total weekly effort: ~6-8 hours 2004 - Weekly meetings with summer students, interns, visiting scientists: as needed, mentoring of research design; troubleshooting research problems; mentoring grant and manuscript writing; mentoring how to review manuscripts 30-minute meetings with each individual; total weekly effort: ~6-8 hours Formally Supervised Trainees (This section includes selected papers and presentations.) 2000-2001 Sarah N. Flier, MD Current Position: Instructor, HMS; Gastroenterologist, Beth Israel Deaconess Medical Center, Boston 2000-2002 H. Joseph Goren, PhD Current Position: Professor of Biochemistry, University of Alberta Medical School, Calgary, Canada 2001-2006 Terumasa Okada, MD, PhD Current Position: Chief Endocrinology and Metabolism, Nagarayama Sogi Hospital, Chiba, Japan First author: Proc Natl Aca Sci USA 104:8977-8982, 2007 Co-author: Nat Genetics 38(5):583-588, 2006; Diabetes 56:311-319, 2007; PLoS One 4(11): e7983, 2009; PLoS One 6(11): e28050, 2011 2002-2004 Umut Ozcan, MD Current Position: Associate Professor, Pediatrics, HMS; Associate in Medicine, Boston Children’s Hospital 2004-2005 Fausto Hegardt, PhD Current Position: Professor of Biochemistry, University of Barcelona School of Pharmacy, Barcelona, Spain 2004-2008 Siming Liu, PhD Current Position: Research Associate, University of California, Davis, CA First author: PLoS One 4(11): e7983, 2009 2005-2006 Nicole Neubauer, PhD Current Position: Application Specialist Affymetrix, London, UK Co-author: J Clin Invest 117(11):3463-3474, 2007 2005-2008 Tomoaki Morioka, MD, PhD Current Position: Lecturer, University of Osaka City, Osaka, Japan First author: US Endocrine Disease 1: 42-44, 2006; J Clin Invest 117(10):2860-2868, 2007; Mol Endocrinol 26(6):967-976, 2012 2005-2009 Anke Aßmann, MD, PhD Current Position: Fellow in Endocrinology, Charité University Medical School, Berlin First author: Mol Cell Biol 29(11):3219-28, 2009; Ped Diabetes, 10(1):14-32, 2009;

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Co-author: PLoS One 4(11): e7983, 2009; Proc Natl Acad Sci USA 111(22):E2319-28, 2014

2005- 2012 Chong Wee Liew PhD Current Position: Assistant Professor, University of Illinois, Chicago; K99/R00 NIH Award

First author: Diabetes Obes Metab 11 (Suppl. 4): 21–9, 2009; J Clin Invest 120(8):2876- 2888, 2010; Nature Medicine 19(2):217-226, 2013; Proc Natl Acad Sci USA 111(22): E2319-28, 2014

Co-author: Proc Natl Aca Sci USA 104:8977-8982, 2007; Cell Metabolism 9:350-361, 2009; PLoS One 4(11): e7983, 2009; Diabetes 60(4):1210-22, 2011; PLoS One 6(11): e28050, 2011; Mol Endocrinol 26(6):967-976, 2012; Cell Reports 3(2):401-410, 2013; Diabetes 62:2439-2449, 2013; Proc Natl Acad Sci USA 111(3):1192-1197, 2014; Cell Metabolism 22:239-252, 2015; J Proteom Res 14:3111-3122, 2015; Cell Metabolism 22:239-252, 2015; Diabetologia 60(8):1442-1453, 2017

2006-2008 Charlotte Hinault, PhD Current Position: Associate Professor, INSERM, Nice, France

First author: Diabet Obes Metab 10 Suppl. 4:136-46. 2008; Diabetes 60(4):1210-22, 2011; Diabetes 59(4):987-996, 2010

Co-author: J Proteome Res 7(8):3114-26, 2008 2006-2010 Dan Kawamori MD PhD Current Position: Assistant Professor, Osaka University First author: Cell Metabolism 9:350-361, 2009; Islets 1(3):276-279, 2009; Adv Experimental Medicine & Biology 654:421-445, 2010; Diabetologia 60(8):1442-1453,2017 Co-author: J Clin Invest 117(11):3463-3474, 2007; Diabetes 59(4):987-996, 2010; J Clin Invest 120(8):2876-2888, 2010; Diabetes 60(4):1210-22, 2011; Endocrinology 153(10):4593-4599, 2012; Nature Medicine 19(2):217-226, 2013; Cell Reports 3(2):401- 410, 2013; Diabetes 63(1):188-202, 2014; Proc Natl Acad Sci USA 111(22):E2319-28, 2014 2007-2008 Judy Shih, MD, PhD Current Position: Clinical Research Fellow, Children’s

Hospital, Boston Co-author: Cell Metabolism 9:350-361, 2009

2007-2010 Hannah Welters PhD Current Position: Lecturer, University of Plymouth, UK First-author: Trends Endocrinol Metab 19(10):349-55, 2008; Endocrinology 153(10):4593-4599, 2012 2009-2010 Susana Silva PhD Current Position: Post-Doctoral Fellow, Portugal. 2009-2010 Ingvild Aukrust PhD Fellowship from Norway; Current position: Research Scientist, University of Bergen, Norway First author: J Biol Chem 288:5951-62, 2013 Co-author: Mol Cell Endocrinol 382(1):55-65, 2014 2009- Ercument Dirice PhD Current position: Assistant Professor, NYMC ; Senior Advanced

Post-doctoral JDRF Fellowship First author: book chapter in Islet Growth Factors, pp 1-22, 2011; Diabetes 63(1):188- 202, 2014; J Invest Med 64(1):14-20, 2016; J Biol Chem 292(43):17598-17608, 2017.

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Co-author: Cell Reports 3(2):401-410, 2013; J Biol Chem 288:5353-5356, 2013; Proc Natl Acad Sci USA 111(3):1192-1197, 2014; Stem Cell Rep 3:5-14, 2014; Cell Metabolism 22:239-252, 2015; J Proteom Res 14:3111-3122, 2015; Diabetes 65(5):1208-1218, 2016; Diabetes 65(6):1660-1671, 2016; JCI Insight 2019; Nat Metabolism (2019)

2010-2011 Helge Raeder MD Fulbright Fellowship from Norway; Current Position: Professor of Pediatrics, University of Bergen, Norway First author: Diabetes 63(1):259-269, 2014 Co-author: J Biol Chem 288:5353-5356, 2013 2010-2013 Masaru Akiyama MD Current Position: Assistant Professor, Yamaguchi University, Japan First author: Diabetes 62:2439-2449, 2013 Co-author: Adv Experimental Medicine & Biology 654:421-445, 2010 2010-2014 Shweta Bhatt PhD Current Position: Post-Doctoral Fellow, New Delhi, India

First author: Book chapter in Translational Endocrinology of Bone: Reproduction, Metabolism, and the Central Nervous System, pp. 199-220, 2012; Cell Metabolism 22:239-252, 2015. Co-author: Diabetes 63(1):259-269, 2014; J Proteom Res 14:3111-3122, 2015.

2010-2017 Abdelfattah El Ouaamari PhD Current Position: Assistant Professor, Rutgers Univ, NJ;

First author: Cell Reports 3(2):401-410, 2013; J Proteom Res 14(8):3111-31122, 2015;Cell Metabolism 23(1):194-205, 2016; Co-author: Endocrinology 153(10):4593-4599, 2012; Diabetes 63(1):259-269, 2014; Diabetes 63(1):188-202, 2014; Mol Metabolism 3(8):794-802, 2014; Cell Metabolism 22:239-252, 2015; PLoS One 11(2):e0148252, 2016; Diabetes 65(8):2201-2213, 2016; Cell Metabolism 25(4): 868-882, 2017

2011-2012 Geir Helgeland MD Current position: Post-Doctoral Fellow, University of Bergen, Norway 2011-2014 Adrian Teo PhD JDRF Fellowship; Current Position: Junior Investigator,

Institute of Molecular and Cellular Biology (IMCB); Adjunct Assistant Professor, School of Biological Sciences (SBS), Nanyang Technological University (NTU), Singapore

First author: EMBO J 31(20):3956-3957, 2012; J Biol Chem 288:5353-5356, 2013; Cell Metabolism 18(6): 775-791, 2013; Stem Cell Rep 3:5-14, 2014; Science Trans Med 7(273):273ps2, 2015; Mol Metabolism 4(9):593-604, 2015; Stem Cell Rep 6(30:357-367, 2016

Co-author: Diabetes 63(1):188-202, 2014; Stem Cells Translational Medicine Aug 7, 2015 2011- Manoj Gupta PhD Current Position: Post-Doctoral Fellow, Joslin Diabetes Center Presentation: International Society for Stem Cell Research (ISSCR) Meeting, 2014 Co-author: . Stem Cell Res 14(3):307-322, 2015 Mol Metabolism 4(9):593-604, 2015

First author: Stem Cells Translational Medicine 4(10):1101-1108, 2015; Cell Metabolism 22:239-252, 2015

2011-2016 Ivan Valdez Current position: BBS Graduate Student, HMS; NIH F31 Fellowship

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Co-author: Stem Cell Rep 3:5-14, 2014; Cell Metabolism 22:239-252, 2015; First author: Science Trans Med 7(273):273ps2, 2015; Cell Reports 15(3):460-470, 2016.

2012-2013 Kazuyoshi Tomita PhD Current Position: Research Scientist, Shinogi and Co., Ltd., Japan 2012-2013 Teresa Mezza MD Current Position: Resident in Endocrinology, Università del

Sacro Cuore (Catholic University of the Sacred Heart), Policlinico Universitario Agostino Gemelli (Agostino Gemelli Teaching

Hospital), Rome, Italy First author: Diabetes 63:994-1007, 2014; Diabetologia 57(7):1291-1303, 2014; JCEM 101:470-475, 2016; J Biol Chem 2016 (in press).

2012-2013 Anders Molven PhD Fulbright Scholar, Joslin Diabetes Center; Current Position Professor of Pathology, University of Bergen, Norway First author: Diabetes 65(6):1672-1678, 2016. 2012-2015 Tomozumi Takatani MD PhD Fellowship from Japan Society for the Promotion of

Science (JSPS); Senior Iacocca Fellowship; Current Position: Assistant Professor, Chiba University School of Medicine, Chiba, Japan

Oral presentation: Emerging Concepts and Targets in Islet Biology (D3) meeting, Keystone Symposia Scientific Conferences on Biomedical and Life Science Topics, 2014 First author: Scientific Reports 6:28177, 2016 2013- Dario Ferreira De Jesus Fulbright Master’s Scholarship; Current position: Post-doctoral

Fellow, Joslin Diabetes Center Co-author: Diabetes 63(1):188-202, 2014; J Proteom Res 14:3111-3122, 2015. First author: Trends Endocrinol Metab 25(12):628-636, 2014; Nat Metabolism (2019) 2014-2017 Jun Shirakawa MD PhD Current Position: Assistant Professor, Yokohama, Japan

First author: Cell Metabolism 25(4):868-882, 2017; Diabetes Obes Metab Suppl 1:71-77, 2016Co-author: Stem Cells Translational Medicine 4(10):1101-1108, 2015; Cell Metabolism 22:239-252, 2015; J Proteom Res 14(8):3111-31122, 2015; Endocrinology 156(11):4047-4058, 2015; Cell Metabolism 23(1):194-205, 2016; Cell Reports 15(3):460-470, 2016. Scientific Reports 6:28177, 2016; Diabetologia 60(8):1442-1453, 2017

2014- Sevim Kahraman PhD Current Position: Post-Doctoral Fellow, Joslin Diabetes Center

First author: AJP Endocrinol Metab 307(10):E906-18, 2014; Curr Diab Rep 16(8):70, 2016; Co-author: Diabetes 63(1):188-202, 2014; J Proteom Res 14:3111-3122, 2015.

Oral Presentation: American Diabetes Association 72nd Scientific Sessions, 2012 (Diabetes 61: (Suppl.1) A72-73, 2012) 2015-2016 Chiara Cefalo MD Current Position: Post-Doctoral Fellow, Rome, Italy Co-author: JCEM 101:470-475, 2016 2015-2018 Erin Okawa MD Current Position: Asst. Professor, UCLA; Past T32 Fellowship First author: Curr Diab Rep 16(8):70, 2016; Co-author: Cell Metabolism 2017 2015- Giorgio Basile PhD Current Position: Post-Doctoral Fellow, Joslin Diabetes Center

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2016- 2019 Kazuki Orime MD PhD Previous Position: ost-Doctoral Fellow, Joslin Diabetes Center; Fellowship from Japan; Current Position: Asst. Professor, Department of Medicine, Yokohoma University, Japan 2017- Kimitaka Shibue MD PhD Current Position: Post-Doctoral Fellow, Joslin Diabetes; Fellowship from Japan; Helmsley Foundation 2017- Kazuki Fukuda MD PhD Current Position: Post-Doctoral Fellow, Joslin Diabetes; Fellowship from Japan 2017-2019 Johanna Ludeke MSc Current Position: PhD Student, Joslin Diabetes Center; Studentship from U Bergen, Norway 2017-2018 Yi Zhang MD Current position: Post-doctoral Fellow, Joslin Diabetes Center; Fellowship from China 2019- Hyunki Kim MD PhD Current position: Post-doctoral Fellow, Joslin Diabetes Center 2019- Ling Xiao PhD Current position: Post-doctoral Fellow, Joslin Diabetes Center 2019- Aaron Chapla MD Current position: Post-doctoral Fellow, Joslin Diabetes Center Local Invited Presentations Those presentations below sponsored by outside entities are so noted and the sponsor is identified in parentheses. 2004 The insulin/IGF axis and islet function: implications for type 2 diabetes. Endocrine Grand Rounds Mass. General Hospital, Boston, 2004 Significance of insulin/IGF-I signalling for the development of type 2 diabetes.

Research Seminar, Harvard University (Host: Doug Melton) 2005 Insulin action and insulin resistance in islets: evolving concepts in type 2 diabetes. Endocrine Grand Rounds Beth Israel Deaconess Medical Center/HMS, Boston 2005 Islet Cell Regeneration – Current Concepts. Joslin Tuesday Research Seminar Joslin Diabetes Center, Boston 2007 Beta-cell Function in Type 2 Diabetes and the Incretin System in Health and Disease. Novartis Corporate Education Program Joslin Diabetes Center, Boston (Sponsor: Novartis) 2008 Role of leptin in islet growth and function. Gastrointestinal Seminar Series, Massachusetts General Hospital, Boston 2008 Implications of leptin signalling in islets for obesity-associated diabetes. Invited Lecture, Department of Genetics and Complex Diseases, Harvard School of Public

Health, Boston 2010 Insulin resistance in beta cells. Endocrinology Preceptorship Program,

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Joslin Diabetes Center, Boston 2011 Beta-cell Preservation and Regeneration in Diabetes: Is it possible? Diabetes 2011: From

Research to Clinical Practice. Joslin Educational Program (Sponsor Novartis), Harvard Medical School, Boston

2013 Harnessing iPS cells for discovery in diabetes and metabolic disease. International Society for Stem Cell Research (ISSCR) Public Forum, Harvard Stem Cell

Institute 2016 Is promoting β-cell proliferation a realistic objective? Broad Institute Joint Seminar Series.

Nov 15, 2016 (Hosts: V. Mootha MD PhD; J. Hirschhorn MD PhD: J. Florez MD PhD) 2017 Novel concepts in β-cell regeneration. Joslin Tuesday Research Seminar, Joslin Diabetes Center, Boston Report of Regional, National and International Invited Teaching and Presentations Those presentations below sponsored by outside entities are so noted and the sponsor is identified in parentheses. Regional: 2004 Islets and insulin/IGF-I signalling: significance for type 2 diabetes. Research Seminar, Novartis, Cambridge, MA (Sponsor: Novartis) 2004 Growth factor signaling and beta-cell regeneration. Invited Speaker. Stem and Developmental Cell Group Meeting, HMS (regional attendees). 2005 Physiology and Pathophysiology of Diabetes. Joslin Symposium for Physicians (Sponsor: Eli Lilly) (regional attendees) 2005 Investigation of potential circulating factors that stimulate beta-cell proliferation. Research Seminar, Center for Engineering in Medicine Shriners Hospital, Boston 2006 Growth factor signalling and islet cell regeneration in human tissues and mouse models. Endocrine Research Seminar. U Vermont, Burlington 2007 Beta cells and their potential for regeneration in type 1 diabetes American Diabetes Association “Step Out” Event to Fight against Diabetes Seaport Hotel, Boston (Sponsor: American Diabetes Association) 2007 Insulin resistance in beta cells: is type 2 diabetes secondary to a single abnormality. Joslin Lilly Corporate Education Program, Hilton Hotel, Boston (regional attendees) 2008 Significance of insulin and leptin in islet growth: implications for obesity-associated diabetes. Tufts University, Boston 2008 Role of leptin in islet biology.

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Research Seminar, Marine Biological Laboratories, Woods Hole, MA 2009 Significance of beta cells in the prevention of type 1 diabetes (Sponsor: American Diabetes Association), Omni Parker House Hotel, Boston 2009 Insulin - a player in the regulation of alpha-cell function Endocrine Research Seminar, Division of Endocrinology, Yale University, New Haven, CT 2009 A role for the “tribbles” protein in insulin exocytosis in human islets.

Adipocyte and Metabolic Tissue Study Group Seminar, Boston Obesity Nutrition Research Center, Boston Medical Center

2010 Growth factor signalling and islet cell regeneration. Diabetes Group Seminar, Broad Institute, Cambridge (regional attendees)

2010 New frontiers in diabetes pathophysiology: metablic stress and beta-cell mass. Diabetes Lunch

and Learn Series. Web-based presentation (Sponsor Bristol-Myers-Squibb), Boston, MA 2010 Regenerating pancreatic islet cells. Invited speaker; Discovery on Target, World Trade Center,

Boston, MA 2011 Beta-cell Regeneration. Tour De Cure “Kick Off” Event to Fight against Diabetes, Danvers,

MA (Sponsor: American Diabetes Association) 2015 Approaches to enhance beta cell mass to counter progression of diabetes. Science of

Therapeutics Seminar. Broad Institute of MIT and Harvard, Cambridge, MA. (Host: B Wagner PhD).

2016 Liver regulation of beta-cell growth. Endocrine Grand Rounds. Massachusetts General

Hospital, Boston (Hosts: D. Nathan MD and J.C. Florez MD PhD) National: 2002 Insulin and IGF-I signalling in islet beta-cells—lessons from tissue-specific knockouts. Endocrine Research Seminar, Dept of Mol. Physiology and Biophysics, Nashville, TN 2002 Insulin and IGF-I signaling in the beta cell: lessons from tissue-specific knockout studies, Endocrine Seminar. Dept. of Endocrinology, University of Pittsburgh, Pittsburgh, PA 2002 Islet dysfunction in diabetes: a critical role for insulin/IGF-I signaling in the beta cells. Endocrine Grand Rounds, Baylor College of Medicine, Houston, TX 2003 Implications for dysfunctional insulin/IGF-I signalling in beta-cells for the development of type 2 diabetes. Endocrine Grand Rounds, University of Miami School of Medicine, Miami. 2003 Implications of dysfunctional insulin/IGF-I signaling in the islets for the development of type 2 diabetes.

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Seminars in Clinical Research.The Rockefeller University, New York, NY. 2003 A role for insulin signaling in beta-cell function and growth. Invited Speaker, Federation of American Societies for Experimental Biology, Summer Conference, Snowmass, CO 2003 Phenotypic and functional consequences in insulin receptor knockout animals. Symposium on ‘Diabetes Mellitus and its Complications,’ Buffalo, NY 2003 Novel insights into IGF-1 signaling in beta-cells using a knockout mouse model. Endocrine Grand Rounds. Indiana University School of Medicine, Indianapolis. 2003 The islet beta cell: a critical target for insulin/IGF-I action. Research Seminar, Eli Lilly Co., Indianapolis, IN 2003 The insulin/IGF axis and islet function: implications for diabetes. Endocrine Grand Rounds, University of Louisville, KY 2004 Islet/beta-cell growth in compensatory response to insulin resistance. Invited Speaker. BCBC Investigator Retreat, Chicago, IL 2004 Insulin resistance in pancreatic islets/beta-cells: an evolving concept. Endocrine Grand Rounds, New York, NY 2005 Insulin resistance in islet beta cells: an evolving concept in type 2 diabetes. Endocrine Grand Rounds, University of Utah Medical School, Salt Lake City, UT 2005 Insulin action and insulin resistance in islets: evolving concepts in type 2 diabetes. Medical College of Ohio, Toledo 2005 Beta cells from existing islets. Symposium Speaker. “Origins of pancreatic islets.” 87th Annual Endocrine Society Meeting, San Diego, CA 2005 Islet Cell Regeneration and Insulin/IGF-I Signaling. Research Seminar, Larry Hillblom Islet Research Center. University of California, Los Angeles 2005 Dissecting islet cell regeneration using human tissues and mouse models. Research Seminar, Division of Metabolism, Endocrinology and Diabetes (MEND), Dept. of Internal Medicine, U Michigan, Ann Arbor 2006 Islet Cell Regeneration: Insights from mouse models and human pancreatic tissues. Endocrine Grand Rounds, University of Virginia at Charlottesville 2006 A critical role for insulin signalling in beta cells during neonatal development and compensatory response to insulin resistance. Invited Speaker, Distinguished Lecture Series, Barbara Davis Center for Childhood Diabetes, U Colorado at Denver

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2006 Islet Cell Regeneration: Insights from mouse models and human pancreatic tissues. Endocrine Research Seminar, Mt. Sinai School of Medicine, New York, NY 2006 Disruption of insulin signalling impacts multiple pathways in islet beta cells. Biochemistry Seminar Series, U of Utah Medical School, Salt Lake City, Utah 2006 Current concepts in the regulation of beta-cell mass. Research Seminar, Division of Medicine, U of Alabama School of Medicine, Birmingham 2007 Role of insulin receptors in compensatory beta-cell growth response to insulin resistance. Institute for Diabetes, Obesity, and Metabolism Seminar. U Penn, Philadelphia 2007 Insulin Signaling and Islet Cell Proliferation Invited Speaker. Mathematical Biosciences Institute’s Workshop on “Endocrine Physiology: Type 2 diabetes, metabolism and obesity”, Ohio State University, Columbus 2007 Current concepts in the maintenance of beta-cell mass. Research Seminar, Indiana University School of Medicine, Indianapolis 2007 Significance of insulin/leptin signalling in islet biology: implications for obesity- associated diabetes. Frontiers in Pharmacology Seminar. New York University, NY 2008 Role of insulin and leptin signalling in islets – implications for type 2 diabetes and obesity-associated diabetes. Biochemistry Colloquium Series, Univ of Madison, Wisconsin (Host: Alan Attie, PhD) 2008 Recent concepts in beta-cell regeneration. Endocrine Research Seminar, Mayo Clinic, Rochester MN 2008 Role of intra-islet insulin in the regulation of alpha-cell function and hypoglycemia. Endocrine Grand Rounds, University of California, San Diego,Veterans Hospital 2008 Glucose effects on beta cells require activation of insulin receptors and insulin receptor substrate-2. San Diego Beta Cell Society Meeting, San Diego, CA 2008 Insulin action in beta and alpha cells regulates pancreatic islet function. Research Seminar, Washington University, St. Louis, MO 2009 Growth factor signalling and the regulation of beta-cell growth and function. Endocrine Grand Rounds, Eli Lilly Co., Indianapolis, Indiana (Sponsor: Eli Lilly) 2009 The central role of beta cells in the prevention of type 2 diabetes. Takeda Visiting Scholar Lecture, Takeda, Chicago, IL (Sponsor: Takeda) 2009 A novel role for the tribbles protein in insulin exocytosis in human islets. Metabolism Forum, Stedman Auditorium, Center for Living Campus

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Duke University Medical Center, Durham, NC (Host: Chris Newgard, PhD) 2010 Search for circulating beta-cell growth factors in mouse models of insulin resistance Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA (Host: W. Qian, PhD) 2010 IRS/1 and IRS-2 signaling in beta-cell regeneration. JDRF-Sanofi-Broad Workshop on beta-

cell replication, Broad Institute, Cambridge MA (national attendees) 2010 The role of the tribbles protein in insulin exocytosis in human β-cells. Cardiovascular and

Metabolism Beta-Cell Initiative Seminar Series, Novartis, Cambridge, Boston, MA 2010 Significance of insulin and leptin in islet biology: implications for obesity-associated diabetes

and heart disease. Sentara Hospital Cardiology Grand Rounds, Eastern Virginia Medical School, Endocrine Society Visiting Professorship in Endogenous Pancreas Preservation, Norfolk, VA . (Host: Jerry Nadler, MD)

2010 Beta-cell function in type 2 diabetes and the incretin system in heath and disease. Internal

Medicine Grand Rounds, Eastern Virginia Medical School, Endocrine Society Visiting Professorship in Endogenous Pancreas Preservation, Norfolk, VA. (Host: Jerry Nadler, MD)

2010 The insulin/insulin-like growth factor axis and islet function: implications for type 2 diabetes.

Endocrine Grand Rounds, Eastern Virginia Medical School, Endocrine Society Visiting Professorship in Endogenous Pancreas Preservation, Norfolk, VA. (Host: Jerry Nadler, MD)

2011 Growth factor signaling and the regulation of proinsulin processing, and endoplasmic

reticulum stress in pancreatic beta cells. Invited Speaker, Biochemistry Seminar Series. San Antonio School of Medicine, San Antonio, TX. (Host: F. Folli, MD)

2011 Examples of bench to bedside and back to bench research. MD-PhD Program. San Antonio

School of Medicine, San Antonio, TX (Host: F. Folli, MD) 2011 Beneficial effects of alogliptin/pioglitazone therapy in a mouse model of type 2 diabetes.

SMART Takeda Visiting Scholar Lecture, Takeda, Chicago (Sponsor: Takeda) 2011 Insulin action in beta cells – effects on proinsulin processing. Endocrine Grand Rounds,

Indiana University School of Medicine, Indianapolis (Host R. Mirmira MD PhD) 2011 Liver-derived islet beta-cell growth factors. Sanofi Aventis Advisory Board Meeting, Miami,

FL (Sponsor: Sanofi Aventis) 2012 Growth factor signaling in pancreatic islets. Division of Metabolism, Endocrinology &

Diabetes Seminar. University of Michigan, Ann Arbor (Host: E. Bernal-Mizrachi MD) 2012 Insulin modulates proinsulin processing by regulating translation initiation in pancreatic beta

cells. Endocrinology Seminar. Northwestern University, Chicago, IL (Hosts: F. Mauvais-Jarvis MD PhD; J. Bass MD)

2012 Growth factor signaling and the regulation of beta-cell biology. Endocrine Grand Rounds.

Univ. Maryland, Baltimore. (Host: AR Shuldiner MD; Sponsor: Merck)

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2013 Trip-Br2 and adipocytes. Endocrine Grand Rounds. Department of Endocrinology and

Metabolism. Cleveland Clinic, Cleveland, OH (Host: Leila Khan MD). 2013 Approaches to regenerate beta cells to counter diabetes. Endocrine Grand Rounds University

of Iowa School of Medicine, Iowa City (Host: E. Dale Abel MD) 2013 Investigating regeneration of beta cells in type 1 diabetes. Endocrine Grand Rounds. State

University of New York, Downstate, Brooklyn, NY (Host: MA Banerji MD). 2014 Induced pluripotent stem cells: role in diabetes James H. Horner Distinguished Visiting Professorship, University of Tennessee Health Science Center, Memphis, TN. (Host: S. Dagogo- Jack, MD) 2014 Growth factor signalling in the regulation of the endocrine pancreas. Seminar in the Department

of Genetics and Development. Columbia University, New York, NY (Host: G. Karsenty MD) 2014 Role of insulin/insulin like growth factor signalling in the regulation of pancreatic islet cells.

Seminar at Diabetes and Obesity Research Institute, Univ Southern California (Host: B. Stiles PhD).

2015 Interrogating beta cell proliferation in type 1 diabetes. Seminar at Children’s Hospital, University

of Pittsburgh. (Host: G. Gittes MD) 2015 Invited Panelist. Symposium on “Translational Research in a Clinical Career: Fostering Diabetes

Translational Physicians and Researchers”. 75th Annual Meeting of the American Diabetes Association. June 4-7, 2015, Boston MA.

2015 Approaches to enhance beta cell mass. Annual Symposium on “Beta cell replacement”.

University of Washington, Seattle. (Host: R. Hull PhD; Sponsor Sanofi) 2015 Invited speaker. Symposium on “Towards curing diabetes with stem cell derived products”.

Mayo Clinic, Minnesota. (Host: Y. Kudva MD) 2015 Keynote Speaker. Diabetes and Obesity Research Day. “Approaches to enhance functional beta

cell mass to counter diabetes”. University of Illinois at Chicago, Chicago. (Host: T. Unterman MD)

2015 Invited speaker. Barshop Symposium on Aging: “Metabolism and Aging: From Molecular

Physiology to Systems Biology”. The Mayan Ranch, Bandera, Texas. (Host: N. Musi MD), 2015 Keynote Speaker. Rising Star Symposium. University of Utah School of Medicine, Utah. (Host:

S. Fisher MD PhD). 2015 Growth factor signaling and islet cell proliferation and function. DRTC Seminar at Vanderbilt

University of Medicine, Nashville, Tennessee. (Host: M. Gannon PhD). 2016 Hepatic Regulation of islet cell growth. Endocrine Grand Rounds. NYU, New York. (Host: I.

Goldberg MD).

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2016 Using iPS cells to interrogate complications in type 1 diabetes. Research Seminar. NYU Langone Research Center. NY. (Host: I. Goldberg MD).

2016 Liver regulation of islet growth. Endocrine Grand Rounds. Diabetes Center Lecture, Johns

Hopkins School of Medicine, Baltimore, Maryland (Host: M. Hussain MD). 2016 Growth factor signalling in islet β-cells. Work in Progress Seminar Series, Diabetes Obesity and

Metabolism Institute, Icahn School of Medicine, Mount Sinai, NY (Host: A. Stewart MD). 2016 Keynote Speaker. Novel factors regulating human beta cell proliferation. UAB Diabetes

Research Day. University of Alabama at Birmingham. (Host: A. Shalev MD). 2017 Harlan G. Wood Memorial Annual Lecture. Lessons in pancreatic islet biology learned from

growth factor signalling. Dept. of Biochemistry, Case Western Reserve University, Cleveland (Hosts: N. Rege; M. Weiss MD PhD)

2017 Relevance of growth factor signalling in regulating islet beta cell mass. UTHSCSA Diabetes

Research Center Seminar Series. San Antonio, TX (Host: R. Defronzo MD). 2017 Role of Growth Factors (Insulin and IGF-1) in Stem Cell Renewal and Differentiation. Mayo

Clinic Regenerative Diabetes Program. Rochester, MN (Host: Yogish Kudva MD) 2017 Pancreatic beta cell regeneration – role for endogenous growth factors. Pancreas Regeneration

Symposium. New York, NY (Host: Michael Franti PhD) 2018 Update on growth factor regulation of islet biology. IBRI/Indiana University Center for Diabetes

and Metabolic Diseases Seminar, Indianapolis (Host: T Mastracci PhD/R, Mirmira MD PhD) 2018 Growth factor signalling in the regulation of islet biology. Endocrine Seminar, Vanderbilt

University 2018 Harnessing the zinc content in beta cells for targeting to regenerate beta cells. HIRN Annual

Meeting, Washington DC. 2018 Importance of insulin signalling in humans and mice in regulating beta cell function. University

of Miami, Endocrine Seminar (Host: E. Bernal-Mizrachi MD) International: Please note: In addition to delivering many international talks, including visiting professorships, keynote addresses, and named lectures, I have chaired sessions at numerous international meetings on diabetes and obesity in the US, Europe and Japan. 1990 Work performance and chronic under nutrition.

Research Seminar on Nutrition and Work Performance, Dept. of Human Nutrition, University of Southampton, Southampton, UK.

1990 Amylin and insulin in an in vitro beta-cell model. Research Seminar, Biochemistry, Genetics and Development Groups, Division of Biological Sciences, University of Sussex at Brighton, UK.

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1999 Can insulin resistance of the pancreatic beta cell cause diabetes?

Invited speaker, Biannual Meeting Finnish Diabetes Research Foundation, Tampere, Finland.

1999 Implications of dysfunctional insulin signaling in the pancreatic beta cell. Invited Speaker at International Meeting, Japanese Society for Diabetic Complications, Otsu, Japan. 1999 Role of insulin signaling in the endocrine pancreas. Research Seminar, Wakayama University of Medical Science, Wakayama, Japan. 1999 Contrasting results from insulin receptor knockout models in mice – lessons in type 2 diabetes. Invited speaker at Symposium on New Insights in Diabetes Research – Turn of the Millenium. Shiga University of Medical Science, Shiga, Japan. 2001 Lessons from liver and beta-cell-specific insulin receptor knockout and double knockout studies. Invited speaker at Symposium on New insights into the role of the liver in type 2 diabetes, Hagedorn Research Institute, Gentofte, Denmark. 2001 Role of insulin- and IGF-1-receptors in islet function. Invited speaker at Symposium on “Islets and type 2 diabetes”. The Biochemical Society, Bristol, UK. 2001 Lessons in islet function from gene knockout studies. Endocrine Research Seminar, MRC Clinical Sciences Center, Imperial College School of Medicine, Hammersmith Hospital, London, UK. 2001 Search for islet growth factors in animal models of insulin resistance. Research Seminar, AstraZeneca, Alderley Park, Macclesfield, UK. 2003 Insulin signaling is important in beta-cell function. Symposium on Current Issues. ADA Meeting, New Orleans, LA (international attendees) 2004 Role of insulin/IGF-1 receptors in beta-cell survival. Invited Speaker, 1st Russell Berrie International Diabetes Symposium, Jerusalem, Israel. 2005 A critical role for insulin signaling in the compensatory islet growth response to insulin resistance. Speaker at Symposium on “New Frontiers in Pancreatic Beta-Cell Research”. Japan Diabetes Society, Kobe 2005 Insulin signalling and pancreatic islet growth. Research Seminar. Ross University School of Medicine, Dominica, West Indies 2005 Islet Cell Regeneration and Degeneration – current concepts. Invited Speaker, International conference on Obesity, Diabetes and Aging: From Insulin Secretion to Insulin Action. Geneva, Switzerland

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2006 Growth factor signalling and islet cell regeneration. Endocrine Seminar, Banting and Best Center for Diabetes, Toronto, Canada 2007 Signaling pathways regulating islet cell growth and function 42nd Annual Japan Insulin Action Study Group Meeting. Tokyo, Japan 2007 Integrating Insulin and Leptin Signaling Pathways Regulating Islet Biology – Implications for Obesity-Associated Diabetes Endocrine Grand Rounds, Juntendo University, Tokyo, Japan 2007 Signaling Pathways Regulating Islet Growth. Endocrine Grand Rounds, Kawasaki University Medical School, Kawasaki, Japan 2008 Leptin and insulin signalling in islets: therapeutic implications for type 2 and obesity- associated diabetes. Research Seminar, Astra Zeneca, Alderley Park, Macclesfield, England, March 2008 2008 Regulation of pancreatic beta-cell differentiation, growth and regeneration. Invited Keynote Speaker, Japan 51st Annual Meeting of Japan Diabetes Society. Tokyo 2008 Significance of TRB3 polymorphisms on islet function and development of type 2 diabetes. Gunma University, Gunma, Japan 2008 Recent advances in regeneration of beta cells. Osaka City University, Osaka, Japan 2008 Lessons in human diabetes learned from genetically engineered mouse models: Genes affecting beta-cell function, Invited Speaker and Symposium Chair. 68th Annual Meeting of the ADA: “Overview of Insulin/IGF-1 Signaling in Islets,” San Francisco, CA (international attendees) 2008 A role for the tribbles protein (TRB3) in pancreatic beta cells. Research Seminar, McGill University, Montreal, Canada 2009 Polymorphisms in tribbles protein and human type 2 diabetes Beta Cell Advisory Group Meeting, Takeda Pharmaceuticals, Tokyo, Japan (Sponsor: Takeda) 2009 Regulation of beta-cell turnover - an update. Invited Speaker, 10th Anniversary Servier/International Group on Insulin Secretion Symposium. A decade of islet research-implications for understanding & treating type 2 diabetes. St. Jean Cap Ferrat, Nice, France (Host: Erol Cerasi MD) 2009 Islet-specific knockouts in diabetes research.

Invited Speaker, Genotypes and phenotypes of diabetes, 44th Annual European Association for the Study of Diabetes/Study Group on Genetics of Diabetes (EASD-SGGD) \meeting on genetics of diabetes. Bergen, Norway (Host: Pal Njolstad MD PhD)

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2009 Insulin signalling in alpha cells modulates glucagon secretion in vivo

Research Seminar Dept. of Molecular Medicine, St John’s Research Institute, Bangalore (Host T.S. Sridhar)

2009 A role for the tribbles protein in islet dysfunction

Merck-Frosst Lecturer, Diabetes Research Program, Child and Family Research Institute, University of British Columbia, Vancouver, Canada (Sponsor: Merck-Frosst) (Host: C. Bruce Verchere)

2009 Insulin signalling in alpha cells modulates glucagon secretion

Merck-Frosst Distinguished Speaker, Endocrine Rounds, Vancouver General Hospital, Vancouver (Sponsor: Merck-Frosst) (Host: C. Bruce Verchere)

2010 Role of insulin signalling in the regulation of proinsulin processing and endoplasmic reticulum

stress in beta cells. Endocrine Grand Rounds. Lund University Medical School, Malmo Diabetes Center, Sweden (Host: Leif Groop)

2010 Growth factor signalling in the Regulation of Endoplasmic Reticulum Stress and

Mitochondrial Function in beta cells Invited Speaker, Symposium on Regulation of pancreatic beta cell mass, International Congress of Endocrinology 2010, Kyoto, Japan 2010 Role for GLP-1 in beta cell proliferation

Endocrinology and Metabolism Seminar, Yamaguchi Graduate School of Medicine, Yamaguchi University, Ube, Japan (Host: Yukio Tanizawa)

2010 Leptin effects on beta cells: role in glucose homeostasis. Kyoto University, Kyoto, Japan

(Sponsor: Novartis) 2010 Targeting the cell cycle for beta cell regeneration. Takeda Research Labs, Osaka, Japan

(Sponsor: Takeda) 2010 A unifying hypothesis for treating both insulin resistance and beta-cell defects in type 2

diabetes. Oration, DESERT 2010 Meeting, Diabetes Society, Bangalore, India (Host: S.R Aravind)

2010 Recent advances in beta-cell research move us closer to curing diabetes. DESERT 2010

Meeting, Diabetes Society, Bangalore, India (Host: S.R Aravind) 2010 Forefront of beta cell research: Pathogenesis and mechanism of beta cell failure Invited speaker: 53rd Japan Diabetes Society Meeting, Okayama, Japan 2010 Beta cell failure: The key to unlocking type 2 diabetes mellitus

Invited Speaker. 69th Annual Meeting of the ADA. “TRB3 mutations cause type 2 diabetes by impairing insulin secretion.” Orlando, FL (international attendees)

2010 Genetic disruption of signaling proteins relevant for islet cell regeneration and function. Invite

speaker. EASD Meeting, Islet Study Group, Tallberg, Stockholm

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2010 Significance of cross-talk between the alpha and beta cells in the islets of Langerhans Institute of Metabolic Physiology Heinrich-Heine University, Dusseldorf, Germany (Host: Eckhard Lammert PhD)

2010 Growth factor signalling and islet cell proliferation. Sanofi-Aventis, Frankfurt, Germany (Sponsor: Sanofi-Aventis; Uli Stilz PhD) 2010 Genetic and translational approaches to exploring islet biology. Institute for Genetics Cologne, Germany (Host: Jens Bruning MD) 2010 Insulin signalling in alpha cells regulates glucagon secretion in vivo. IR10, XI International

Symposium on Insulin Receptor and Insulin Action Invited speaker; Naples, Italy 2010 Translational approaches to exploring islet biology. Keynote Speaker, 5th Annual Canadian

Meeting on Islet /Beta Cell Biology, Toronto (Sponsor- Merck) (Host: Dan Drucker) 2010 Insulin signalling in alpha and beta cells. Invited speaker; Diabetes Dialog, Paris, France (Sponsor: Novo Nordisk) (Host: Pierre DeMeyts MD) 2010 Genetic and translational approaches to exploring islet biology. Invited speaker. Symposium on Glucose homeostasis. 22nd Annual Conference of the

Physiological Society of India and 2nd Biennial Conference of SAAP, Bangalore. 2011 The effects of obesity and mitochondrial dysfunction on beta-cell biology.

3rd Beta Cell Advisory Group Meeting, Takeda Pharmaceuticals, Yokohoma, Japan, (Sponsor: Takeda)

2011 Tribbles homologue-3 signaling and beta-cell proliferation, cell death and function. Invited Speaker. Advances in Diabetes Research. 11th Annual Rachmiel Levine Diabetes and Obesity Symposium. Pasadena, CA

2011 Role of insulin signalling in alpha-cell fate.

Invited Speaker 12th Anniversary Servier/IGIS Symposium.pancreatic α-cells and glucagon – neglected metabolic actors. St. Jean Cap Ferrat, Nice, France (Host: E. Cerasi MD)

2011 Insulin Signaling, proinsulin processing and endoplasmic reticulum stress in beta-cells.

University of Bremen, Germany (Host: K Maedler PhD) 2011 Significance of alpha and beta cells in glucose homeostasis. Invited Speaker. Argentinian Society for Diabetes, Buenos Aires, Argentina (Host: LE Litwak

MD) 2011 Insulin regulation of beta-cell function – effects on proinsulin processing. Invited speaker

International Conference on Diabetes and Metabolism, Seoul, South Korea (Host: Hye-Seung Jung MD)

2011 Insulin regulation of proinsulin processing in pancreatic beta cells. Universitat Autonoma de

Barcelona, Bellaterra, Spain (Host: F. Bosch PhD)

29

2011 TRIP-Br2 – a novel regulator of adipocyte biology. Department Biologia e Ambiente,

Universidade de Tras-os-Montes e Alto Douro (UTAD), Vila Real, Portugal (Host: Amelia L.M. Dias da Silva)

2011 Insulin action in beta cells – an evolving paradigm. Translational Medicine – Symposium

Invited Speaker. DEBATE 2012, Le Meridien, Bangalore (Organizer and sponsor: PRIMER) (Host: SR Aravind)

2012 Reversing beta-cell function – pipe dreams to pipe lines. Plenary Session Invited Speaker. DEBATE 2012, Le Meridien, Bangalore (Organizer and

sponsor: PRIMER) (Host: SR Aravind) 2012 The role of inflammation in diabetes and obesity. 4th Beta Cell Advisory Group Meeting, Takeda Pharmaceuticals, Shanghai, China (Sponsor:

Takeda) 2012 Genes controlling islet function and proliferation.

Invited Speaker. Joint Keystone Symposia on Genetic & Molecular Basis of Obesity and Body Weight Regulation/Emerging Molecular Mechanisms for the Pathogenesis of Diabetes, Santa Fe, New Mexico. (Hosts: A. Attie, C. Newgard, P. Scherer) (International attendees)

2012 Islet beta-cell regeneration in diabetes. Invited Speaker. Society for Experimental Biology and Medicine Symposium on Stem Cell Biology 2012: Basic Science and Translational Advances. San Diego. (Host: Martin J. Adamo PhD; Michael J. Friedlander PhD)

2012 International Forum for the Advancement of Diabetes Research and Care. Multi-level

approach for successful management of type 1 diabetes. Paris, France. (Host: J. Skyler MD) 2012 Diabetes Global Therapeutic Expert Forum. Discussion Group 2: Fatty acid receptors – beta

cells and gut. Baltimore, MD (Hosts: H Katzeff PhD; G. Gustafson PhD) 2012 Physiology 2012. Symposium on ‘Can we treat obesity?’ Potential mechanisms that link

diabetes with obesity. The Physiological Society Meeting, Edinburgh, Scotland (Host: K. Murphy PhD)

2013 Insulin and ER signaling pathways in the regulation of pancreatic alpha cell biology. Beta Cell

Workshop, Kyoto, Japan. April 2013 (Host: S. Seino MD PhD) 2013 Proliferation of beta cells in non-obese diabetic model of type 1 diabetes, Seminars in

Endocrinology. Univ. of Osaka, Japan (Host: H Kaneto MD PhD) 2013 TRIP-Br2: a new player in the regulation of adipocyte biology. Seminars in Endocrinology.

Univ. of Tokyo, Japan (Host: K Ueki MD PhD) 2013 Role for TRIP-Br2 in adipocyte biology. Endocrine Seminar. Division of Endocrinology and

Metabolism. Imperial College of Medicine, London England. (Host: Sir SR Bloom FRS).

30

2013 Frontiers in Diabetes Research. Novel insights into insulin action in islets. Samuel Lunenfield Research Institute, Mount Sinai Hospital, Toronto, Canada (Hosts: Bernie Zinman MD; Dan Drucker MD PhD)

2013 Identifying novel beta-cell growth factors. New discoveries on the roles of environment and

genetics in insulin action. Joslin International Symposium on Diabetes. Oct 2013, Boston 2013 Islet growth in models of insulin resistance. XII International Symposium on insulin

receptors and insulin action: new opportunities for the prevention and treatment of diabetes in the XXI century. Barcelona, Spain (Host: FM Bosch PhD)

2013 Novel insights into islet biology. International Diabetes Federation (IDF) World Diabetes

Congress. Melbourne, Australia (Host: M Cooper MD) 2013 Inter-organ cross talk in the regulation of beta cell mass. 13th Congress of the Immunology of

Diabetes Society. Lorne, Melbourne, Australia (Host: T Kay PhD). 2013 Using induced pluripotent stem cells to pathophysiology of diabetes. Invited Speaker. Leaders in Science Seminars. Garvan Institute of Medical Research. Sydney,

Australia (Host: J Gunton MD PhD) 2014 Growth factor regulation of mitochondrial function in pancreatic beta cells. Invited Speaker.

Mitochondria and Disease Symposium, Cambridge, MA (international attendees) 2014 Significance of regeneration of beta cells in type 1 diabetes. Invited Speaker. Seminar at the

Banting Best Diabetes Center (BBDC). Toronto, Canada. (Host: G Lewis MD). 2014 Transgenic and translational approaches to investigate the pathophysiology of diabetes.

Oxford Center for Diabetes Endocrinology and Metabolism (OCDEM) Seminar, Oxford, England (Host: P Rorsman PhD).

2014 Significance of insulin and IGF-1 receptors in pancreatic islet biology. Invited Speaker.

Rachmiel Levine Symposium. City of Hope, Duarte, CA (Hosts: D. Harlan MD; A. Stewart MD) (international attendees)

2014 Using iPS cells to interrogate diabetes complications. Invited Speaker. Keystone Symposium

on Diabetes Complications. Vancouver, Canada (Hosts: M, Brownlee MD, M Breyer MD, S Quaggin MD).

2014 Circulating factors regulating beta-cell growth. Merck Scientific Advisory Board Meeting,

Berlin, Germany (Host: Steven Kahn MD) 2014 Novel concepts in growth factor signaling in pancreatic islets. Invited Speaker. Islet Keystone

Symposium (D3). Keystone, CO (Hosts: Rohit Kulkarni MD PhD; Raghu Mirmira MD PhD, Eckhard Lammert PhD)

2014 Liver-derived beta-cell growth factors. Invited speaker. Symposium: Circulating factors

affecting beta cell function and mass. 74th Annual Meeting of the American Diabetes Association, San Francisco, CA. (international attendees).

31

2014 Growth factor and GLP-1 signaling pathways in the regulation of the endocrine pancreas. Nutrients, the digestive tract and diabetes. Invited speaker. 1st Banting and Best Diabetes Center-Joslin Diabetes Center Conference, MaRS Center, Toronto, Canada (Hosts: Gary Lewis MD; George King MD)

2015 Liver-derived beta cell regenerative factors. Invited speaker. Rachmiel Levine Diabetes and

Obesity Symposium on Novel molecules that induce human beta cell replication. San Diego, CA (Hosts: D. Harlan, MD; AF Stewart MD). (international attendees)

2015 Linking liver and pancreas action in metabolism. Invited speaker. 97th Endocrine Society

Annual Meeting. San Diego, CA (international attendees). 2015 Significance of beta cell regeneration in type 1 diabetes. Invited speaker. Experimental

Biology Meeting 2015. Symposium on Protecting and restoring functional beta cell ams in tye 1 diabetes: Research from bench to bedside. Boston, MA (Hosts: C Evans-Molina MD; P. Fueger MD). (international attendees).

2015 Keynote Speaker. Symposium on Type 2 Diabetes Research.1 Rina and Avner Schneur

Center of Type 2 Diabetes Research. Technion Israel Institute of Technology, Haifa, Israel. (Host: S. Levenberg MD; E. Karnieli MD)

2015 Growth factor signaling and beta cell mass. Invited speaker. Joint Meeting of the Islet Study

Group and Beta Cell Workshop, Menachem Begin Center, Jerusalem, Israel. (Hosts: Y. Dor PhD; B. Glaser, MD)

2015 Using indiced pluripotent stem cells to interrogate the pathophysiology of diabetes. Invited

speaker. European Asssociation for the Study of Diabetes (EASD) Study Group on Genetics of Diabetes. Symposium: Animals models and cell research. 5th Meeting, Krakow, Poland. (Host: M. Malecki MD PhD)

2015 Growth factor signaling in islets in diabetes models. Invited speaker. Symposium

“Contributions of pancreatic hormones to regulation/dysregulation of glucose metabolism – revisiting islet endocrine function and dysfunction”. 58th Annual Meeting of the Japan Diabetes Society. Shimonoseki, Japan. (Host: Y. Tanizawa MD).

2015 Invited speaker. Endocrine Seminar at University of Kumamoto Medical School. Kumamoto,

Japan. (Host: E Arakai MD) 2015 Approaches to enhance functional beta cell mass. Invited Speaker. Symposium on Adaptation

of beta cells to hypoglycemia. Frontiers in Pancreatic Research. Gordon Research Conference, Mount Holyoke College, South Haldey, MA (internataionl attendees). (Host: M. Solimena MD; D. Simeone PhD)

2015 Invited speaker. 2nd Banting and Best Diabetes Center-Joslin-University of Copenhagen

Conference. Islet cell plasticity in diabetes therapy. Carlsberg Museum, Copenhagen, Denmark (Hosts: G. King MD; J. Nielsen PhD)

2015 Invited speaker. American Diabetes Association-Primer Symposium, Bangalore, India.

(Hosts: A. Sosale MD; S. Dagogo-Jack MD)

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2015 “Regeneration of beta cells: a therapeutic option to restore beta-cell health”. Invited speaker. Symposium on “Dedifferentiation, redifferentiation and transdifferentiation mechanisms regulating beta-cell mass”. International Diabetes Federation, Word Diabetes Congress, Vancouver, Canada (Host: S. Kahn MD)

2015 Using stem cell science and systems biology to tackle diabetes in the 21st century. Nominated for

the Prof. M.S.S. Ahuja ORATION – 43rd Annual Meeting of the Research Society for the Study of Diabetes in India (RSSDI), Lucknow, India. (Host: Prof. S. Bajaj MD)

2015 The β-cell - a central player in glucose homeostasis. Invited Speaker. Symposium on “Whole-

body glucose homeostasis”. World Congress on insulin resistance, diabetes and cardiovascular disease (WCIRDC), Los Angeles, (Hosts: Y. Handelsman MD: R. DeFronzo MD). (international attendees)

2016 Identifying SerpinB1 as a beta cell growth factor: implications for treatment of type 2 diabetes.

Invited Plenary Speaker. DEBATE. Bengaluru (Hosts: KM Prasanna Kumar MD; Aravind SR MD; K. Seshadri MD).

2016 Novel concepts in regeneration of beta cells. Invited Speaker. Symposium 15: Current topics of

islet biology. 59th Annual Meeting of Japan Diabetes Society. Kyoto, Japan. (Host: N. Inagaki MD).

2016 Update on insulin signalling in beta cells. Bunkyo Diabetes Seminar Tokyo, Japan. (Host: K.

Ueki MD PhD). 2016 Modeling type 1 diabetes using induced pluripotent stem cells. Invited Speaker. 76th Annual

Meeting of the ADA. “Modeling human disease variants” New Orleans, LA. (international attendees)

2016 Growth factor regulation of β-cell cycle progression. Islet Study Group 2016, Garmisch-

Partenkirchen, Germany. (Host: H. Lickert PhD). 2016 Novel factors promoting human β-cell proliferation. 4th Annual Helmholtz - Nature Medicine

Diabetes Conference, Munich (Hosts: M. Tschop PhD, H. Lickert PhD, R. Levinson PhD). 2016 Using iPS cells to interrogate diabetes complications. 3rd Heidelberg International Symposium on

Diabetic Complications. Heidelberg, Germany. (Host: P. Nawroth MD; S. Herzig PhD). 2016 Novel proteins and pathways that regulate human β-cell proliferation. “β-cell: From Bench to

Bedside”. First EuroDia Meeting. Centre Europeen d’Etude du Diabete, Strasbourg Medical School, Strasbourg, France. (Host: K. Bouzakiri PhD).

2017 A role for microRNAs in diabetes and its complications. Keystone Meeting. Keystone, Colorado

(Organizer of Diabetes J3; Co-organizers: J Lin PhD; C. Semenkovich MD) 2017 Growth Factor signaling in islet cells. 17th International Symposium on Insulin Receptor and

Insulin Action. Nice, France (Hosts: M. VanObbergen MD PhD; H. Haring MD).

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2017 Genome Editing and Diabetes. American Diabetes Association- Primer Academy of Medical Sciences Clinical Update in Diabetes, Bangalore, (Hosts: Aravind SR MD, K.M.P. Kumar MD, K Seshadri MD)

2017 GLP-1 and beta cells. American Diabetes Association- Primer Academy of Medical Sciences

Clinical Update in Diabetes, Bangalore, (Hosts: A. Sosale MD, K.M.P. Kumar MD, K Seshadri MD)

2017 The many faces of type 2 diabetes. American Diabetes Association- Primer Academy of Medical

Sciences Clinical Update in Diabetes, Bangalore, (Hosts: A. Sosale MD, K.M.P. Kumar MD, K Seshadri MD)

2017 The new biology of diabetes: From Charaka-Sushruta to CRISPR. Dr. H.J. Mehta Memorial

Oration. St. John’s Medical College Alumni Association Bangalore, India (Hosts: P. Pais MD; M Vaz MD).

2017 Growth Factor Signaling Regulation of Islet Cell Regeneration. University of California, San

Francisco. San Francisco, California (Host: Julie B. Sneddon, PhD). 2017 Role of GLP-1 activation in improving beta cell function in diabetes. XXVI IMSS National

Health Research Forum. San Luis Potosi, Mexico (Host: Marcelino Hernandez-Valencia MD). 2017 Experimental studies for the prevention and delay in progression of Diabetes. XXVI IMSS

National Health Research Forum. San Luis Potosi, Mexico (Host: Marcelino Hernandez-Valencia MD).

2017 Growth Factor Regulation of Islet Biology. Heidelberg International Symposium. Heidelberg,

Germany (Host: P. Nawroth MD; S. Herzig PhD). 2017 Growth factor regulation of islet biology. Invited Speaker, IRCM Montreal. Montreal, Canada

(Host: Mathieu Ferron, PhD). 2018 β-cell proliferation in type 1 diabetes. Invited Speaker. Keystone Symposium. Frontiers in Islet

Biology and Diabetes. Keystone, Colorado 2018 Role of growth factor regulation of cell cycle in adaptive β-cell proliferation. Invited Speaker.

Symposium on “Roads to β-cell failure in type2 diabetes”. 100th Annual Meeting of the Endocrine Society, Chicago

2018 Growth factor signaling in the regulation of islet cell biology. Invited speaker. Institute for

Molecular and Cell Biology, Proteos. Singapore (Host: AKK Teo PhD) 2018 Using iPS cells to interrogate the regulation of tissue-specific complications in diabetes. Invited

speaker. The 12th Diabetes leading edge conference. Chiba, Japan (Host: Inagaki MD PhD). 2018 ADA-PAMS, Bengaluru (Hosts: Aravind Sosale MD; KM Prasanna Kumar MD; K Sheshadri

MD) 2018 Using stem cells to interrogate diabetes complications. Invited speaker. Adelaide, Australia

(Host: J. Gunton)

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2018 Adelaide, Australia 2018 ESA/ADS, Plenary Lecture. Endocrine Society of Australia, Adelaide, Australia (Host: W. Inder

MD). 2018 Epitranscripotmics: a new layer of regulation in islet biology and metabolism. Albert Renold

Islet Prize Lecture. European Association for the Study of Diabetes, Berlin. 2018 Beta cell protection and recovery. Invited speaker. University of Copenhagen. Joint Meeting

with Joslin Diabetes Center and Banting and Best Diabetes Center, Toronto. Copenhagen, Denmark

2018 Is Diabetes Heritable? A role for Epigenetics and Epitranscriptomics. Invited speaker. ADA-

PAMS Clinical Update in Diabetes. Bengaluru, India. (Hosts: Aravind Sosale MD; KM Prasanna Kumar MD; K Sheshadri MD).

2019 Can we prevent/reverse type 1 diabetes by enhancing beta cell numbers? Seminars in Diabetes

and Metabolism. Rome, Italy (Host: V. Trischitta MD). 2019 An unexpected role for SerpinB1 in regulating glucose homeostasis. Invited Speaker. The

Serpins 2019 Conference. Sevilla, Spain. (Host: J Huntingotn PhD). 2019 Can we prevent/reverse type 1 diabetes by enhancing beta cell mass? Seminar. Klinik fur

Diabetologie und Endokrinologie, UniverstatsSpital, Zurich (Host: J. Krutzfeldt MD) 2019 m6A mRNA methylation - an emerging layer of regulation in islet biology and metabolism.

Seminar. Institute of Molecular Health Sciences, ETH Honggerberg, Zurich. (Host: M. Stoffel MD PhD).

2019 m6A mRNA methylation in islets and metabolic tissues. Invited Speaker. Bioenergetics and its

dysregulation in diabetes. Joslin International Symposium. Joint with Banting and Best Diabetes Center, Toronto and University of Copenhagen. Boston (Hosts: TK Blackwell MD PhD: RN Kulkarni MD PhD).

2019 Modeling diabetic associated kidney complications using human induced pluripotent stem

cells. Invited speaker. 5th Heidelberg International Symposium on Diabetic Complications. Heidelberg, Germany (Host: P. Nawroth MD; S. Herzig PhD)

Report of Technological and Other Scientific Innovations 1. Inventors: Maratos-Flier, E (Newton, MA); Kulkarni; Rohit N. (Brookline, MA), Pissios, Pavlos (Boston, MA); Assignee (Joslin Diabetes Center, Boston, MA; Appl. No. 10/355,645. Filed 01/31/03, Issued 9/5/06, U.S. Patent No. 7,101,845 This report would be useful to understand the potential mechanism(s) that underlie the pathways that mediate the regeneration of pancreatic beta cells, a major area of study in both type 1 and type 2 diabetes. 2. Inventors: Maratos-Flier, E (Newton, MA); Kulkarni; Rohit N. (Brookline, MA), Pissios, Pavlos (Boston, MA); Assignee (Joslin Diabetes Center, Boston, MA; Appl. No. 11/509,963. filed 08/24/06, Issued 08/14/07, U.S. Patent No. 7,256,176 B2

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This modification of the previous report would be useful to understand the potential mechanism(s) that underlie the pathways that mediate the proliferation of pancreatic beta cells. 3. Inventors: Rohit N. Kulkarni (Chestnut Hill, MA), Chong Wee Liew (Brookline, MA); Assignee (Joslin Diabetes Center, Boston, MA); U.S. Provisional Application No. 61/537,234; Pierce Atwood Docket No. JDP-154PR01 (29060-3125). Methods for treating obesity and insulin resistance with TRIP-Br2 inhibitors. 4. Inventors: Rohit N. Kulkarni (Chestnut Hill, MA): Abdel El Ouamaari (Brookline, MA); Assignee Joslin Diabetes Center, Boston, MA): International Application No.: PCT/EP2014/053419; U.S. Provisional Application No. 61/767,948; Pierce Atwood Docket No. JDP-162US01 and US02: Methods of therapeutic beta-cell regeneration and function. European Patent Application: Serpins: methods of therapeutic beta cell regeneration and function. # 13306284.4-1456/2851086 Report of Education of Patients and Service to the Community No presentations below were sponsored by outside entities. Activities 2006- talks to the lay community in educational outreach events focused on diabetes, talks to trainees related to career advice (organized by the local ADA) and on stem cell research (organized by HSCI), in Boston and other states in the US

Report of Scholarship Publications: Complete List of Published Work in MyBibliography (219):

http://www.ncbi.nlm.nih.gov/sites/myncbi/16A5Qwqeri45n/bibliography/47205880/public/?sort=date&direction=ascending. h-index: 65 (Google Scholar) Peer Reviewed Publications in print or other media (*, corresponding) Research Investigations: 1. Sheela ML, Kurpad AV, Kulkarni RN, Shetty PS. Prediction of steady state oxygen consumption during

norepinephrine infusion in man. Metabolism 10:907-909, 1988. 2. Kurpad AV, Kulkarni RN, Shetty PS. Potentiation of thermogenic responses during norepinephrine

infusions in human subjects. Med Sci Res 16:997-998 1988. 3. Kulkarni RN, Kurpad AV, Shetty PS. Vascular adrenoceptor sensitivity to graded doses of norepinephrine

infusions in undernourished subjects. Ind J Med Res 88:427-433, 1988. 4. Soares MJ, Sheela ML, Kurpad AV, Kulkarni RN, Shetty PS. The influence of different methods on basal

metabolic rate measurements in human subjects. Am J Clin Nutr 50:731-736, 1989. 5. Kurpad AV, Kulkarni RN, Vaz M, Shetty PS. Repeated infusions of identical doses of norepinephrine

show potentiation of metabolic responses in human subjects. Metabolism 38:979-982, 1989. 6. Kurpad AV, Kulkarni RN, Sheela ML, Shetty PS. Thermogenic responses to graded doses of

noradrenaline in undernourished subjects. Br J Nutr 61:201-208, 1989. 7. Kurpad AV, Kulkarni RN, Shetty, PS. Reduced thermoregulatory thermogenesis in undernutrition. Eur J

Clin Nutr 43:27-33, 1989. 8. Vaz M, Kumar MVS, Rodrigues D, Kulkarni RN, Shetty PS. Variability in cardiovascular and plasma

norepinephrine responses to head-up-tilt in healthy human subjects. J Auton Ner Sys 36:201-208, 1991.

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9. Vaz M, Kulkarni RN, Soares MJ, Kurpad AV, Shetty PS. Thermogenic responses to norepinephrine are unaltered following energy supplementation in chronically energy deficient human subjects. Eur J Clin Inv 21:27-32, 1991.

10. Kulkarni RN, Vaz M, Shetty PS. Absence of enhanced post-exercise metabolic rate in chronically undernourished human subjects. Med Sci Res 19:601-602, 1991.

11. Vaz M, Jayarajan MP, Kulkarni RN, Balasubramanyam A, Shetty PS. Parasympathetic tone in chronic energy deficient human subjects. Nutr Res 12 (4-5):613-620, 1992.

12. Piers LS, Soares MJ, Kulkarni RN, Shetty PS. Thermic effect of a meal. 3. Effect of dietary supplementation in chronically undernourished subjects. Br J Nutr 67:187-194,1992.

13. Kurpad AV, Kulkarni RN, Rodriguez GD, Shetty PS. Characteristics of norepinephrine stimulated thermogenesis in undernourished subjects. J Biosciences 17:293-303, 1992.

14. Soares MJ, Kulkarni RN, Piers LS, Vaz M, Shetty PS. Energy supplementation reverses changes in basal metabolic rates in chronically undernourished human subjects. Br J Nutr 68:593-602, 1992.

15. Kulkarni RN, Shetty PS. Net mechanical efficiency during stepping in chronically energy-deficient human subjects. Ann Hum Biol 19:421-425, 1992.

16. Vaz M, Kulkarni RN, Rodriguez D, Shetty PS. Immediate heart rate responses to head-up tilt in healthy human subjects: response characteristics and variability. Ind J Physiol Pharmacol 37:323-327, 1993.

17. Vaz M, Kumar MVS, Kulkarni RN, Rodriguez D, Shetty PS. Variability of cardiovascular and plasma noradrenaline responses to sustained isometric contraction in normal human subjects. Clin Sci 85:45-49, 1993.

18. Kulkarni RN, Kurpad AV, Shetty PS. Reduced post-exercise recovery O2 consumptions: an adaptive response in chronic energy deficiency? Metabolism 42:544-547, 1993.

19. Vaz M, Kulkarni RN, Leo L, Shetty PS. Plasma norepinephrine kinetics are unaltered in chronically undernourished adult subjects. Eur J Clin Nutr 48:30-37, 1994.

20. Olmos G, Kulkarni RN, Haque M, MacDermot J. Imidazolines stimulate release of insulin from RIN 5AH cells independently from I1 and I2 imidazoline receptors. Eur J Pharmacol 262:41-48, 1994.

21. Kulkarni RN, Smith DM, Ghatei MA, Bloom SR. A 67 kDa protein mediates pituitary adenylate cyclase activating polypeptide and vasoactive intestinal peptide stimulated secretion of insulin in a hamster clonal beta-cell line. J Endocrinol 147:121-130, 1995.

22. Kulkarni RN, Wang Z, Akinsanya KO, Bennet WM, Wang R, Smith DM, Ghatei MA, Byfield PGH, Bloom SR. Pyroglutamyl-phenylalanyl-proline amide attenuates thyrotropin-releasing hormone-stimulated insulin secretion in perifused rat islets and insulin secreting clonal beta-cell lines. Endocrinology 136:5155-5164, 1995.

23. Kulkarni RN, Smith DM, Ghatei MA, Jones PM, Bloom SR. Investigation of the effects of antisense oligodeoxynucleotides to islet amyloid polypeptide mRNA on insulin release, content and expression. J Endocrinol 151:341-348, 1996.

24. Wang ZL *, Kulkarni RN *, Wang RM, Smith DM, Ghatei MA, Byfield PGH, Bennet WM & Bloom SR. Possible evidence for endogenous production of a novel galanin-like peptide. J Clin Invest 100: 189-196, 1997. ( *first authors)1 PMCID: PMC508179

25. Kulkarni RN, Wang ZL, Wang RM, Hurley JD, Smith DM, Ghatei MA, Withers DJ, Gardiner JG, Bailey CJ, Bloom SR. Leptin rapidly suppresses insulin secretion from insulinoma cells, rat and human islets and, in vivo, in mice. J Clin Invest 100:2729-2736, 1997. PMCID: PMC508476

26. Morgan DG, Kulkarni RN, Hurley JD, Wang ZL, Wang RM, Karlsen AE, Bloom SR & Smith DM. Inhibition of glucose stimulated insulin secretion by neuropeptide Y is mediated via the Y1 receptor and inhibition of adenylyl cyclase in RIN 5AH rat insulinoma cells. Diabetologia 41:1482-1491, 1998. PMID:9867216

27. Vaz M, Kulkarni RN, Shetty PS. Metabolic responses to repeated infusions of norepinephrine in chronically energy deficient human subjects. Indian J Med Res 107:1030108, 1998. PMID:9540286

1 Co-first authorship

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28. Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR. Tissue-specific knockout of the insulin receptor in the pancreatic beta-cell creates an insulin secretory defect similar to that in type-2 diabetes. Cell 96:329-339, 1999.

29. Kulkarni RN, Winnay JN, Daniels M, Bruning JC, Flier SN, Hanahan D, Kahn CR. Altered function of IRS-1 deficient mouse islets and cultured beta-cell lines. J Clin Invest 104:R69-R75, 1999. PMCID: PMC409887

30. Kulkarni RN, Wang Z-L, Wang R-L, Smith DM, Ghatei MA, Bloom SR. Glibenclamide but not other sulphonylureas stimulates release of neuropeptide Y from perifused rat islets and hamster insulinoma cells. J Endocrinol 165(2):509-518, 2000

31. Aspinwall CA, Qian W-J, Roper MG, Kulkarni RN, Kahn CR, Kennedy RT. Roles of insulin receptor substrate-1, phosphatidylinositol 3-kinase and release of intracellular Ca2+ stores in insulin-stimulated insulin secretion in beta-cells. J Biol Chem 275(29):22331-22338, 2000

32. Michael MD, Kulkarni RN, Postic C, Previs S, Shulman GI, Magnuson MA, Kahn CR. Loss of insulin signaling in the hepatocyte leads to severe primary insulin resistance and progressive hepatic dysfunction. Mol Cell 6:87-97, 2000.

33. Mauvais-Jarvis F, Virkamakii A, Michael MD, Winnay JN, Zisman A, Kulkarni RN, Kahn CR. A model to explore the interaction between muscle insulin resistance and beta-cell dysfunction in the development of type 2 diabetes. Diabetes 49(12): 2126-2134, 2000.

34. Ludwig DS, Tritos NA, Mastaitis JW, Kulkarni RN, Kokkotou E, Elmquist J, Lowell B, Flier JS, Maratos-Flier E. Melanin concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest 107:379-386, 2001. PMCID: PMC199192

35. Leibiger B, Leibiger IB, Moede T, Kemper S, Kulkarni RN, Kahn CR, Berggren P-O. Insulin signaling through A and B type insulin receptors selectively up-regulates transcription of the insulin- and glucokinase-genes in pancreatic beta cells. Mol Cell 7: 559-570, 2001.

36. Flier SN*, Kulkarni RN*, Kahn CR. Evidence for a circulating islet cell growth factor in insulin resistance states. (*first authors)1. Proc Natl Acad Sci 98:7475-7480, 2001. PMCID: PMC34693

37. Roper MG, Qian W-J, Zhang B, Kulkarni RN, Kahn CR, Kennedy RT. Effect of the insulin mimetic L-783,281 on intracellular [Ca2+] and insulin secretion from pancreatic beta-cells. Diabetes 51 Suppl 1:S43-S49, 2002.

38. Kulkarni RN*, Holzenberger M, Shih D, Ozcan U, Stoffel M, Magnuson MA, Kahn CR. β-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass. Nat Genet 31(1):111-115, 2002

39. Laustsen PG, Michael MD, Crute BE, Cohen SE, Ueki K, Kulkarni RN, Keller SR, Lienhard GE, Kahn CR. Lipoatrophic diabetes in IRS1-/-/IRS3-/- double knockout mice. Genes & Dev 16(24), 3213-3221, 2002

40. Kulkarni RN, Almind K, Winnay JN, Goren HJ, Ueki K, Okada T, Kahn CR. Impact of genetic background on the development of hyperinsulinemia and diabetes in IR/IRS-1 double heterozygous mice. Diabetes 52:1528-1534, 2003

41. Almind K, Kulkarni RN, Lannon S, Kahn CR. Identification of interactive loci with linkage to insulin and leptin in mice with genetic insulin resistance. Diabetes 52:1535-1543, 2003

42. Du K, Herzig S, Kulkarni RN, Montminy M. TRB-3: A tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science 300:1574-1577, 2003

43. Jhala US, Canettieri G, Screaton R, Kulkarni RN, Krajewski S, Reed J, Walker J, Lin X, White M, Montminy M. cAMP promotes pancreatic beta cell survival via CREB mediated induction of IRS-2. Genes & Dev 17:1575-1580, 2003 PMCID: PMC196130

44. Jiang ZY, He Z, King BL, Kuroki T, Opland DM, Suzuma K, Suzuma I, Ueki K, Kulkarni RN, Kahn CR, King GL. Characterization of multiple signaling pathways of insulin in the regulation of vascular endothelial growth factor expression in vascular cells and angiogenesis. J Biol Chem 278:31964-31971, 2003

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45. Rosen ED, Kulkarni RN, Costa J, Sarraf P, Ozcan U, Okata T, Hsu C-H, Eisenman D, Magnuson MA, Gonzalez FJ, Kahn CR, Spiegelman BM. Targeted elimination of peroxisome proliferator-activated receptor gamma in beta cells leads to abnormalities in islet mass without compromising glucose homeostasis Mol Cell Biol 20:7222-7229, 2003 PMCID: PMC230305

46. Hennige AM, Burks DJ, Ozcan U, Kulkarni RN, Ye J, Park S, Schubert M, Fisher TL, Dow MA, Leshan R, Zakaria M, Mossa-Basha M, White MF. Up-regulation of insulin receptor substrate-2 in pancreatic beta-cells prevents diabetes. J Clin Invest 112:1521-1532, 2003 PMCID: PMC259126

47. Otani K*, Kulkarni RN*, Baldwin AC, Kruetzfeldt J, Ueki K, Stoffel M, Kahn CR, Polonsky KS. Reduced beta-cell mass and altered glucose sensing impair insulin secretory function in mice with pancreatic beta-cell knockout of the insulin receptor. (* first authors)1 Am J Physiol Endocrinol Metab 286:E41-E49, 2004

48. Goren HJ, Kulkarni RN, Kahn CR. Glucose homeostasis and tissue transcript content of insulin signaling intermediates in four inbred strains of mice: C57Bl/6, C57BLKS/6, DBA/2, and 129X1. Endocrinology, 145:3307-3323, 2004

49. Kulkarni RN*, Roper MG, Dahlgren G, Shih DQ, Kauri LM, Peters JL, Stoffel M, Kennedy RT. Insulin secretory defect in insulin receptor substrate 1 null mice is linked with reduced calcium signaling and expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)-2b and -3. Diabetes 53:1517-1525, 2004.

50. Koo S-H, Herzig S, Lee C-H, Hedrick S, Kulkarni RN, Evans R, Olefsky J, Montminy M. PGC-1 promotes insulin resistance in liver via PPAR-alpha dependent induction of TRB3. Nat Med 10:530-534, 2004

51. Kulkarni RN*, Jhala US, Winnay JN, Krajewski S, Montminy M, Kahn CR. PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance. J Clin Invest 114(6):828-836, 2004 PMCID: PMC516256

52. Bates SH, Kulkarni RN, Seifert M, Myers MG Jr. Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis. Cell Metabolism 1(3):169-178, 2005

53. Hennige AM, Ozcan U, Okada T, Jhala U, Schubert M, White MF, Kulkarni RN*. Alterations in growth and apoptosis of insulin receptor substrate-1 deficient beta cells. Am J Physiol Endocrinol Metab, 289:E337-E346, 2005

54. Gunton JE, Kulkarni RN, Yim SH, Okada T, Hawthorne WJ, Tseng YH, Roberson RS, Ricordi C, O’Connell PJ, Gonzalez FJ, Kahn CR. Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. Cell 122:337-349, 2005 PMID: 16096055

55. He Z, Opland DM, Way KJ, Ueki K, Bodyak N, Kang PM, Izumo S, Kulkarni RN, Wang B, Liao R, Kahn CR, King GL. Regulation of Vascular Endothelial Growth Factor Expression and Vascularization in the Myocardium by Insulin Receptor and PI3K/Akt Pathways in Insulin Resistance and Ischemia. Arterioscler Thromb Vasc Biol. 26(4):787-93. 2006

56. Ueki K, Okada T, Hu J, Liew CW, Assmann A, Dahlgren GM, Peters JL, Shackman JG, Zhang M, Artner I, Satin LS, Stein R, Holzenberger M, Kennedy RT, Kahn CR, Kulkarni RN*. Total insulin/IGF-1 resistance in pancreatic beta-cells causes overt diabetes. Nat Genetics 38(5):583-588, 2006

57. Qi L, Heredia J, Altarejos JY, Screaton R, Goebel N, Niessen S, MacLeod IX, Liew CW, Kulkarni RN, Bain J, Newgard C, Nelson M, Evans RM, Yates J Montminy M. TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism. Science 312(5781):1763-6, 2006.

58. Koh H-J, Arnolds DE, Fujii N, Tran TT, Rogers MJ, Jessen N, Li Y, Liew CW, Ho RC, Hirshman MF, Kulkarni RN, Kahn CR, Goodyear LJ. Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis and decreases TRB3. Mol Cell Biol 26(22):8217-27, 2006, doi:101128/MCB.00979-06 PMCID: PMC1636784

59. Pissios P, Ozcan U, Kokkotou E, Okada T, Liew CW, Liu S, Peters JN, Dahlgren G, Karamchandani J, Kudva YC, Kurpad AJ, Kennedy RT, Maratos-Flier E & Kulkarni RN*. Melanin-Concentrating Hormone is a Novel Regulator of Islet Growth and Function. Diabetes 56:311-319, 2007

1 Co-first authorship

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60. Okada T, Liew CW, Hu J, Hinault C, Michael MD, Krutzfeldt J, Yin C, Holzenberger M, Stoffel M, Kulkarni RN*. Insulin receptors are critical for islet compensatory growth response to insulin resistance. Proc Natl Aca Sci USA 104:8977-8982, 2007. PMCID: PMC1885613

61. Matsumara K, Chang BH-J, Fujiyama M, Chen W, Kulkarni RN, Eguchi Y, Kimura H, Kojima H, Chan L. Aquaporin is a beta-cell protein and regulator of intra-islet glycerol content and glycerol kinase activity, beta-cell mass, and insulin production and secretion. Mol Cell Biol 27(17):6026-37, 2007 PMCID: PMC1952143

62. Morioka T, Asilmaz E, Hu J, Dishinger JD, Kurpad AJ, Elias CF, Li H, Elmquist JK, Kennedy T, Kulkarni RN*. Disruption of leptin receptor expression in pancreas directly impacts beta-cell islet growth and function. J Clin Invest 117(10):2860-2868, 2007 PMCID: PMC1994606

63. Handschin C, Choi CS, Chin S, Kim S, Kawamori D, Kurpad AJ, Neubauer N, Hu J, Liu F, Maratis-Flier E, Mootha VK, Kim Y-B, Kulkarni RN, Shulman GI, Spiegelman BC. Abnormal glucose homeostasis in skeletal muscle-specific PGC-1a knockout mice through skeletal muscle-pancreatic beta-cell crosstalk. J Clin Invest 117(11):3463-3474, 2007 PMCID: PMC2000810

64. Page KA, Dejardin S, Kahn CR, Kulkarni RN, Herold K, Inzucchi S. Type B insulin resistance syndrome in a hospitalized patient with diabetes mellitus, responsive to immunotherapy. Nat Clin Pract Endocrinol Med 3(12):835-40, 2007

65. Petyuk V, Qian W-J, Hinault C, Gritsenko M, Singhal M, Monroe M, Camp D, Kulkarni RN *, Smith RD. Characterization of the mouse pancreatic islet proteome and comparative analysis with other mouse tissues. J Proteome Res 7(8):3114-26, 2008 (corresponding)2 PMCID: PMC2749725

66. Deangelis AM, Heinrich G, Bowman TA, Patel PR, Dai T, Lee SJ, Hong E-G, Jung DY, Assmann A, Kulkarni RN, Kim JK, Najjar SM. CEACAM1: A Link Between Insulin and Lipid Metabolism. Diabetes 57(9):2296-303, 2008. PMCID: PMC2518480

67. Tseng Y-H, Kokkotou E, Huang TL, Taniguchi CM, Tran TT, Suzuki S, Schulz TJ, Espinoza DO, Winnay JN, Yamomoto Y, Ahrens MJ, Dudley AT, Norris AW, Kulkarni RN, Kahn CR. Novel role of bone morphogenetic protein-7 in brown adipogenesis and energy expenditure. Nature 454:1000-4, 2008. PMCID: PMC2745972

68. Hisanaga E, Nagasawa M, Ueki K, Kulkarni R.N, Mori M. M, Kojima I. Regulation of calcium-permeable TRPV2 channel by insulin in pancreatic beta cells. Diabetes 58(1):174-84, 2009. PMCID: PMC260668

69. Torii S, Saito N, Kawano A, Hou N, Ueki K, Kulkarni RN, Takeuchi T. Gene silencing of phogrin unveils its essential role in glucose-responsive pancreatic beta cell growth. Diabetes 58(3):682-92, 2009. PMCID: PMC2646067

70. Assmann A, Ueki K, Winnay J, Kadowaki T, Kulkarni RN*. Glucose effects on growth and survival of beta cells requires the activation of proteins in the insulin signaling pathway. Mol Cell Biol 29(11):3219-28, 2009. PMCID: PMC2682019

71. Kawamori D, Kurpad AJ, Hu J, Liew CW, Shih JL, Ford EL, Herrera PL, Polonsky KS, McGuiness OP, Kulkarni RN*. Insulin signaling in alpha-cells modulates glucagon secretion in vivo. Cell Metabolism 9:350-361, 2009. PMCID: PMC2694613

72. Borowiec M, Liew CW, Thompson R, Boonyasrisawat W, Hu J, Mlynarski WM, El Khattabi I, Kim SH, Marselli L, Rich SS, Krolewski AS, Bonner-Weir S, Sharma A, Sale M. Mychaleckyj JC, Kulkarni RN, Doria A. Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc Natl Acad Sci USA 106(34):14460-14465, 2009. PMCID: PMC2732833

73. Zhou J-Y, Petritis BO, Petritis K, Norbeck AD, Weitz K, Moore, RJ, Camp DG, Kulkarni RN, Smith RD, Qian W-J. Mouse-specific tandem IgY7-superix immunoaffinity separations for improved LC-MS/MS coverage of the plasma proteome. J Proteome Res 8(11):5387-5395, 2009. PMCID: PMC2783519

74. Kawamori D, Kulkarni RN*. Insulin modulation of glucagon secretion: the role of insulin and other

2 Co-corresponding author

40

factors in the regulation of glucagon secretion. Islets 1(3):276-279, 2009 75. Liu S, Okada T, Assmann A, Soto J, Liew CW, Bugger H, Shirihai O, Abel ED, Kulkarni RN*. Insulin

signaling regulates mitochondrial function in pancreatic beta-cells.PLoS One 4(11): e7983, 2009. PMCID: PMC2776992

76. Zhang Z, Liew CW, Handy DE, Zhang Y, Leoold JA, Hu J, Guo L, Loscalzo J, Kulkarni RN, Stanton RC. High glucose inhibits glucose-6-phosphate dehydrogenase leading to increased oxidative stress and beta cell apoptosis. FASEB J, 24(5):1497-1505, 2010. PMCID: PMC2879949

77. Robertson S, Ishida-Takahashi R, Tawara I, Hu J, Jones JC, Kulkarni RN, Myers MG Jr. Insufficiency of Jak2-autonomous leptin receptor signals for most physiologic leptin action. Diabetes 59(4):782-790, 2010. PMCID: PMC2844825

78. Georgia S, Hinault C, Kawamori D, Hu J, Meyer J, Kanji M, Bhushan A, Kulkarni RN*. Cyclin D2 is essential for the compensatory hyperplastic response to insulin resistance in rodents. Diabetes 59(4):987-996, 2010. PMCID: PMC2844846

79. Bouche C, Lopez X, Fleischmann A, Cypess AM, O’Shea S, Stefanovski D, Bergman RN, Rogatsky E, Stein DT, Kahn CR, Kulkarni RN, Goldfine AB. Insulin enhances glucose-stimulated insulin secretion in healthy humans. Proc Natl Acad Sci USA, 107(10):4770-4775, 2010. PMCID: PMC2842068

80. Cornu M, Modi H, Kawamori D, Kulkarni RN, Joffraud M, Thorens B. Glucagon-like-peptide-1 (GLP-1) increases beta cell glucose competence and proliferation by translational induction of insulin-like growth factor-1 receptor (IGF-1R) expression. J Biol Chem 285(14):10538-45, 2010. PMCID: PMC2856261

81. Cheng K, Ho K, Stokes R, Scott C, Mei Lau S, Hawthorne WJ, O’Connell PJ, Loudovaris T, Kay TW, Kulkarni RN, Okada T, Wang X, Yim S, Shah Y, Grey ST, Biankin AV, Kench JG, Laybutt DR, Gonzalez FJ, Kahn CR, Gunton JE. Hypoxia-inducible factor-1α regulates beta-cell function in mice and in human islets. J Clin Invest 120(6):2171-83, 2010. PMCID: PMC2877560

82. Liew CW, Bochenski J, Kawamori D, Hu J, Leech C, Krzysztof W, Malecki M, Warram J, Qi L, Krolewski A, Kulkarni RN*. The pseudokinase tribbles homolog 3 interacts with ATF4 to negatively regulate insulin exocytosis in human and mouse beta-cells. J Clin Invest 120(8):2876-2888, 2010. PMCID: PMC2912176

83. Reiner T, Kohler R, Liew CW, Hill JA, Gaglia J, Kulkarni RN, Weissleder R. Near infrared fluorescent probe for in vivo imaging of pancreatic beta cells. Bioconjug Chem 21(7):1362-1368, 2010. PMCID: PMC2912453

84. Vesterhus M, Ræder H, Kurpad AJ, Kawamori D, Molven A, Kulkarni RN, Kahn CR, Njølstad PR. Pancreatic function in Carboxyl-Ester Lipase knockout mice. Pancreatology 10(4):467-476, 2010. PMCID: PMC2968766

85. Kaneko K, Ueki K, Takahashi N, Hashimoto S, Okamoto M, Awazawa M, Okazaki Y, Ohsugi M, Inabe K, Umehara T, Yoshida M, Kakei M, Kitamura T, Luo J, Kulkarni RN, Kahn CR, Kasai H, Cantley LC, Kadowaki T. Class IA phosphoinositide 3-kianse in pancreatic beta-cells controls insulin secretion by multiple mechanisms. Cell Metabolism 12(6):619-32, 2010.

86. Hinault C, Kawamori D, Liew CW, Maier B, Hu J, Keller S, Mirmira R, Scrable H, Kulkarni RN*. Delta 40 isoform of p53 controls beta-cell proliferation and glucose homeostasis in mice. Diabetes 60(4):1210-22, 2011. PMCID: PMC3064094

87. Kim W, Doyle ME, Liu Z, Lao Q, Shin Y-K, Carlson OD, Kim H-S, Thomas S, Napora JK, Lee EK, Moaddel R, Wang Y, Maudsley S, Martin B, Kulkarni RN, Egan JM. Cannabinoids inhibit insulin receptor signaling in pancreatic beta cells. Diabetes 60(4):1198-209, 2011. PMCID: PMC3064093

88. Lin W, Cao J, Liu J, Beshiri M, Fujiwara Y, Francis JM, Cherniack A, Geisen C, Blair LP, Zou M, Shen X, Kawamori D, Liu Z, Grisanzio C, Watanabe H, Minamishima Y, Zhang Q, Kulkarni RN, Signoretti S, Rodig SJ, Bronson RT, Orkin SH, Tuck DP, Benevolenskaya E, Meyerson M, Kaelin WG, Yan Q. Loss of the RBP2 histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1. Proc Natl Acad Sci 108(33):13379-13386, 2011. PMCID: PMC3158206

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89. Reiner T, Thurber G, Gaglia J, Vinegoni C, Liew CW, Upadhyay R, Kohler RH, Li L, Kulkarni RN, Benoist C, Mathis D, Weissleder R. Accurate measurement of pancreatic islet β-cell mass using a second-generation fluorescent exendin-4 analog. Proc Natl Acad Sci USA 108(31):12815-12820, 2011. PMCID: PMC3150928

90. Lopez X, Cypess A, Manning R, O’Shea S, Kulkarni RN, Goldfine AB. Exogenous insulin enhances glucose-stimulated insulin secretion in healthy humans independent of changes in free fatty acids. J Clin Endocrinol Metab 96(12)-3811-3821, 2011; PMID: 21956413. PMCID: PMC3232618

91. Rowland KR, Trivedi S, Wan K, Kulkarni RN, Holzenberger M, Robine S, Brubaker PL. Selective loss of glucagon-like-peptide-2-induced proliferative signaling in mice with conditional deletion of the intestinal epithelial insulin-like growth factor-1 receptor. Gastroenterology 141(6):2166-2175.e7. 2011; PMID:21925122.

92. Folli F, Okada T, Perego C, Gunton J, Liew CW, Akiyama M, D’Amico A, La Rosa S, Placidi C, Lupi R, Marchetti P, Sesti G, Hellerstein M, Perego L, Kulkarni RN*. Altered insulin receptor signalling and beta-cell cycle dynamics in type 2 diabetes mellitus. PLoS One 6(11): e28050, 2011 PMID:22140505. PMCID: PMC3227614

93. Halperin F, Lopez X, Manning R, Kahn CR, Kulkarni RN, Goldfine AB. Insulin augmentation of glucose stimulated insulin secretion is impaired in insulin resistant humans. Diabetes 61(2):301-309, 2012. PMID: 22275085 PMCID: PMC:3266415

94. Galkina E, Butcher M, Keller SR, Goff M, Bruce A, Pei H, Sarembock IJ, Sanders JM, Nagelin MH, Srinivasan S, Kulkarni RN, Hedrick CC, Lattanzio FA, Dobrian AD, Nadler JL, Ley K. Accelerated atherosclerosis in Apoe-/- mice heterozygous for the insulin receptor and the insulin receptor substrate-1. Arterioscler Thromb Vasc Biol 32(2):247-256, 2012 PMID: 22199371

95. Lee EK, Kim W, Tominaga K, Martindale JL, Yang X, Subaran SS, Carlson OD, Kulkarni RN, Akamatsu W, Okano H, Egan JM, Gorospe M. RNA-binding protein HuD controls insulin translation. Mol Cell 45(6):826-835, 2012. PMID: 22387028 PMCID: PMC3319250

96. Kebede M, Ferdaoussi M, Mancini A, Alquier T, Kulkarni RN, Walker MD, Poitout V. Glucose activates GPR40 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1. Proc Natl Acad Sci 109(7):2376-2381, 2012. PMID: 22308370 PMCID: PMC3289358

97. Kim W, Lao Q, Shin Y-K, Carlson OD, Lee EK, Gorospe M, Kulkarni RN, Egan JM. Cannabinoids induce pancreatic beta-cell death by directly inhibiting insulin receptor activation. Sci Signaling 20:5(216):ra23, 2012 PMID:22434934

98. Morioka T, Dishinger JF, Reid KR, Liew CW, Zhang T, Inaba M, Kennedy RT, Kulkarni RN*. Enhanced GLP-1 and sulphonylurea-induced insulin secretion in islets lacking leptin signaling. Mol Endocrinol 26(6):967-976, 2012. PMID: 22474124 PMCID: PMC3355538

99. Welters HJ, ElOuaamari A, Kawamori D, Meyer J, Hu J, Smith DM, Kulkarni RN. Rosiglitazone promotes PPAR-gamma dependent and independent changes in gene expression in mouse islets. Endocrinology 153(10):4593-4599, 2012 PMID:22807489 PMCID:PMC3512010

100. Negahdar M, Aukrust I, Johansson BB, Molnes J, Molven A, Matschinsky FM, Søvik O, Kulkarni RN, Flatmark T, Njolstad PR, Bjørkhaug L. GCK-MODY diabetes associated with protein misfolding, cellular self-association and degradation. Biochimica et Biophysica Acta 1822:1705-1715, 2012 PMID:22820548 PMCID:PMC3444650

101. Liew CW, Boucher J, Cheong JK, Vernochet C, Mallol C, Townsend K, Langin D, Kawamori D, Hu J, Tseng Y-H, Hellerstein MK, Farmer SR, Goodyear L, Doria A, Bluher M, Hsu SI-H, Kulkarni RN*. Ablation of TRIP-Br2, a novel regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance. Nature Medicine 19(2):217-226, 2013 PMID:23291629 PMCID:PMC3567215 doi:10.1038/nm.3056

102. Su D, Shukla AK, Chen B, Kim J-S, Nakayasu E, Qu Y, Aryal U, Weitz K, Clauss TRW, Monroe ME, CampII DG, Bigelow DJ, Smith RD, Kulkarni RN, Qian W-J. Quantitative Site-specific Reactivity Profiling of S-nitrosylation in Mouse Skeletal Muscle Using Cysteinyl Peptide Enrichment Coupled with

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Mass Spectrometry. Free Rad Biol and Med 57:68-78, 2013 PMID: 23277143 http://dx.doi.org/10.1016/j.freeradbiomed.2012.12.010

103. Aukrust I, Bjorkhaug L, Molnes J, Haas W, Gygi S, Sovik O, Flatmark T, Kulkarni RN, Njolstad P. SUMOylation of pancreatic glucokinase regulates its cellular stability and activity. J Biol Chem 288:5951-62, 2013. PMID:23297408 PMCID:PMC3581398

104. ElOuaamari A, Kawamori, D, Dirice E, Liew CW, Shadrach JL, Hu J, Katsuta H, Hollister-Lock J, Qian W-J, Wagers AJ, Kulkarni RN*. Liver-derived factors drive beta-cell hyperplasia in insulin resistant states. Cell Reports 3(2):401-410, 2013 10.1016/j.celrep.2013.01.007 PMID:23375376

105. Teo AK, Windmueller R, Tjora E, Johansson BB, Dirice E, Njosltad P, Raeder H, Kulkarni RN*. Derivation of human induced pluripotent stem cells from patients with maturity onset diabetes of the young. J Biol Chem 288:5353-5356, 2013 Epub Jan 10, doi/10.1074/jbc.C112.428979 PMID:23306198 PMCID:PMC3581399

106. Akiyama M, Liew CW, Lu S, Hu J, Martinez R, Hambro B, Kennedy RT, Kulkarni RN*. X-box binding protein 1 is essential for insulin regulation of pancreatic alpha-cells. Diabetes 62:2439-2449, 2013. PMID:23493568; PMCID:PMC3615023

107. Raeder H, Vesterhus M, ElOuamaari A, Paulo JA, McAllister FE, Liew CW, Hu J, Kawamori D, Molven A, Gygi SP, Njolstad PR, Kahn CR, Kulkarni RN*. Absence of diabetes and pancreatic exocrine dysfunction in a transgenic model of carboxy-ester lipase-MODY. PLoS One 8(4):e60229, 2013 PMID:23565203 PMCID:PMC3615023

108. Koh H-J, Toyoda T, Jung MM, Lee M-Y, Sleeman MW, Kulkarni RN, Musi N, Hirshman MF, Goodyear LF. Tribbles 3 mediates endoplasmic reticulum stress-induced insulin resistance in skeletal muscle. Nat Commun 4:1871, 2013 PMID:23695665 PMCID:PMC3707125

109. Negahdar M, Aukrust I, Molnes J, Solheim MH, Johansson BB, Sagen JV, Dahl-Jorgensen K, Kulkarni RN, Sovik O, Flatmark T, Njolstad PR, Bjorkhaug L. GCK-MODY diabetes as a protein misfolding disease: the mutation R275C promotes protein misfolding, self-association and cellular degradation. Mol Cell Endocrinol 382(1):55-65, 2014.. doi:pii: S0303-7207(13)00357-2. 10.1016/j.mce.2013.08.020. PMID:24001579

110. Raeder H, McAllister FE, Tjora E, Bhatt S, Haldorsen I, Hu J, Willems SM, Vesterhus M, ElOuaamari A, Liu M, Raeder MB, Immervoll H, Hoem D, Dimsevski G, Njolstad PR, Molven A, Gygi SP, Kulkarni RN. Carboxyl-ester lipase Maturity-Onset Diabetes of the Young is associated with development of pancreatic cysts and upregulated MAPK signaling in secretin-stimulated duodenal fluid. Diabetes 63(1):259-269, 2014. PMID:24062244 PMCID:PMC3868055

111. Dirice E, Kahraman S, Jiang W, ElOuaamari A, De Jesus DF, Teo AKK, Hu J, Kawamori D, Gaglia JL, Mathis D, Kulkarni RN*. Soluble factors secreted by T-cells promote beta-cell proliferation. Diabetes 63(1):188-202, 2014. PMID:24089508 PMCID:PMC3868047

112. Mezza T, Muscogiuri G, Sorice GP, Clemente G, Hu J, Pontecorvi A, Holst JJ, Giaccari A, Kulkarni RN*. Insulin resistance alters islet morphology in non-diabetic humans. Diabetes 63:994-1007, 2014. PMID:24215793 PMCID:PMC3931397

113. Winnay J, Dirice E, Liew CW, Kulkarni RN, Kahn CR. p85alpha deficiency protects beta-cells from ER stress-induced apoptosis. Proc Natl Acad Sci USA 111(3):1192-1197, 2014 PMID:24395790 PMCID:PMC3903202

114. Kilic G, Alvarez-Mercado AI, Zarrouki B, Opland D, Liew CW, Alonso LC, Myers MG Jr, Jonas JC, Poitout V, Kulkarni RN, Mauvais-Jarvis FM. The islet estrogen receptor-alpha is induced by hyperglycemia and protects against oxidative stress-induced insulin-deficient diabetes. PLoS One 9(2):e87941, 2014. PMID:24498408 PMCID:PMC3912162

115. Liew CW, Assmann A, Templin AT, Raum JC, Lipson KL, Rajan S, Hu J, Kawamori D, Lindberg I, Philipson L, Sonenberg N, Goldfine AB, Stoffers DA, Mirmira RG, Urano F, Kulkarni RN*. Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic beta-cells. Proc Natl Acad Sci USA 111:E2319-28, 2014. PMID:24843127 PMCID:PMC4050564

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116. Teo AK, Valdez I, Dirice E, Kulkarni RN*. Comparable generation of Activin-induced definitive endoderm via additive Wnt or BMP signaling in absence of serum. Stem Cell Rep 3:5-14, 2014. PMID:25068117 PMCID:PMC4110751

117. Hatanaka M, Maier B, Sims E, Templin A, Kulkarni RN, Evans-Molina C, Mirmira R. Palmitate induces mRNA translation and increases ER protein load in islet beta cells via activation of the mammalian target of rapamycin pathway. Diabetes 63:3404-3415, 2014 PMID:24834975 PMCID:PMC4171659

118. Liu S, Xi Y, Bettaieb A, Matsuo K, Matsuo I, Kulkarni RN, Haj F. Disruption of protein-tyrosine phosphatase 1B expression in the pancreas affects beta-cell function. Endocrinology, 155:3329-3338, 2014 PMID:24956127 PMCID:PMC4138572

119. Cannon CE, Titchenell PM, Groff DN, ElOuaamari A, Kulkarni RN, Birnbaum MJ, Stoffers DA. The polycomb protein, Bmi1, regulates insulin sensitivity. Mol Metabolism, 3:794-802, 2014 PMID:25379404 PMCID:PMC4216405

120. Xi Y, Liu S, Bettaieb A, Matsuo K, Matsuo I, Hosein E, Chahed S, Wiede F, Zhang S, Zhang ZY, Kulkarni RN, Tiganis T, Haj FG. Pancreatic T cell protein-tyrosine phosphatase deficiency affects beta cell function. Diabetologia 58:122-131, 2015 PMID:25338551 PMCID:PMC4258175.

121. Kahraman S, Dirice E, De Jesus DF, Hu J, Kulkarni RN*. Maternal insulin resistance and transient hyperglycemia impacts the metabolic and endocrine phenotypes of offspring. Am J Physiol Endocrinol Metab 307(10):E906-18, 2014. PMID: 25249504 PMCID:PMC4233258

122. Rao TN, Marks-Bluth J, Sullivan J, Gupta MK, Chandrakanthan C, Fitch SR, Ottersbach K, Jang YC, Piao X, Kulkarni RN, Serwold T, Pimanda JE, Wagers AJ. High-level Gpr56 expression is dispensable for the maintenance and function of hematopietic stem and progenitor cells in mice. Stem Cell Res 14(3):307-322, 2015. PMID:25840412; PMCID:PMC4439311

123. Al-Share QY, DeAngelis AM, Lester SG, Bowman TA, Ramakrishnan SK, Abdallah SL, Russo L, Patel PR, Kaw MK, Raphael CK, Kim AJ, Heinrich G, Lee AD, Kim JK, Kulkarni RN, Philbrick WM, Najjar SM. Forced hepatic over-expression of CECAM1 curtails diet-induced insulin resistance. Diabetes 64(8):2780-2790, 2015. PMID:25972571; PMCID:PMC4512217.

124. El Ouaamari A, Zhou J-Y, Liew CW, Shirakawa J, Dirice E, Gedeon N, Kahraman S, De Jesus DF, Bhatt S, Kim J-S, Clauss T, Camp D, Smith R, Qian W-J, Kulkarni RN*. Compensatory islet response to insulin resistance revealed by quantitative proteomics. J Proteome Res 14(8):3111-3122, 2015. PMID:26151086 PMCID:PMC4615688

125. Gupta MK, Teo AKK, Rao TN, Bhatt S, Kleinridders A, Shirakawa J, Takatani, T, Hu J, De Jesus DF, Windmueller R, Wagers AJ, Kulkarni RN*. Excessive cellular proliferation negatively impacts reprogramming efficiency of human fibroblasts. Stem Cells Transl Med 4(10):1101-1108, 2015. PMID:26253715; PMCID:PMC4572895

126. Lee Y-J, Liu C, Liao M, Sukhova GK, Shirakawa J, Abdennour M, Iamarene K, Andre S, Inouye K, Clement K, Kulkarni RN, Banks AS, Libby P, Shi G-P. Deficiency of FcεR1 increases body weight gain but improves glucose tolerance in diet-induced obese mice. Endocrinology 2015, Aug 21:2n20151184. PMID:26295369. PMCID:PMC4606759.

127. Bhatt S, Gupta MK, Khamaisi M, Martinez R, Gritsenko MA, Wagner BK, Guye P, Busskamp V, Shirakawa J, Valdez I, Wu G, Liew CW, El Ouaamari A, Dirice E, Takatani T, Keenan HA, Smith RD, Church G, Wagers AJ, Weiss R, Qian W-J, King GL, Kulkarni RN*. Preserved DNA damage checkpoint pathway protects from complications in long-standing type 1 diabetes. Cell Metabolism 22:239-242, 2015 PMID:26244933; PMCID:PMC4589213.

128. Dirice E, Kulkarni RN*. Harnessing immune cells to enhance β-cell mass in type 1 diabetes. J Invest Med 64(1):14-20, 2016. PMID:26755809

129. El Ouaamari A, Dirice E, Gedeon N, Hu J, Zhou J-Y, Shirakawa J, Hou L, Goodman J, Karampelias C, Qiang G, Boucher J, Martinez R, Gritsenko MA, De Jesus DF, Kahraman S, Bhatt S, Smith RD, Beer H-D, Jungtrakoon, P, Gong Y, Goldfine AB, Liew CW, Doria A, Andersson O, Qian W-J, Remold-O’Donnell E, Kulkarni RN*. SerpinB1 promotes pancreatic β-cell proliferation. Cell Metabolism 23(1):194-205, 2016. PMID:26701651 PMCID:PMC4715773

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130. Ghanem SS, Heinrich G, Lester SG, Pfeiffer V, Bhattacharya S, Patel PR, DeAngelis AM, Dai T, Ramakrishnan SK, Smiley ZN, Jung DY, Lee Y, Kitamura T, Ergun S, Kulkarni RN, Kim JK, Giovanucci DR, Najjar SM. Increased glucose-induced secretion of glucagon-like-peptide-1 in mice lacking the carcino-embryonic antigen-related cell adhesion molecule 2. J Biol Chem 291(2):980-988, 2016. PMID:26586918 PMCID:PMC4705415

131. Mezza T, Sorice GP, Conte C, Sun VA, Cefalo CMA, Moffa S, Pontecorvi A, Mari A, Kulkarni RN, Giaccari A. Beta cell sensitivity is linked to insulin/glucagon bi-hormonal cells in non-diabetic humans. J Clin Endocrinol Metab 101(2):470-475, 2016. PMID:26649619.

132. Singhal G, Fisher FM, Chee MJ, Tan TG, El Ouaamari A, Adams AC, Najarian R, Kulkarni RN, Benoist C, Flier JS, Maratos-Flier E. Fibroblast growth factor 21 (FGF21) protects against high fat diet induced inflammation and islet hyperplasia in pancreas. PLoS One 11(2):e0148252. PMID:26872145 PMCID:PMC4752212

133. Teo AKK, Lau HH, Valdez I, Dirice E, Tjora E, Raeder H, Kulkarni RN*. Early developmental perturbations in a human stem cell model of MODY5/HNF1B pancreatic hypoplasia. Stem Cell Rep 6(3):357-367, 2016. PMID:26876668; PMCID:PMC4788763

134. Dhawan S, Dirice E, Kulkarni RN, Bhushan A. Inhibition of TGF-beta signaling promotes human pancreatic beta-cell replication. Diabetes 65(5):1208-1218, 2016. PMID:26936060; PMCID:PMC4839200

135. Dirice E, Walpita D, Vetere A, Meier BC, Kahraman S, Hu J, Danick V, Burns SM, Gilbert TJ, Olson DE, Clemons PA, Kulkarni RN*2, Wagner BK*2. Inhibition of DYRK1A stimulates human beta-cell proliferation. Diabetes 65(6):1660-1667, 2016. PMID:26953159; PMCID:PMC4878416 (2Co-corresponding author).

136. Valdez IA, Dirice E, Gupta MK, Shirakawa J, Teo AKK, Kulkarni RN*. Pro-inflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent Ngn-3-activation. Cell Reports 15(3):460-470, 2016. PMID:27068459;PMCID:PMC4838491

137. Molven A, Hollister-Lock J, Martinez R, Njolstad PR, Liew CW, Weir GC, Kulkarni RN. The hypoglycemic phenotype is islet cell-autonomous on short-chain hydroxyl-CoA dehydrogenase (SCHAD) deficient mice. Diabetes 65(6):1672-1678, 2016. PMID:26953163

138. Softic S, Boucher J, El Ouaamari A, Krumpoch MT, Kleinridders A, Kulkarni RN, O’Neill BT, Kahn CR. Differential roles of insulin and IGF1 receptors in adipose tissue development and function. Diabetes 65(8):2201-2213, 2016. PMID:27207537; PMCID:PMC4955980

139. Takatani T, Shirakawa J, Roe MW, Leech C, Maier B, Mirmira RA, Kulkarni RN*. IRS-1 deficiency protects β-cells against ER-stress-induced apoptosis by modulating sXBP-1 stability and protein translation. Sci Reports 6:28177, 2016 PMID:27378176; PMCID:PMC4932502

140. Mezza T, Shirakawa J, Martinez R, Hu J, Giaccari A, Kulkarni RN*. Nuclear export of FoxO1 is linked to ERK signaling in β-cells lacking insulin receptors. J Biol Chem 291:21485-21495, 2016 PMID:27535223; PMCID:PMC5076820

141. Sakaguchi M, Fujisaka S, Cai W, Winnay JN, Konishi M, O’Neill B, Li M, Garcia-Martin R, Takahashi H, Hu J, Kulkarni RN, Kahn CR. Adipocyte dynamics and reversible metabolic syndrome in mice with an inducible adipocyte-specific deletion of the insulin receptor. Cell Metabolism 25(2):448-462, 2017. PMID:28065828; PMCID:PMC5304432

142. Shirakawa T, Fernandez M, Takatani T, ElOuaamari A, Jungtrakoon P, Okawa E, Zhang W, Yi P, Doria A, Kulkarni RN*. Insulin signaling regulates the FoxM1-CENPA-PLK1 pathway to modulate adaptive β-cell proliferation. Cell Metabolism 25(4):868-882,e5, 2017. PMID:28286049; PMCID:PMC5382039

143. Kawamori D, Shirakawa J, Liew CW, Hu J, Morioka T, Duttaroy A, Burkey B, Kulkarni RN*. GLP-1 signaling compensates for impaired insulin signaling in regulating β-cell proliferation in βIRKO mice. Diabetologia 60(8):1442-1453, 2017. PMID:28526921; PMCID:PMC5508991

144. Patti ME*, Goldfine AB, Hu J, Hoem D, Molven A, Goldsmith J, Schwesinger WH, La Rosa S, Folli F, Kulkarni RN*. Heterogeneity of proliferative markers in pancreatic β-cells of patients with severe hypoglycemia following Roux-en-Y gastric bypass. Acta Diabetologia 54(8):737-747, 2017 (*, co-corresponding authors). PMID:28512677; PMCID:PMC5515485

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145. Ghanem SS, Muturi HT, DeAngelis AM, Hu J, Kulkarni RN, Heinrich G, Najjar SM. Age-dependent insulin resistance in male mice with null detection of the carcinoembryonic antigen-related cell adhesion molecule 2 gene. Diabetologia 60(9):1751-1760, 2017. PMID:28567513; PMCID:PMC5709176

146. Dirice E, Ng R, Martinez R, Hu J, Wagner FF, Holson EB, Wagner BK, Kulkarni RN*. Isoform-selective inhibitor of histone deacetylase 3(HDAC3) limits pancreatic islet infiltration and protects female nonobese diabetic mice from diabetes. J Biol Chem 292(43):17598-17608, 2017. PMID:28860191; PMCID:PMC5663865

147. Shin HH, Han JH, Juhwan Y, SIM HJ, Park TJ, Siyoung Y, Lee EK, Kulkarni RN, Egan J, Kim W. Blockade of cannabinoid 1 receptor improves glucose responsiveness in pancreatic beta cells. J Cell and Mol Med, 22(4): 2337–2345, 2018. PMID:29431265; PMCID:PMC5867156

148. Inoue H, Shirakawa J, Togashi Y, Tajima K, Okuyama T, Kyohara M, Tanaka Y, Orime K, Saisho Y, Yamada T, Shibue K, Kulkarni RN, Terauchi Y. Signaling between pancreatic β-cells and macrophages via S100 calcium-binding protein A8 exacerbates β-cell apoptosis and inflammation. J Biol Chem 293(16): 5934–5946, 2018. PMID: 29496993; PMCID:PMC5912464

149. Kim C, Jeong DE, Heo S, Ji E, Rho JG, Jung M, Ahn S, Kim YJ, Kim YS, Nam SW, Kulkarni RN, Lee KB, Lee EK, Kim W. Reduced RNA-binding protein HuD in pancreatic neuroendocrine tumors lowers p27Kip1 levels linked to poor prognosis. J Pathol 246(2): 231–243, 2018; PMID:30014466; PMCID:PMC6150781

150. Jeong DE, Heo S, Han JH, Lee EY, Kulkarni RN, Kim W. Glucose controls the expression of the polyprimidine tract-binding protein 1 vis the insulin receptor signaling pathway in pancreatic β-cells. Mol Cells, 41(10): 909-916, 2018. PMID:30165730;PMCID:PMC6199568

151. Gupta M, DeJesus DF, Kahrman S, Valdez IA, Shamsi F, Yi L, Swensen AC, Tseng YH, Qian W-J, Kulkarni RN*. Insulin receptor mediated signaling regulates pluripotency markers and lineage determination. Mol Metab 18:153-163, 2018 PMID:30316806;PMCID:PMC6308035

152. Rao TN, Gupta MK, Softic S, Wang LD, Jang YC, Thomou T, Bezy O, Kulkarni RN, Kahn CR, Wagers AJ. Attenuation of PKCδ activity enhances metabolic activity and promotes expansion of blood progenitors. EMBO J, 37(24), 2018. PMID:30446598; PMCID:PMC6293338

153. ElOuaamari A, O-Sullivan I, Shirakawa J, Basile G, Zhang W, Rogers S, Thomou T, Xu S, Qiang G, Liew CW, Kulkarni RN*, Unterman T*. Forkhead box protein O1 (FoxO1) regulates hepatic serine protease inhibitor B1 (serpinB1) expression in a non-cell autonomous fashion. J Biol Chem 294(3):1059-1069, 2019. (*, co-corresponding authors). PMID:30459233; PMCID:PMC6341384

154. Ji Y, Sun S, Shreshta N, Darragh L, Shirakawa J, Xing Y, He Y, Carboneau BA, Kim H, An D, Ma M, Oberholzer J, Soleimanpur SA, Gannon M, Liu C, Naji A, Kulkarni RN, Wan Y, Kersten S, Qi L. Toll-like receptors 2 and 4 act as brakes to regulate adaptive β-cell mass expansion in diet-induced obesity. Nat Immunol 20(6):677-686, 2019. PMID:31110312; PMCID: PMC6531334

155. Jungtrakoon P, Shirakawa J, Buranasupkajorn P, Gupta MK, DeJesus DF, Pezzolesi MG, Panya A, Hastings T, Chaprasert C, Mendonca C, Kulkarni RN, Doria A. Loss-of-function mutation in thiamine transporter 1 in a family with autosomal dominant diabetes. Diabetes 68(5):1084-1093, 2019. PMID:30833467; PMCID: PMC6477897

156. Li Y, Tsai CF, Dirice E, Swensen AC, Chen J, Shi T, Gritsenko MA, Piehowski PD, Smith RD, Rodland KD, Atkinson MA, Kulkarni RN, Liu T, Qian WJ. A boosting to amplify signal isobaric labeling (BASIL) strategy for comprehensive quantitative phosphoproteomic characterization of amsll populations of cells. Anal Chem 91(9):5794-5801, 2019. PMID: 30843680; PMCID: PMC6596310

157. Dirice E, DeJesus DF, Kahraman Dirice S, Basile G, Ng RWS, El Ouaamari A, Teo AKK, Bhatt S, Hu J, Kulkarni RN*. Human duct cells are a source of β-cell reserve in the compensatory response to insulin resistance. JCI Insight 4(8) 2019. PMID:30996131; PMCID: PMC6538348

158. Dirice E, Kahraman S, De Jesus DF, El Ouaamari A, Basile G, Baker R, Yigit B, Piehowski PD, Kim M, Dwyer AJ, Ng RWS, Schuster C, Vethe H, Martinov T, Ishikawa Y, Teo AKK, Smith RD, Hu J, Haskins K, Serwold T, Qian W-J, Fife BT, Kissler S, Kulkarni RN*. Increased β-cell proliferation prior to immune-

46

cell invasion prevents progression of type 1 diabetes. Nat Metab 1(5):509-518, 2019. PMID:31423480; PMCID: PMC6696912

159. Ng NHJ, Jasmen JB, Lim CS, Lau HH, Krishnan GG, Kadiwala J, Kulkarni RN, Raeder H, Vallier L, Hoon S, Teo AKK. iScience 16:192-205, 2019. PMID:31195238; PMCID: PMC6562146

160. DeJesus DF, Zhang Z, Kahraman S, Brown N, Chen M, Hu J, Gupta MK, He C, Kulkarni RN*. m6A methylation regulates human islet biology and plays a role in the β-cell failure of type 2 diabetes. Nat Metab 1:765-774, 2019. PMID:

161. Loo LSW, Vethe H, Soetedjo AAP, Paulo JA, Jasmen J, Jackson J, Bjorlykke Y, Valdez IA, Vaudel M, Barsnes H, Gygi SP, Raeder H, Teo AKK, Kulkarni RN*. Dynamic protemcs profiling of human pluripotent stem cell-derived pancreatic progenitors. Stem Cells (accepted), 2019. PMID:

162. DeJesus DF, Orime K, Dirice E, Kaminska D, Wang C-H, Hu J, Mannisto V, Silva AM, Tseng YH, Pihlajamaki, Kulkarni RN*. NREP bridges TGF-β signaling and lipid metabolism in the epigenetic programming of NAFLD. J Clin Investigation (in revision).

163. Takatani T, Shirakawa J, Gupta MK, Lu S, Hu J, White MF, Kennedy RT, Kulkarni RN*. IRS-1 plays a dominant role in regulating pancreatic α-cell function. (in revision).

164. Gupta M, Veithe H, Softic S, Wagh V, Shirakawa S, Barsnes H, Vaudel M, Takatani T, Sakaguchi S, Martinez R, Hu J, Bjorlykke Y, Raeder H, Kulkarni RN*. Leptin signaling regulates protein synthesis and neuronal development in pluripotent stem cells. (submitted).

165. Pradas-Juni M, et al. A MAFG-lnc RNA axis links systemic nutrient abundance to hepatic glucose metabolism. (submitted).

166. Teo AKK, Gupta MK, Lau HH, Loo LSW, Lim CS, Mallard W, Gritsenko MA, Rinn J, Smith RD, Kulkarni RN*. Insulin receptor signaling regulates pluripotency, cell-fate commitment, ECM and homeostasis in hPSCs. (submitted).

Other peer-reviewed publications: 1. Kulkarni RN, Ghatei MA, Byfield P, Bloom SR. The effect of GLP-1 (7-36)NH2 and its fragments on

insulin release. Digestion 54:380-382, 1993. 2. Kulkarni RN*. Cells in focus: The islet beta-cell. Int J Biochem Cell Biol 36(3):365-371, 2004 PMID:

14687913 3. Hinault C, Hu J, Maier BF, Mirmira RG, Kulkarni RN*. Differential expression of cell cycle proteins

during ageing of pancreatic islet cells. Diabet Obes Metab 10 Suppl. 4:136-46. 2008 PMID: 18834441 4. Welters HJ, Kulkarni RN. Wnt signaling: relevance to beta cell biology and diabetes. Trends Endocrinol

Metab, 19(10):349-55 2008 PMID: 18926717 5. Kulkarni RN*. Uncoupling modifier genes from uncoupling protein 2 in pancreatic beta-cells. News and

Views, Endocrinology July 2009. PMCID: PMC 2703513 6. Liew CW, Holman A, Kulkarni RN*. The role of telomeres and telomerase in beta-cell regeneration.

Diabetes Obes Metab 11 (Suppl. 4): 21–9, 2009. PMID: 19817785 7. Assmann A, Hinault C, Kulkarni RN*. Growth factor control of pancreatic islet regeneration and function.

Ped Diabetes, 10(1):14-32, 2009. PMID: 18828795 PMCID: PMC2630373 8. Kawamori D, Welters HJ, Kulkarni RN*. (2010) Molecular pathways underlying the pathogenesis of α-

cell dysfunction. In: Islam MS, editor. Adv Experimental Medicine & Biology 654:421-445. 9. Kawamori D, Akiyama M, Hu J, Hambro B, Kulkarni RN*. Growth factor signaling in the regulation of

α-cell fate. Diabetes Obes Metab Suppl 1:21-30, 2011;PMID:21824253 10. Kulkarni RN*. Commentary: Identifying biomarkers of subclinical diabetes. Diabetes 61(8):1925-1926,

2012 PMID:22826312 PMCID: PMC3402306 11. Kulkarni RN*, Bernal-Mizrachi E, Garcia-Ocana A, Stewart AF. Perspective: Human beta-cell

proliferation and intracellular signaling: driving in the dark without a roadmap. Diabetes 61:2205-2213, 2012 PMID:22751699 PMCID: PMC3425429

12. Goldfine AB, Kulkarni RN*. Insulin modulation of beta-cell function: A translational journey from bench to bedside. Diabetes Obes Metab 14 Suppl 3:152-160, 2012 PMID:22928576

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13. Teo AK, Wagers AJ, Kulkarni RN*. New opportunities: harnessing induced pluripotency for discovery in diabetes and metabolism. Cell Metabolism Dec 3;18(6):775-91. doi:pii: S1550-4131(13)00336-7. 10.1016/j.cmet.2013.08.010. PMID:24035588 PMCID: PMC3858409

14. Bernal-Mizrachi E, Kulkarni RN, Scott DK, Mauvais-Jarvis F, Stewart AF, Garcia-Ocana A. Perspective: Human beta-cell proliferation and intracellular signaling Part 2: Still Driving in the Dark without a Roadmap. Diabetes 63:819-831, 2014. PMID:24556859 PMCID:PMC3931400

15. Mezza T, Kulkarni RN*. The regulation of pre- and post-maturational plasticity of mammalian islet cell mass. Diabetologia July 2014. PMID:24824733

16. De Jesus DF, Kulkarni RN*. Epigenetic modifiers of islet function and mass. Trends Endocrinol Metab 25:628-636, 2014 PMID: 25246382

17. Valdez I, Teo AKK, Kulkarni RN*. Cellular stress drives pancreatic plasticity. Science Transl Med 7(273):273ps2, 2015. PMID:25653218

18. Stewart AF, Hussain MA, Garcia-Ocana A, Vasavada RC, Bhushan A, Berbal-Mizrachi E, Kulkarni RN*. Human beta cell proliferation and intracellular signaling: Part 3. Diabetes 64(6):1872-1885, 2015. PMID:25999530; PMCID:PMC4439562.

19. Teo AKK, Gupta M, Doria A, Kulkarni RN*. Dissecting diabetes/metabolic disease mechanisms using pluripotent stem cells and genome editing tools. Mol Metabolism 4(9):593-604, 2015. PMID:26413465; PMCID:PMC4563028. doi. 10.1016/j.molmet.2015.06.007.

20. Shirakawa J, Kulkarni RN*. Novel factors modulating human β-cell proliferation. Diabetes Obes Metab 18:Suppl. 1:71-77, 2016. PMID:27615134; PMCID:PMC5021183

21. Mezza T, Cinti F, Cefalo CMA, Pontecorvi A, Kulkarni RN, Giaccari A. β-cell fate in human insulin resistance and type 2 diabetes: a perspective on islet plasticity. Diabetes 68(6):1121-1129, 2019. PMID:31109941

22. De Jesus DF, Kulkarni RN*. “Omics” and epi”-omics” underlying the β-cell adaptation to insulin resistance. Mol Metab 27S:S42-S48. 2019

Non-peer reviewed scientific or medical publications/materials in print or other media: Proceedings of meetings or other non-peer reviewed research publications 1. Shetty PS, Kurpad AV, Kulkarni RN & Vaz M. Thermogenic responses to norepinephrine in chronic

energy deficiency. Nestle Report: Basel, 33-42, 1988, pp 33-42. 2. Shetty PS, Kulkarni RN, Soares MJ, Kurpad AV, Piers LS, Vaz M & Jayachandra M. Effects of short-term

food supplementation on total energy expenditure and energy cost of physical activity of undernourished subjects. United Nations University Report: Tokyo, 1989.

Reviews, chapters, monographs, editorials 1. Shetty PS, Kulkarni RN, Piers LS, Kurpad AV, Vaz M, Soares MJ. Thermogenesis in chronic under

nutrition. In: Gopalan V, editor. Recent Trends in Nutrition. New Delhi: Oxford University Press: 1993. p. 35-48.

2. Kulkarni RN. Diabetes Mellitus. In: Bloom SR, ed. Toohey’s Medicine. 15th edition. London: Churchill Livingstone, 1995. pp 299-313.

3. Olmos G, Kulkarni RN, Haque M, MacDermot J. Imidazolines stimulate release of insulin from RIN 5AH cells independently from imidazoline-I1 and -I2 receptors. Ann N Y Acad Sci 763:374-376, 1995.

4. Kulkarni RN, Michael MD, Kahn CR. Tissue-specific knockout of insulin receptor tyrosine kinase. In: Accili D. ed. Genetic manipulation of receptor expression and function. New York, Wiley-Liss, 2000. pp. 129-154.

5. Kahn CR, Bruning JC, Michael MD, Kulkarni RN*. Knockout mice challenge our concepts of glucose homeostasis and the pathogenesis of diabetes mellitus. J Pediatr Endocrinol Metab 13 Suppl 6:1377-84, 2000 PMID: 11202213

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6. Kulkarni RN*, Kahn CR. Genetic Models of Insulin Resistance: Alterations in Beta-Cell Biology. In Habener JF, Hussain MA eds. Molecular Basis of Endocrine Pancreas Development and Function. Amsterdam, Kluwer Scientific, Vol. 11, 2001, pp 299-323.

7. Mauvais-Jarvis F, Kulkarni RN, Kahn CR. Knockout models are useful tools to dissect the pathophysiology and genetics of diabetes and insulin resistance. Clinical Endocrinol 57:1-9, 2002

8. Kulkarni RN*. Receptors for insulin and insulin-like growth factor-1 and insulin receptor substrate-1 mediate pathways that regulate islet function. Biochem Soc Trans 30(2):317-322, 2002 PMID: 12023872

9. Kulkarni RN*, Okada T. Tissue-specific targeting of the insulin receptor gene. Endocrine, 19:257-266, 2002 PMID: 12624425

10. Kulkarni RN*, Zisman A. Lessons for human diabetes from experimental mouse models. Curr Diab Rep 2(3):168-175, 2003 PMID: 12728643

11. Kulkarni RN*, Kahn CR. HNFs: linking the liver and pancreatic islets in diabetes. Science, 303:1311-1312, 2004 PMID: 14988544

12. Kulkarni RN*. New insights into the roles of insulin/IGF-I in the development and maintenance of beta-cell mass. Rev Endocr Metab Disord 6:199-210, 2005 PMID: 16151624

13. Kulkarni RN*. Insulin action in the islet beta-cell. In: Saltiel A., Pessin J., eds. Mechanisms of Insulin Action. Austin, TX, and New York: Landes Bioscience and Springer Science and Business Media, 2005. pp. 133-151.

14. Neubauer N, Kulkarni RN*. Molecular approaches to study control of glucose homeostasis. ILAR Vol. 47 (3):199-211, 2006 PMID: 16804195

15. Morioka T, Kulkarni RN*. Mechanisms for beta-cell formation in response to insulin resistance. US Endocrine Disease, I: 42-44, 2006.

16. Kulkarni RN*, Kahn CR. Ephs and ephrins keep pancreatic beta-cells connected. Cell 129:241-243, 2007 PMID: 17448984

17. Dirice E, Kulkarni RN*. Pathways regulating beta-cell regeneration in type 1, type 2 and gestational diabetes. In Kulkarni R.N., ed. Islet Cell Growth Factors. Austin, TX, and New York: Landes Bioscience and Springer Science and Business Media, 2011. pp 1-22.

18. Spiegel A, Carter-Su C, Taylor SI, Kulkarni RN. Mechanism of action of hormones that act at the cell surface. In Melmed S, Polonsky KS, Larsen PR, Kronenberg HM. Williams Textbook of Endocrinology. 12th edition. Philadelphia: Elsevier/Saunders, 2011. Pp. 62-82.

19. Kulkarni RN*. GIP: No longer the neglected incretin twin? Sci Transl Med 2:49ps47, 2010 DOI:10.1126/scitranslmed.3001027 PMID: 20844284

20. Morioka T, Kulkarni RN*. Pancreatic islet beta-cell failure in obesity. Chapter 11; In Ahima RS. Metabolic Basis of Obesity. New York: Springer Science, pp 199-217 2011,

21. Kawamori D, Kulkarni RN*. Molecular mechanisms modulating the intra-islet regulation of glucagon secretion. "Hypoglycemia / Book 2"; InTech (open-access) (ISBN 979-953-307-245-5), 2011.

22. Zhou, J.Y, Dann, G.P, Liew, C.W, Smith, R.D, Kulkarni , R.N, Qian, W.J. Unraveling Pancreatic Islet Biology by Quantitative Proteomics. Expert Rev Proteomics 8(4):495-504, 2011. PMCID: PMC21819304

23. Bhatt S, Kulkarni RN*. Chapter. Significance of organ crosstalk in insulin resistance and type 2 diabetes. In Karsenty G, ed. Translational Endocrinology of Bone: Reproduction, Metabolism, and the Central Nervous System. Waltham, MA: Elsevier/Academic Press. 2012. Pp. 199-220.

24. Teo AK, Kulkarni RN. Setting sail for glucose homeostasis with the AKAP150-PP2B anchor. EMBO J 31(20):3956-3957, 2012 PMID:22983555; PMCID: PMC3474931

25. Kulkarni RN*, Stewart AF. Summary of the Keystone Islet Workshop (April 2014): The increasing demand for human islet availability in diabetes research. Letter to the Editor: Diabetes 63(12):3979-3981, 2014 PMID:25414011; PMCID:PMC4238004.

26. Expanding treatment options for youth with type 2 diabetes: Current problems and proposed solutions. A white paper from the NICHD Diabetes Working Group. Diabetes Care 39:323-329, 2016. PMID:26908928; PMCID:PMC4764039

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27. Kahraman S, Okawa E, Kulkarni RN*. Is Transforming Stem Cells to Pancreatic Beta Cells Still the Holy Grail for Type 2 Diabetes? Curr Diab Reports 16(8):70, 2016

28. Shirakawa J, Kulkarni RN*. ERRγ: a new player in β-cell maturation. Cell Metabolism 23(5):765-767, 2016. PMID:27166940.

29. Shirakawa J, De Jesus DF, Kulkarni RN*. Exploring inter-organ crosstalk to uncover mechanisms that regulate β-cell function and mass. Eur J Clin Nutr March 15 2017 doi: 10.1038/ejcn.2017.13.PMID:28294170

30. Johansson BB, Fjeld K, El Jellas K, Gravdal A, Dalva M, Tjora E, Ræder H, Kulkarni RN, Johansson S, Njølstad PR, Molven A. Pancreatology 18(1):12-19, 2018. PMID: 29233499;

31. Gannon M, Kulkarni RN, Tse H, Mauvais-Jarvis F. Sex differences underlying pancreatic islet biology and its dysfunction. Mol Metab 15:82-89, 2018. PMID29891438: PMCID: PMC6066785.

32. Iliopoulos-Tsoutsouvas C, Kulkarni RN, Makriyannis A, Nikas SP. Fluorescent probes for G-protein-coupled receptor drug discovery. Exp Opin Drug Discov Sep 24, 1-15; doi.org/10.1080/17460441.2018.1518975; PMID 30249143

Books / Textbooks for the medical or scientific community 1. Kulkarni RN*. Editor, Islet Cell Growth Factors. (open-access) ISBN10:158706104X;

ISBN13:978158706104: Landes Bioscience, Eurekah.com. 2011 Theses:

MD : Kulkarni RN. Measurement of 24-hour energy expenditure in man using whole-body calorimetry. Bangalore University, 1990. pp 1-178

PhD : Kulkarni RN. The role of regulatory peptides in the control of β-cell function. University of London, 1996. pp 1-273

Narrative Report

My research is focused on investigating signalling pathways impacting growth and function of pancreatic islet cells, with the long-term goal of improving therapeutic approaches for the treatment of type 1 and type 2 diabetes and obesity-associated diabetes. I devote most of my time to research, with the rest spent in teaching and administrative responsibilities. The studies relate to investigating the two major signalling pathways in islets – the insulin/insulin like growth-factor-I and leptin pathways. The overall strategy is aimed at investigating the role of signalling proteins, activated by insulin, IGF-I or leptin receptors, in regeneration, growth, survival, secretory and synthetic functions of pancreatic islet cells in the context of type 1 and type 2 diabetes and in obesity-related diabetes. These studies will also provide a basis for exploring mechanisms that underlie the compensatory beta-cell response to insulin resistance and islet dysfunction that occurs in type 2 diabetes. The experiments have involved creation and phenotypic characterization of genetically engineered mouse models that have gain-of-function or loss-of-function mutations of specific proteins in the insulin/IGF-I signalling and leptin pathways in a tissue-specific manner. Different knockouts are examined for their role in glucose homeostasis using primary islets, beta or alpha cells and clonal beta-cell or alpha-cell lines derived from the knockouts (Nat Genetics 38(5):583-588, 2006; Proc Natl Acad Sci USA 104:8977-8982, 2007). I have identified a liver-derived secretory protein that promotes beta-cell proliferation by activating signalling proteins in the growth factor pathway in humans, mice and zebrafish and these findings have implications for developing therapeutic approaches to enhance functional beta-cell mass in humans with diabetes (Cell Reports 3(2):401-410, 2013; Cell Metabolism 23(1):194-205, 2016). We have also identified small molecules that can promote proliferation of human beta cells (Diabetes 65(6):1660-1667, 2016; Diabetes 65(5):1208-1218, 2016) and provide evidence for a role for pro-inflammatory cytokines in enhancing transdifferentiation of pancreatic ductal cells (Cell Reports 15(3):460-470, 2016). I am studying molecular interactions between proteins in the

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growth factor signalling pathway and p53, TRB3 (J Clin Invest 120(8):2876-2888, 2010) and PPAR-gamma and their roles in the regulation of mitochondria function, proinsulin processing and endoplasmic reticulum stress in islet cells (Diabetes 62:2439-2449, 2013; Proc Natl Acad Sci USA 111(22):E2319-28, 2014; Sci Reports 6:28177, 2016). These experiments will be complemented by rescuing the phenotypes through (1) re-expressing the “knocked out” protein, or (2) by expressing proteins with mutations in tyrosine moieties that are known to modulate specific signalling pathways, or (3) by expressing mutant proteins found in humans with leprechaunism. The studies aimed at examining the roles of insulin and IGF-I signalling in islet alpha-cell growth and function provide insights into understanding mechanisms that underlie hypoglycaemia (Cell Metabolism 9:350-361, 2009). The studies involving the leptin signalling pathway (J Clin Invest 117(10):2860-2868, 2007) will provide an understanding of the potential cross-talk between growth factor and leptin signalling in islets in the context of obesity.

We have identified Trip-Br2, a transcriptional co-regulator, in the regulation of adipocyte metabolism by modulating hormone sensitive lipase and beta adrenergic receptors (Nature Medicine 19(2):217-226, 2013). The up-regulation of TRIP-Br2 in visceral fat, not subcutaneous fat, in obese humans underscores its significance in the pathogenesis of obesity. An evolving area of interest includes understanding the role of growth factor signalling in the renewal and differentiation of embryonic stem (ES) cells and induced pluripotent stem (iPS) cells with the aim of studying mechanisms that underlie differentiation of pancreatic endocrine cells (Stem Cell Rep 3:5-14, 2014). We are particularly focusing on deriving iPS cells from skin fibroblasts from patients with type 1 and type 2 diabetes and Maturity Onset Diabetes of the Young (MODY) patients (J Biol Chem 288:5353-5356, 2013; Cell Metabolism 22:239-242, 2015; Stem Cells Transl Med 4(10):1101-1108, 2015; Stem Cell Reports 6(3):357-367, 2016) and establishing protocols to differentiate the iPS cells into insulin-secreting beta-like cells. In parallel studies, we are participating in experiments aimed at deriving cell types involved in complications secondary to diabetes (e.g. endothelial cells, podocytes, and pericytes). I have been a local administrative leader through roles as Director of the DERC Specialized Assay Center (2002-12) and Director of the Specialized Assay Core (2012-13) and the Fellowship Committee (2004-2014) and Associate Director of the induced Pluripotent Stem Cells (iPS) (20014-2017) Core of the DRC and the IACUC Committee (2004-2018) at Joslin Diabetes Center. I am currently the Associate Director of the DRC at Joslin. In addition, I now serve on the Faculty Promotions Committee (Department of Medicine, Brigham and Women’s Hospital, HMS) and Harvard-affiliated committees including Undergraduate Thesis and PhD Thesis Advisory Committees. I contribute to teaching by participating in the Cell Biology Course and the BBS Conduct of Science Course at Harvard University. In my own lab, I mentor post-doctoral fellows and visiting scientists in weekly one-one meetings and informal meetings in the lab, and supervise research assistants and summer and rotation students. I also organize Boston-Ithaca Islet Group Meetings, attended by ~100 junior and senior faculty, post-doctoral fellows, and students from up to 15 islet research labs in the Northeast—especially geared to benefit young investigators in presenting research and developing collaborations. I contribute to educational symposia organized by the Joslin Diabetes Center, the ADA, and the JDRF in the areas of diabetes and obesity and in symposia organized by HSCI in the area of stem cells. I also co-wrote a White paper submitted to the NIH, JDRF, and ADA—based on a “call to action” workshop I led at the April 2014 Keystone Symposium—that is an educational document advocating for greater access to human islets in diabetes research. It was signed by 25 senior Faculty nationwide (Diabetes, 63(12):3979-3981, 2014). In summary, my contributions are focused on investigating the molecular mechanisms and signalling pathways that underlie the pathogenesis of type 1 and type 2 diabetes and obesity-associated diabetes, teaching students,

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mentoring post-doctoral fellows and students to foster scientific thinking, and participating in educational activities to promote scientific awareness.