Mar – Apr 2020 RESEARCH BULLETIN

Narwhal: One of the Most Contiguous Vertebrate Genomes

At a recent Advances in Genome Biology and Technology meeting, Dr. Martin Nweeia, lecturer in the Department of Restorative Dentistry and Biomaterials Sciences, announced a de novo narwhal assembly to participants as The Narwhal Genome Initiative announced its collaborative work with the University of California Davis Genome Center, the Broad Institute of MIT and Harvard, the Wellcome Sanger Institute, Pacific Biosciences, Dovetail Genomics, the University of Maryland Medical School, the Smithsonian Institution, and the Ocean Genome Legacy at Northeastern University.

Nweeia is searching for genetic clues to biologic and evolutionary questions of narwhal tooth development, expression, and morphology. “We are creating the library and instruction manual for the narwhal, and today brings us to one of the most complete and contiguous vertebrate genomes. Answers to our biologic questions are looming in these strands of DNA, and we remain committed to finding them.”

Nweeia’s recent book with the Smithsonian Institute, Narwhal: Revealing An Arctic Legend won the William Mills Award, given to the best published book on the Poles in a two- year period. Nweeia’s

scientific investigation of the narwhal began nearly 20 years ago.

KOTA RECEIVES NIH-NIAMS AWARD

Satya Kota, PhD, instructor in Oral Medicine, Infection and Immunity, received a NIH-NIAMS R01 award, “Systematic Elucidation of Allele Specific Proteome at Imprint Control Regions (ICRs).”

Imprinting disorders are rare, epigenetic disorders that encompass multiple tissues and many of them lead to growth, endocrine and neurological defects with lasting affects during the lifespan of the affected individual. In this project, Dr. Kota aims to elucidate the proteome on parental alleles of ICRs to understand how parent-of-origin expression is maintained during development. Findings from this study will lead to a greater understanding of the type of trans protein factors at ICRs and will provide mechanistic details into their roles in cis regulation. Overall, these studies will lead to deeper understanding of monoallelic gene regulation that underlie multi-tissue pathologies of associated disorders and may help inform the design of novel therapeutic and diagnostic approaches for these disorders.

Dr. Kota is also a recipient of career development grant from NIH-NIAMS that is aimed to gain insights into epigenetic regulation and its key targets during skeletal development and progenitor cell differentiation.

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PUBLICATIONSDEVELOPMENTAL BIOLOGYAllareddy V, Bruun R, MacLaine J, Markiewicz M, Ruiz R, Miller M. Orthodontic preparation for secondary alveolar bone grafting in patients with complete cleft lip and palate. Oral and Maxillofacial Surgery Clinics of North America 2020; Feb 22.

Allareddy V, Shusterman S, Ross E, Palermo V, Ricalde P. Dentofacial orthopedics for the cleft patient: The Latham approach. Maxillofacial Surgery Clinics of North America 2020; Feb 17.

Farooq Rai M, Brophy R, Rosen V. Toward a comprehensive understanding of the molecular biology of meniscus pathology: lessons learned from translational studies and mouse models. Journal of Orthopedic Research 2020; Feb 18.

Gan W, Dai X, Dai X, Xie J, Yin S, Zhu J, Wang C, Liu Y, Guo J, Wang M, Liu J, Hu J, Quinton R, Ganem N, Liu P, Asara J, Pandolfi P, Yang Y, He Z, Gao G, Wei W. LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control. Nature Cell Biology 2020; Feb 3.

Papakyrikos A, Arora M, Austin C, Boughner J, Capellini T, Dingwall H, Greba Q, Howland J, Kato A, Wang X, Smith T. Biological clocks and incremental growth line formation in dentine. Journal of Anatomy 2020; Apr 7.

Parashar K, Schulte F, Hardt M, Baker O. Sex-mediated elevation of the specialized pro-resolving lipid mediator levels in a Sjögren’s syndrome mouse model. FASEB Journal 2020; Apr 11.

Kantaputra P, Dejkhamron P, Intachai W, Ngamphiw C, Kawasaki K, Ohazama A, Krisanaprakornkit S, Olsen B, Tongsima S, Ketudat Cairns J. Juberg-Hayward syndrome is a cohesinopathy, caused by mutation in ESCO2. European Journal of Orthodontics 2020; Apr 7.

Kim Y, Sundrud M, Zhou C, Edenius M, Zocco D, Powers K, Zhang M, Mazitschek R, Rao A, Yeo C, Noss E, Brenner M, Whitman M, Keller T. Aminoacyl-tRNA synthetase inhibition activates a pathway that branches from the canonical amino acid response in mammalian cells. Proceedings of the National Academy of Science USA 2020; Apr 6.

Muruganandan S, Ionescu A, Sinal C. At the crossroads of the adipocyte and osteoclast differentiation programs: Future therapeutic perspectives. International Journal of Molecular Science 2020; Mar 26;21(7).

Papakyrikos A, Arora M, Austin C, Boughner J, Capellini T, Dingwall H, Greba Q, Howland J, Kato A, Wang XP, Smith T. Biological clocks and incremental growth line formation in dentine. Journal of Anatomy 2020; Apr 7.

Richard D, Liu Z, Cao J, Kiapour A, Willen J, Yarlagadda S, Jagoda E, Kolachalama V, Sieker J, Chang G, Muthuirulan P, Young M, Masson A, Konrad J, Hosseinzadeh S, Maridas DE, Rosen V, Krawetz R, Roach N, Capellini T. Evolutionary selection and constraint on human knee chondrocyte regulation impacts osteoarthritis risk. Cell 2020; Mar 26.

Volloch V, Olsen BR, Rits S. AD “Statin”: Alzheimer’s disorder is a “fast” disease preventable by therapeutic intervention initiated even late in life and reversible at the early stages. Annals of Integrative Molecular Medicine 2020;2(1):75-89.

Xu L, Li Y. A molecular cascade underlying articular cartilage degeneration. Current Drug Targets 2020; Feb 14.

Zhou T, Gao B, Fan Y, Liu Y, Feng S, Cong Q, Zhang X, Zhou Y, Yadav P, Lin J, Wu N, Zhao L, Huang D, Zhou S, Su P, Yang Y. Piezo1/2 mediate mechanotransduction essential for bone formation through concerted activation of NFAT-YAP1-B-catenin. Elife 2020; Mar 18;9.

KRAKOW AWARDSWilliam Arden, DMSc 2021 Endodontics

Dr. Arden is working on “Assessing the Neurotoxicity of Endodontic Sealers” with Dr. Jennifer Gibbs at HSDM.

Ozge Erdogan, DMSc 2022 Oral Biology

Dr. Erdogan is working on “Exploring Host-Microbiome Interactions in Symptomatic and Asymptomatic Irreversible Pulpitis Using Quantitative Proteomics” with Dr. Jennifer Gibbs at HSDM and Dr. Markus Hardt from the Forsyth Institute.

Ha Bin Park, MMSc 2022 Endodontics

Dr. Park is working on “Electrokinetic Flow: Novel Technology for the Enhanced Release of Dentinal Growth Factors” with Drs. Jennifer Gibbs at HSDM and Jongyoon Han at the Massachusetts Institute of Technology.

Howard Yoon, MMSc 2022 Endodontics

Dr. Yoon is working on “Evaluation of Resveratrol as an Adjunct for Direct Pulp Capping in Reparative Dentin Formation and Post-Operative Pain Suppression in Mice” with Dr. Jennifer Gibbs at HSDM.

Dr. Alvin Arlen Krakow, widely known as the leading force behind the establishment of Harvard School of Dental Medicine’s postdoctoral program in endodontics, passed away in 2018. His lasting legacy at the School includes funding the annual Krakow Research Awards.

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Davis C, Hakim M, Choi D, Behrman D, Israel H, McCain J. Early clinical outcomes of arthroscopic management of the failing alloplastic temporomandibular joint prosthesis. Journal of Oral and Maxillofacial Surgery 2020; Jan 15.

Durrani I, Ji Y, Peacock Z. Do speakers fully disclose potential conflicts of interest in oral and maxillofacial surgery? Journal of Oral and Maxillofacial Surgery 2020; Mar 18.

Ji Y, Keith D. Clinical trials of rare benign pathologies in oral and maxillofacial surgery. Journal of Oral and Maxillofacial Surgery 2020; Feb 18.

Liberton D, Verma P, Almpani K, Fung P, Mishra R, Oberoi S, Senel F, Mah J, Huang J, Padwa B, Lee J. Craniofacial analysis may indicate co-occurrence of skeletal malocclusions and associated risks in development of cleft lip and palate. Journal of Developmental Biology 2020; Jan 28;8(1).

Padwa B, Yu J. Discussion: Challenges in the successful reconstruction of cleft lip and palate: Managing the nasomaxillary deformity in adolescence. Plastic Reconstructive Surgery 2020;145(3):604e-605e.

Patel N, Ji Y, Donoff R. Clinical productivity and medicare payments among female and male oral and maxillofacial surgeons. Journal of Oral and Maxillofacial Surgery 2020; Jan 7.

ORAL HEALTH POLICY AND EPIDEMIOLOGYAlqaderi H, Tavares M, Al-Mulla F, Al-Ozairi E, Goodson J. Late bedtime and dental caries incidence in Kuwaiti children: A longitudinal multilevel analysis. Community Dentistry and Oral Epidemiology 2020; Feb 20.

Chido-Amajuoyi O, Agaku I, Onwuliri C, Shete S. Industry-sponsored antismoking advertisements in low-income countries. Lancet Global Health 2020; Apr;8(4):e485-e486.

Choi S, Simon L, Barrow J, Palmer N, Basu S, Phillips R. Dental practice integration into primary care: A microsimulation of financial implications for practices. International Journal of Environmental Research and Public Health 2020 Mar 24;17(6).

Kasper J, Mulye A, Doobay-Persaud A, Seymour B, Nelson B. Perspectives and solutions from clinical trainees and mentors regarding ethical challenges during global health experiences. Annals of Global Health 2020; Mar 26;86(1):34.

Nedjat-Haiem F, Cadet T, Ferral A, Ko E, Thompson B, Mishra S. Moving closer to death: understanding psychosocial distress among older veterans with advanced cancers. Supportive Care in Cancer 2020; Apr 12.

Simon L, Karhade D, Tobey M. Oral health status of hospitalized patients with type 2 diabetes. Diabetes Spectrum 2020; Feb;33(1):58-65.

Vardavas C, Nikitara K. COVID-19 and smoking: A systematic review of the evidence. Tobacco Induced Diseases 2020;18:20.

Yansane A, Tokede O, Walji M, Obadan-Udoh E, Riedy C, White J, Kalenderian E. Burnout, engagement, and dental errors among U.S. dentists. Journal of Patient Satisfaction 2020; Apr 3.

This image is from Dr. Meghan McDougall’s, MMSc20 orthodontics research study, “The cornea and true horizontal as non-radiographic replacements for the cranial base in Steiner’s Cephalometric Analysis: A proof of concept study.”

ORAL MEDICINE, INFECTION AND IMMUNITYAlmazyad A, Li C, Woo SB. Benign alveolar ridge keratosis: Clinical and histopathologic analysis of 167 cases. Head and Neck Pathology 2020; Mar 16.

Boisen I, Mos I, Lerche-Black E, Juul A, Bräuner-Osborne H, Blomberg Jensen M. Heterozygous mutation (Q459R) in the calcium-sensing receptor gene causes familial hypocalciuric hypercalcemia 1 (FHH1). Journal of Clinical Endocrinology Metabolism 2020; Apr 1;105(4).

Bor B, Collins A, Murugkar P, Balasubramanian S, To T, Hendrickson E, Bedree J, Bidlack F, Johnston C, Shi W, McLean J, He X, Dewhirst F. Insights obtained by culturing Saccharibacteria with their bacterial hosts. Journal of Dental Research 2020 Feb 19.

Fantozzi P, Treister N, Shekar R, Woo SB, Villa A. Corrigendum to “intralesional triamcinolone acetonide therapy for inflammatory oral ulcers.” Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 2020; 128(5):485-490.

Fantozzi P, Villa A, Antin J, Treister N. Regression of oral proliferative leukoplakia following initiation of ibrutinib therapy in two allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplantation 2020; Apr 9.

Gupta A, Villa A, Feldman S, Citow B, Sroussi H. Site and sex-specific differences in the effect of vitamin D on human papillomavirus infections: analyses of NHANES 2009-2014. Sex Transmission and Infection 2020; Mar 31.

Kameda M, Abiko Y, Washio J, Tanner A, Kressirer C, Mizoguchi I, Takahashi N. Sugar metabolism of Scardovia wiggsiae, a novel caries-associated bacterium. Frontiers in Microbiology 2020;11:479.

Root S, Wee N, Novak S, Rosen C, Baron R, Matthews B, Kalajzic I. Perivascular osteoprogenitors are associated with trans-cortical channels of long bones. Stem Cells 2020; Feb 13.

Villa A, Sankar V, Bassani G, Johnson L, Sroussi H. Dexamethasone solution and dexamethasone in Mucolox for the treatment of oral lichen planus: a preliminary study. Oral Surgery Oral Medicine Oral Pathology Oral Radiology 2020; Mar 24.

Weinstein B, Pham C, Nguyen T. The reverse palatal pedicle graft (RPPG) for maxillary molar palatal recessions: Two case reports. Clinical Advances in Periodontics 2020; Feb 19.

Wilbert S, Mark Welch J, Borisy G. Spatial ecology of the human tongue dorsum microbiome. Cell Reports 2020; Mar 24;30(12):4003-4015.e3.

Yarom N, Hovan A, Bossi P, Ariyawardana A, Jensen S, Gobbo M, Saca-Hazboun H, Kandwal A, Majorana A, Ottaviani G, Pentenero M, Nasr N, Rouleau T, Lucas A, Treister N, Zur E, Ranna V, Vaddi A, Barasch A, Lalla R, Cheng K, Elad S. Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - Part 2: Honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.Supportive Care in Cancer 2020; Feb 13.

ORAL AND MAXILLOFACIAL SURGERY Azoulay-Avinoam S, Bruun R, MacLaine J, Allareddy V, Resnick C, Padwa B. An overview of craniosynostosis craniofacial syndromes for combined orthodontic and surgical management. Oral and Maxillofacial Surgery Clinics of North America 2020; Feb 17.

Buch K, Peacock Z, Resnick C, Rothermel H, Kaban L, Caruso P. Regional differences in temporomandibular joint inflammation in patients with juvenile idiopathic arthritis: a dynamic post-contrast magnetic resonance imaging study. International Journal of Oral and Maxillofacial Surgery 2020; Jan 31.

Chen Y, Zhang J, Han Y, Troulis M, August M. Benign pediatric jaw lesions at Massachusetts General Hospital over 13 years. Journal of Oral and Maxillofacial Surgery 2020; Feb 5.

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DMD STUDENTS RECEIVE RESEARCH HONORSCongratulations to the DMD students who received honors in research, or honors in global and community health for completing a rigorous research project and presentation to Dr. Francesca Gori, Dr. Shigemi Nagai, and Ms. Jane Barrow.

Alex Cruz, DMD21Cruz completed, “Access to Hospital-Based Adult Special Needs Dental Care” with mentor Dr. Nalton Ferraro for honors in research.

David Danesh, DMD20Danesh completed, “Risk and Protective Factor Framework Analysis to Inform an Oral Health Education Program for La Casona Indigenous Community in Coto Brus, Costa Rica” with mentor Dr. Brittany Seymour for

honors in global and community health.

Ryan Lisann, DMD20Lisann completed, “Framework for Analyzing Protective and Risk Factors for Caries Development Designed for La Casona Indigenous Community in Coto Brus, Costa Rica” with mentor Dr. Brittany Seymour for honors in global and community

health.

HSDM FORSYTH RESEARCH ACADEMY GRADUATES

Dr. Nora Alhazmi joined the HSDM Forsyth Research Academy DMSc program in 2017. In her second and third years of the Program, she worked with research mentor, Dr. Eric Liao at Massachusetts General Hospital, on her thesis entitled, “Requirement of Wnt Modulator R-spondin3 in Craniofacial

Morphogenesis and Dental Development.” Alhazmi reported, “My experience in the Research Academy has allowed me to practice novel research technology and helped me explore various areas of basic science research. The opportunity of pursuing my DMSc at Harvard has allowed me to explore ideas that have prepared me for my academic career. After graduation, I will join King Saud bin Abdulaziz University for Health Sciences in Saudi Arabia, as an assistant professor.”

Dr. Ali Alaqla also joined the HSDM Forsyth Research Academy DMSc program in 2017. After lab rotations at HSDM and the Forsyth Institute, he chose to join the Xiaozhe Han Laboratory in the Department of Immunology at the Forsyth Institute. He completed his thesis work, “Toll Like Receptors TLRs Stimulation of Bio Cells

Expansion and Function” under the mentorship of Han. “I had a memorable time during my journey at Harvard that I will always treasure. The amount of scientific exposure that I received throughout the program was unique and well-delivered. I was fortunate to learn different molecular and histological methods which allowed me to open my eyes to promising research areas that I will continue to explore in my future research and academic career.” After graduation, Alaqla will join the College of Dentistry at King Saudi bin Abdulaziz University for Health Sciences in Saudi Arabia.

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ROSEN RECEIVES NIH-NIAMS AWARD

Vicki Rosen, PhD, interim dean and professor and chair of Developmental Biology, received a subcontract award from Boston Children’s Hospital for an NIH-NIAMS R01 award, “Cfp1 Action in Cartilage.” Dr. Rosen is the co-investigator and Dr. Diana Carlone, instructor in Pediatrics at Boston Children’s Hospital, is principal investigator.

Transcription factors and signaling molecules are key modulators of cartilage development, with alterations in either resulting in skeletal anomalies. Dr. Carlone has identified Cfp1 as a factor required for cartilage formation. Results from this study will determine whether and how Cfp1 controls transcription factors and signaling molecules during cartilage development, which may impact our therapeutic approach to correct skeletal defects.

Jennie Marinucci, DMD20Marinucci completed, “Exploring the Relationship Between Adverse Childhood Experiences and Oral Health” with mentor Dr. Erin Dunn for honors in global and community health.

Laurel Martinez, DMD20Martinez completed, “Piezo Mechanosensory Channels Control Centriole Engagement via Calcium Signaling” with mentor Dr. Hao Wu for honors in research.

Kelly Suralik, DMD20Suralik completed, “Effect of Fabrication Method on Fracture Strength of Interim Fixed Dental Prosthesis Restorations” with mentor Dr. Sang Lee for honors in research.

Kristen Sweeney, DMD20Sweeney completed, “Fibrous Dysplasia and McCune Albright Syndrome: Understanding the Mechanisms of Disease Development and Progression Over Time” with mentor Dr. Leonard Kaban for honors in global and community health.

Amy Yu, DMD20Yu completed, “Developing an Outcomes-Based Strategic Plan for Long-Term Evaluation of a Novel Global Oral Health Curriculum for Dental Students” with mentor Dr. Brtittany Seymour for honors in global and community health.

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A PUBLICATION OF THE OFFICE OF RESEARCHMalcolm Whitman, PhD Associate Dean for Basic Science

Yingzi Yang, PhD Associate Dean for Translational Research

Dawn M. DeCosta Editor and Layout

Heather M. Denny Editing

Lia Sgourakes Editing

Ashley SimmonsEditing

QUESTIONS/COMMENTS?

HSDM Office of Research188 Longwood Avenue, REB 404Boston, Massachusetts 02115617-824-0715dawn_decosta@hsdm.harvard.edu

PUBLICATIONS CONT. RESTORATIVE DENTISTRY AND BIOMATERIALS SCIENCESBlicher B, Lucier Pryles R. Endodontic pain management: Preoperative, perioperative, and postoperative strategies. Compendium of Continuing Education in Dentistry 2020;41(4):242-243.

Negreiros W, Jamjoom F, Gallucci G, Hamilton A. Designing a complete-arch digital trial tooth arrangement for completely edentulous patients by using an open-source CAD software program: A dental technique. Journal of Prosthetic Dentistry 2020; Apr 4.

Nweeia M, Damas J, Shiue L, Sandoval N, Vedala S, Hall S, Ho S, Ghurye J, Sadowski L, Tallon L, Sisneros N, Kingan S, Korlach J, Lewin H. An improved de novo genome assembly of the narwhal (Monodon monoceros). Advances in Genome Biology and Technology February 2020; 223.

Nweeia M. 2019. ‘Inuit Qaujimajatuqangit’ in Richard W (ed)., Contributions from the field prepared for between sea and glacier: Greenland in a changing world, International Polar Institute Press, Hanover, New Hampshire; ASC-Smithsonian Institution, Washington, DC, pp 205-206.

Wittneben J, Gavric J, Sailer I, Buser D, Wismeijer D. Clinical and esthetic outcomes of two different prosthetic workflows for implant- supported all-ceramic single crowns - 3 year results of a randomized multicenter clinical trial. Clinical Oral Implants Research 2020; Feb 3.

Yamakami S, Guenka R, Palma D, Ohyama. Dental remineralization therapies for early caries. Journal of Cosmetic Dentistry 2020; 35(4):96-105.

This is a collaborative project funded by the American Dental Education Association entitled, “Dental Key: An Innovative, Online Clinical Lab Manual.”

The goal of this project is to improve clinical dental education by providing video demonstrations, illustrations, and step-by-step, best-practice instructions for basic dental procedures through a modern, intuitive, internet-based platform. The project aims to increase the utilization of modern technology in dental education to embrace the generational shift toward online learning. Ultimately, it is the hope this project will serve as a means of standardizing and democratizing dental education globally.

Photographed in the front row, left to right are faculty mentors, Dr. Supattriya Chutinan and Dr. Hiroe Ohyama. Top row, left to right are: Karen He, DMD21, Alice Li, DMD23, Leela Breitman, DMD21, Emily Van Doren, DMD22, and Jennifer Lee, DMD21.

AMERICAN DENTAL ASSOCIATION AWARD