Dr. GUNARETNAM (GUNA) RAJAGOPAL

PERSONAL DETAILS Citizenship: British (United States Permanent Resident) Marital Status: Married (Dr. Khaw Lake Ee)

CONTACT DETAILS

Global Head – Computational Sciences, Discovery Science, Janssen Pharma R&D 410 George Street, New Brunswick, NJ 08901 Office: 908-927-2773 grajagop@its.jnj.com The Simons Center for Systems Biology Institute for Advanced Study Einstein Drive, Princeton, NJ 08540 Office: (609) 734 8325 grajagopal@ias.edu

EMPLOYMENT HISTORY

VP & Global Head of Computational Sciences, Discovery Science, 10/2013, Janssen Pharma R&D (a J&J company).

VP & CIO – Research, Informatics and External Innovation, 6/2012 – 9/2013, Janssen Pharma R&D (a J&J company)

Executive Director (Bioinformatics), Chief Information Officer, 9/2007 – 6/2012 – Cancer Institute of New Jersey, Robert Wood Johnson Medical School, USA

Adjunct Professor, Radiation Oncology, 9/2009 – present, Robert Wood Johnson Medical School

Executive Director, 6/2006 – 8/2007 – Bioinformatics Institute, Singapore

Deputy Executive Director, 7/2001 - 5/2006 – Bioinformatics Institute, Singapore

Assistant Director of Research, 7/1996 – 6/2001, Cavendish Laboratory, University of Cambridge

Fellow & Director of Studies (Physics, Mathematics), 9/1997 – 6/2001, Jesus College, Cambridge

Postdoctoral Research Associate, Theory of Condensed Matter Group, 4/1994 – 6/1996, Cavendish Laboratory, University of Cambridge

Visiting Research Fellow, 9/1993 – 3/1994, School of Physics, Georgia Tech, Atlanta, Georgia, USA

Postdoctoral Research Associate, 9/1991 – 8/1993, Cavendish Laboratory, University of Cambridge

Director's Research Assistant, 9/1987 – 8/1991, School of Physics, Georgia Tech USA

Lecturer and Head of Physics, 6/ 1986 – 8/1987, Prime College, Kuala Lumpur, Malaysia

Lecturer in Physics, 1/1984 – 5/1986, Damansara College, Kuala Lumpur, Malaysia

Physics Instructor, 6/1981 – 12/1983, University of Malaya, Kuala Lumpur, Malaysia

EDUCATION

Ph.D. Physics, Georgia Institute of Technology, December 1991

M.S. Physics, Georgia Institute of Technology, December 1989

M.Sc. in High Energy Physics, University of Malaya, August 1984

B.Sc.Ed. Physics/Mathematics/Education, University of Malaya, August 1981

EXPERTISE

Total Informatics Strategy – helping bring better therapies to market for the benefit of patients –At Janssen, I have developed and am implementing a integrative strategy encompassing capabilities in IT/HPC, Informatics, Bioinformatics, Computational & Systems Biology and Genomics/Genetics to support and advance the R&D agenda throughout the R&D pipeline. To this end we have an overarching role across ALL of our therapeutic areas (Neuroscience, Oncology, Immunology, Cardiovascular Disease and Metabolism, Infectious Disease and Vaccines as well as supporting the small and large molecule centers of excellence. This involves collecting, storing, managing, annotating

and integrating data generated within and outside our company during our discovery, biomarker, pre/post PoC, drug safety, systems/clinical pharmacology and clinical trials. Our team is leading an effort to build a patient data warehouse to facilitate effective, efficient and secure use of our clinical data coupled with data from research to guide patient stratification, biomarker discovery and personalized therapies. The massive data sets are analyzed using a global network of HPC and cloud computing resources to help our researchers make meaningful use of the derived information and informed decisions on optimal strategies to maximize productivity.

Integrative Genomics – advancing Personalized and Precision Medicine – In partnership with basic and clinical researchers at CINJ/the Robert Wood Johnson Medical School, Princeton University, Rutgers University, the University of Medicine and Dentistry of New Jersey and the Institute for Advanced Study, I helped develop the computational and data analytical infrastructure to support genomic analysis of microarray and next generation sequencing data. The goal was to identify and characterize molecular factors whose deregulation give rise to the disease phenotype. As part of an international collaboration, I am involved in using WGS of multi-generational family exhibiting Li-Fraumani Syndrome to identify the relevant genetic structural variants that give rise to ‘genetic anticipation” in these families. My team has also executed WES, RNA-Seq and CHIP-Seq studies mainly in the areas of Skin/Breast/Prostate/Pancreatic Cancer, Leukemia stem cells, G-quad inhibition on cell lines, autism and auto-immune diseases such as IBD/Chron’s disease.

Translational Informatics – Linking Bench & Bedside - I lead a team working at the interface of quantitative biology, disease biology, medicine and population sciences to integrate & analyze data generated from diverse sources to address fundamental problems in discovering and developing therapies and bring them to market for the benefit of patients.. Before joining industry, in the Biopolis and New Jersey, I have been a PI/co-PI in a number of research grants linking experimental and quantitative approaches to address basis and translational research problems focused on Cancer Biology, Cancer Biomarker Discovery and Stem Cell Biology at the Biopolis/Singapore, the Institute for advanced Study in Princeton and the Cancer Institute of New Jersey.

Computational/Systems Biology - Large-scale Systems-Level Computational Modeling Of signaling pathways - I have applied the theoretical/computational tools and techniques to study signaling pathway in cancer, stem cell fate decisions, and linking aging and cancer. A quantitative understanding the disruption of cellular processes is critical if one wants to obtain a deeper conceptual understanding of the mechanisms that can give rise to disease as it allows an efficient way to guide the search of better drug targets and associated mechanism of action This work is done in partnership with colleagues within our therapeutic areas, and the Simons Center for Systems Biology at the Institute for Advanced Studies in Princeton.

Cyber-infrastructure Development, Deployment, Management & Application to Real-world Problems - I have been responsible for planning, building and managing such a complex cyber-infrastructure at the University of Cambridge and the Biopolis in Singapore. In Cambridge, I helped set up and run the Cambridge High Performance Computing Facility – a multi-department funded shared facility with IBM, Hitachi and

SGI. In Singapore, I chaired the IT cyber-infrastructure steering committee that worked with various government agencies and multi-national companies to develop, deploy and manage the cyber-infrastructure and services that support 3000 researchers located in 5 public and 8 private/pharma research laboratories collocated in the Biopolis. At CINJ, I built and supported the cyber-infrastructure in partnership with the University of Medicine and Dentistry of New Jersey to support basic, clinical and translational research to facilitate and support collaborations within CINJ and with external partners in academia, hospitals and the pharmaceutical industry in New Jersey.

RESEARCH ACTIVITY

At Janssen Pharma R&D

Drug Discovery - I lead a multi-disciplinary global team of physicists, mathematicians, HPC experts, computational biologists, statisticians, bioinformatics specialists and wet lab scientists. Our mission is to work with researchers within and outside our company to generate, evaluate and translate biomedical data into drug targets that lead to transformational, safe and effective medicines. To this end, my team is heavily engaged in deploying bioinformatics, machine learning and cutting-edge computational modeling and simulations techniques. Our in silico activities are complemented and experimentally validated by wet lab capabilities within the team utilizing stem cell, molecular genetics, gene editing, Imaging, Next Generation Sequencing and Omics technologies.

Big Data Analytics – My team is responsible for supporting the computational analytics needs of partners within our five therapeutic areas within Janssen and with external pre-competitive national/international initiatives involving Janssen scientists. This includes deploying our bioinformatics, computational and systems biology and machine learning expertise in support of basic, clinical and translational programs aligned with and addressing the evolving needs of Janssen scientists

High Performance Computing – we have developed and deployed HPC capabilities in support of our drug discovery and development mission by using internal expertise and building strong partnerships with INTEL and major supercomputing facilities in the U.S.A., the EU and Asia.

Before joining Janssen

My research was focused on three areas: (a) the understanding of how individual genetic profiles influence response to pathogens and therapies (b) identifying better targets for multi-factorial diseases by using systems and network pharmacology and (s) using NGS to study the genetics of complex diseases such as cancer, auto-immune and neurodegenerative diseases to guide the search for more effective biomarkers and therapies. To this end, my efforts were focused on developing integrative, quantitative techniques that help identify and characterize the genetic variations that distinguish the normal and diseased state.

Projects at the Institute for Advanced Study (Princeton) & The Cancer Institute of New Jersey - We have initiated a number of projects involving collaborations with academia, the biomedical community and the pharmaceutical industry:

transMED - aims to develop and deploy the latest web technologies, cyber-infrastructure and informatics capabilities to deploy an interoperable EMR to link physicians, patients within CINJ, the RWJ Medical School and the RWJ Hospital in New Brunswick with the ultimate goal of linking to CINJ’s Network hospitals throughout New Jersey. The goal is to collect, share and analyze population data (including, but not limited to, genomic and clinical data) to aid our ongoing efforts in cancer prevention, control and treatment. In addition, the data collected could be used (after appropriate ethical and IRB review) as a basis for collaborations and/or partnerships with pharmaceutical and biotech companies located within the state of New Jersey.

Computational Analysis of Genetic Variation: (With Prof. Arnold Levine, IAS; Dr. Chang Chan CINJ; Dr. Elke Market, CINJ; Dr. Gurinder Agrwal, CSHL) – Statistical inference of haplotypes from genotypes is a highly non-trivial task, which has spawned intensive recent research. The group has be on deploying an entropy-based method based on mutual information theory on massively parallel computers for efficient selection of structural variations and functionally characterize their role in disease initiation and progression. We are also working on developing new tools and techniques to (a) the analysis of differential gene expression arising as a result of genetic variation and (b) how polymorphisms influence signal transduction.

Network Pharmacology (Prof. Arnold Levine, Dr. Alexi Vazquez, CINJ, IAS, Dr. Eric Perakslis (J&J) – Using tools and techniques from the statistical physics of networks, we will probe data sets collected in the course of the drug discovery process to identify combination of drugs that can target a number of nodes in signaling and regulatory pathways that collectively are more sensitive and specific to control that actions of these pathways.

Next Generation Sequencing for Transcriptomics and Human Genetic Variation Study (with Profs. Arnold Levine, Lorna Rodriguez & The CINJ Precision Medicine Initiative) – we are leading the bioinformatics effort to design appropriate experiments and analyze data generated from next generation sequencing technologies in projects related to differential gene expression, whole genome/exome sequencing to map driver/passenger mutations, copy number variation etc. The goal is to identify key molecular players in cancer initiation/progression leading to optimal selection of treatment protocols and facilitate practice of personalized medicine. We use the entire range of NGS experiments to analyze data collected from normal/disease and germline tissue to elucidate disease causing driver mutations and susceptibility genes.

Projects Completed at the Bioinformatics Institute, Singapore

Developing Mathematical & Computational techniques for Stochastic Chemical Kinetics: (With Postdoctoral associate Dr. The Yu Kai and research associates Mr. Li Bin). A crucial

component of our project is the ability to quantitatively replicate the chemical kinetics occurring in mesoscopic systems such as that within the cell. We are developing mathematical and computational techniques to incorporate stochasicity into our pathway models, to quantify the effects of noise on system-level properties. The modeling framework resulting from this effort is being applied to the projects below.

Program Driver for Cancer Biology Initiative - Control and regulation of p53: (a) Imaging and Modeling of the p53-Hdm2 Feedback Loop: Role of Activator-Inhibitor Motifs in regulation of cellular processes; (b) A Systems Biology Approach to Elucidating the Role of the P38 MAPK Pathway and its Interactions with the p53 Mediated Cell Cycle Control Checkpoints in Tumor Suppression. (With Ph.D. student Mr. Mark Phong of Eli Lilly Systems Biology Singapore, Dr. Christopher Taylor of Lilly System Biology Singapore, Dr. Xiang Yi at Eli Lilly USA and Prof. Sir David Lane’s Group at IMCB, Singapore.). (a) Recently, Lahav et. al. (Nature Genetics, 36, 147, 2004) reported results of damped oscillations of p53/mdm2 proteins in individual living cells when subject to stress. They found that p53 was expressed in a series of discrete pulses after DNA damage. Their main conclusion is that the p53-MDM2 feedback loop generates a “digital” clock that releases well-timed quanta of p53 proteins until damage is repaired or the cell dies. Our aim, through a combination of experiments and quantitative modeling, is to verify these observations and to elucidate the mechanism that gives rise to the “digital pulses”. (b) To study the role of p38 MAPK as a tumor suppressor (a collaboration with Eli Lilly) we plan to: (1) To collect and annotate data related to developing a comprehensive map of the p38 MAPK pathway and its role in p53 mediated cell cycle control for the purposes of building a computational model that accurately describes the signal transduction process; (2) To formulate an appropriate mathematical and computational framework describing the simplified network topology of the p38 MAPK pathway and the p53 cell cycle response to genotoxic shock and DNA damage; (3) To validate the accuracy and veracity of the quantitative model through bench biology experiments on model cell lines enhancing the model iteratively; (4) Expansion from single cell model to cell population model. The experimental work will involve lab work in Lilly facilities in Singapore and Indianapolis. Furthermore, together with experimental collaborators within and outside Singapore (specifically Prof. Sir David Lane’s and Prof. Arnold Levine’s Groups) we have built and maintain a curated p53 KnowledgeBase (p53.bii.a-star.edu.sg) that is available to the whole community

Program Driver for Clinical Biomarker Initiative – Discovering and validating biomarkers for gastric cancer: (With Prof. Sir David Lane (IMCB), Prof. Yeoh KH (Medicine/NUS), Prof. S. Itoh (Oncology Research Institute), Prof. Edison Liu (GIS), Dr. Jeffery Hill(BII), Dr. Henry Yang(BII)) The primary focus of the Clinical Biomarkers Discovery Group is to collaborate with the international community in the International Cancer Biomarker Consortium (ICBC). This international consortium, led by the Prof. Lee Hartwell (Fred Hutchinson Cancer Research Institute in Seattle, USA) involves teams from Singapore, China, USA, France, Mexico, Korea and Taiwan etc. The goal is to discover biomarkers, which will be validated by the clinical collaborators that are invaluable for their potential discriminatory power in molecular classification of disease (diagnosis), in predicting clinical outcome (prognosis) and response to drugs (therapy). The Singapore national effort, with an initial focus on gastric cancer, is led by Prof. Sir

David Lane of the Institute of Molecular and Cell Biology, and will involve scientists from the Genome Institute of Singapore, Singapore Oncology Research Institute, and the Proteomics Facility at the Department of Biological Sciences (DBS) in the National University of Singapore and the Clinical School at the National University Hospital. I am responsible for the planning, deployment and management of the cyber-infrastructure and informatics/analysis platform that integrate data generated from the different institutions involved in an efficient, cost-effective and secure manner. To aid the coordination of this national/international effort, we are building a Gastric Cancer Knowledgebase that will contain actively curated biomedical information on all aspects of gastric cancer.

Program Driver for Stem Cell Biology Initiative - Identifying Intestinal Adult Stem Cells and Imaging Epithelial Migration: (Flagship project within the Singapore-MIT Alliance (SMA) in collaboration with Prof. Paul Matsudaira,Whitehead Institute (WI), Biology and BioEng, MIT, Dr. Walter Hunziker IMCB, Dr. Mahatavan GIS, Prof. Bing Lim Harvard Medical School, Prof. Birgit Lane at the Center for Molecular Medicine and SMA-MIT Scholars Wang Zhengyuan and Lee Seok Yoon) - To work within the SMA Computational and Systems Biology Initiative to pursue the following aims: (1) to use a combination of expression/proteomics and bioinformatics to identify specific stem cell markers which will facilitate their in vivo study via high-resolution real-time imaging of live tissues; (2) to identify the factors that regulate aspects of the behavior of stem cells such as the process of asymmetric division and differentiation etc. ultimately leading to a deeper understanding of the nature of “stemness”; (3) to develop quantitative models to explore how a gradient of Wnt morphogens along the crypt-villus axis in the small intestine can regulate proliferation and differentiation status as epithelial cells migrate from the crypt to the tip of the villus; (4) to elucidate the mechanism of epithelial cell migration in the epithelium of the small intestine of the Zebra fish using real-time high-resolution in vivo imaging of live tissue. To this end we will work closely with our experimental collaborators to obtain and analyze the data they collect to build quantitative models. This work is funded by a three year S$450K Singapore-MIT Alliance Grant jointly awarded with Prof. Matsudaira. The data obtained, together with all publicly available data on adult stem cells, will be collected and curated in a Stem Cell KnowledgeBase (stemcell.bii.a-star.edu.sg) that will be available to the whole community as part of theSingapore Stem Cell Consortium.

Modeling Mechanotransduction - A Systems Biology Approach to Elucidate the Role of Adhaerens Junctions and Tight Junctions as Mechanotransducers in Regulating Cell Proliferation. (With AGS Scholar Lim Tong Seng, Prof. Lim Chwee Teck (BioEng, NUS), Prof. Paul Matsudaira (WI, Biology and BioEng, MIT) and Prof. B. Lane, Center for Molecular Medicine, Singapore) – Mechanotransduction or the translation of mechanical forces into biochemical signals; plays an important role in the regulation of cellular activities. How cells sense external forces and integrate these forces at the molecular level to produce coordinated responses is an open question. In particular, the mechanism by which mechanical stimuli regulate cell proliferation is a subject of great controversy and a resolution to this issue has wider implications both for the fundamental understanding of cell biology and within a clinical context. To this end, we are investigating specific classes of proteins found in tight junctions and adhaerens junctions, which are specialized cell-cell contacts that play an important role in regulating cellular activities.

This project aims to test the hypothesis that specific members of the tight and adhaerens junction proteins act as mechanotransducers for regulating cell proliferation when quiescent epithelial cells in culture are subjected to mechanical stimuli. This work is funded by a three year S$600K Singapore Biomedical Research Council Grant.

Modeling Differential Gene Expression: A Systems Biology Approach to Elucidate the Frequency Decoding of GnRH Signals that Governs the Differential Expression of Mammalian Gonadotropin Subunit Genes. (With AGS Scholar Stefan Lim and Dr. Philippa Melmlud (DBS, NUS)): Luteinizing and follicle-stimulating hormones (LH and FSH) are gonadotropic hormones synthesized in the pituitary gonadotropes. They share a common a-subunit but contain a unique b-subunit that confers physiological specificity. LH and FSH directly stimulate gonadal growth and steroidogenesis. Therefore regulation of the precise levels of each hormone is critical to correct reproductive functioning. The hypothalamic GnRH regulates both hormones, and variations in its pulse frequency are associated with the differential effects on each of the three subunits. The mechanism by which gonadotropes decode varying gonadotropin-releasing hormone (GnRH) pulse frequencies and translate them into differential gene expression is unknown. It is the goal of this project to resolve this issue through an integrative approach involving a fusion of biological, genetic, computational and mathematical techniques. Understanding the molecular mechanisms that control gonadotropin biosynthesis holds great potential for the clinical treatment of a variety of reproductive disorders. The knowledge gained in the resolution of this problem will also contribute to a deeper conceptual understanding of the mechanisms governing differential expression of genes in general, which is the cornerstone of developmental biology. This work is funded by a three year S$800K Singapore Biomedical Research Council Grant.

Modeling Cross-talk between RhoGTPase and MAP Kinase Signaling Pathways: (With Research Associate Ang Boon Keong and Dr. Ong Siew Hwa (IMCB)) – The objective of this experimental/theoretical collaboration is to elucidate the function of Rho proteins and their regulators in various physiological processes given the importance of Rho GTPase signaling networks in development. We have initially focused on experimentally characterizing a specific Rho GAP protein, ArhGAP9, and its interactions with MAP kinases such as Erk2 and p38. We aim to show how actin remodeling can be regulated through the interaction of ArhGAP9 and the MAP kinases, cross-talking between the Rho GTPase and MAP kinase signaling pathways. The long term goal is to study experimentally and via bioinformatics and structural modeling how the formation of multi-protein complexes through the different domains present in GTPase regulators such as ArhGAP9 allows for the spatial and temporal coordination of different signaling pathways.

TEACHING EXPERIENCE

At the Robert Wood Johnson Medical School – supervised MD/PhD and PhD candidates, MD/PhD graduate lectures in bioinformatics and Genomics, short course on the use of bioinformatics and computing in biomedical research (to researchers and clinicians). With my team of computational biologists and bioinformatics specialists and biostatisticians conducted weekly “clinics” for clinicians and researchers on effective use of genomic and statistical techniques in experimental design of Omics studies in support of their research programs.

At the Bioinformatics Institute (BII), Singapore: supervised five PhD Scholars in Systems Biology and Bioinformatics as part of the Singapore-MIT Alliance; conducted postgraduate lectures/training for Tsinghua/Beijing University; at the national University f Singapore, gave lecture graduate courses in Computational Biology, Molecular Modeling, Mathematical/Systems Biology, Systems Biology of Cancer/Stem Cell; supervise MSc/PhD research projects in bioinformatics and computational/systems biology; lead study sessions on mathematical methods applied to biological problems; designed and implemented a MSc graduate program in Bioinformatics/Computational Biology. I was the external examiner for Physics PhD at the University of Cambridge.

At the University of Cambridge, UK: supervised a M. Phil. student, co-supervised seven Ph.D. students at the Cavendish Laboratory and three PhD students at Imperial College, London; lectured a Part II undergraduate physics course (Theoretical Physics I/II), and Part III course, ``Supercomputing in Physics"; lectures on high performance computing, biological physics and electronic structure theory; supervised Literature Reviews and Part III projects, Part II Quantum Mechanics, Solid State Physics, Thermal Physics, Systems, Part III Solid State Physics, Part IB Advanced Physics and Mathematics for IA and IB (Natural Science).

At the Georgia Institute of Technology, USA: Lectured freshman and sophomore Engineering Physics courses.

At the University of Malaya, Prime College and Damansara College, Malaysia: Physics Instructor/lecturer.

At the Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, USA, Rutgers University: Graduate lectures in Cancer Systems Biology, Bioinformatics and Computational Biology.

MANAGEMENT RESPONSIBILITIES

In the United States

At Janssen Pharma R&D (a J&J company): I am responsible for overseeing a team divided into five groups: Translational Informatics, Computational & Systems Biology, High Performance Computing, External Innovation and R&D IT. We support the evolving cyber-infrastructure/eData capture, Informatics, Big Data analytics, needs of researchers and clinicians throughout Janssen. I am a member of the therapeutic, functional area, Pharma R&D and R&D Operations senior leadership team. I am also a member of CINJ’s External Advisory Board for their Precision Medicine Initiative.

At the Cancer Institute of New Jersey (CINJ): I am responsible for all matters concerning computing – both for research, clinic and for corporate needs. I am setting up the Cancer Informatics Core facility from scratch. As Executive Director (Bioinformatics), I am responsible for building up Clinical and Bioinformatics capabilities to supporting ongoing basic, clinical, population sciences, translational research as well as postgraduate education for the CINJ community and its partners. I am responsible for the development, deployment and smooth operation of cyber-infrastructure and services to meet the evolving needs of the CINJ user

community. I was the Chair of the Electronic Medical Record Implementation Committee and Co-Chair of the Steering Committee: responsible for deploying and integrating a Electronic Medical Record system across the Cancer Institute of New Jersey, the Robert Wood Johnson Hospital and the Robert Wood Johnson Medical School. I am also member of the Clinical Enterprises Committee that oversees all clinical operations at the CINJ: responsible for providing advise on Informatics and IT/security issues relating to clinical operations.

I am a member of various internal advisory committees for overseeing CINJ Core facilities: Biostatistics Core, Microarray Core, Sequencing Core and Tissue Analytic Services.

Member of the Executive Council for the Cancer Institute of New Jersey: this is the key leadership committee that is chaired by the Director which meets weekly to manage the affairs of the Institute.

Member of the Scientific Council for the CINJ/Rutgers University/Princeton University Cancer Consortium: responsible for providing advise on scientific computing, biomedical informatics for inter-institutional collaborations.

Member of the DIMACS Executive Council, (2008 - 2012 ): Efficient, effective and secure access to and analysis of health data is THE central problem in health care informatics with serious implications for the economics of health care delivery, basic, clinical and translational research and in the prevention of disease. We are working with DIMACS to provide to tools and expertise to address one of the key challenges in the medical arena and am co-organizer of the “DIMACS/CINJ Working Group on Electronic Medical Records” (http://dimacs.rutgers.edu/Workshops/WGMedicalRecords/) and “Algorithmic Medical Decision Making: Leveraging Heterogeneous Data Sources for Quantifying Risk” Workshop ()http://dimacs.rutgers.edu/Workshops/QuantifyingRisk/).

At the Institute for Advanced Study: Conduct research in the areas of Computational/Systems Biology focused on the genetic variations in the human genome that give rise to complex diseases (such as cancer) and provide advice on all matters concerning computing needs of the Institute.

At the American Association for Cancer Research (AACR): chair the Bioinformatics Subcommittee for the AACR – NCI - FDA Cancer Biomarkers Collaborative. The subcommittee will explore current thinking from academia (i.e. the Cancer Bioinformatics Grid, caBIG) and industry on the role of informatics in cancer biomarker discovery. Its mandate is to map out and where possible, make recommendations on “best practices” in the use of bioinformatics tools and cyber-infrastructure resources and services in facilitating the discovery, validation, qualification and clinical deployment of diagnostic biomarkers for cancer,

In Singapore:

At the Bioinformatics Institute: set up the Institute from scratch in July 2001. Mission of the BII encompasses research in bioinformatics and computational biology, post-graduate education, IT and application support for the biomedical user community in Singapore and cyber-infrastructure development at the national level. The BII is the central national resource for

biomedical computing for the biomedical research community. My responsibilities include setting up and overseeing the management, research, biomedical computing support and post-graduate education activities of the Institute. Program driver for the Cancer Biology, Clinical Biomarkers and Stem Cell Initiatives that links experimental and quantitative modeling involving researchers within and beyond the Biopolis to address key biomedical questions in cancer and stem cell biology and to coordinate the building of a Web based knowledgebase to advance R&D in these areas. I was the Executive Director, responsible for providing the scientific and administrative leadership for the Institute.

Cross Institution responsibilities: Chairman of the Joint Management Committee overseeing the BII-NUS Postgraduate Program in Bioinformatics. Planned and implemented a graduate program in Bioinformatics involving 2 years of course work and academic and industrial attachment.

Research Council Responsibilities: Chairman of the IT Steering Committee for the Biomedical Research Council and Co-Chair of the One-north IT steering Committee responsible for planning, implementing and managing the outsourced cyber-infrastructure and services for the new science park, the Biopolis (Project SELECT). The Biopolis (www.one-north.com) is a physical co-location of public and private research institutes and biotech companies that will leverage on each other to advance biomedical research and development and exploit the results of the research for wealth creation. I direct the Project Team which is responsible for formulating, managing the tender process and the implementation of infrastructure and services. Member of the BMRC/NMRC Grant Evaluation Committee (2006-2009).

National Cyber-infrastructure development responsibilities: member of the Steering Committee for the Singapore National Grid Initiative whose goal is to aggregate national computing resources to effectively and efficiently address the needs of academia, industry and the medical community. To build up the expertise to accomplish this challenging task, I initiated the Singapore BioMed Grid (BMG) Project (in collaboration with similar Grid projects in the US and Europe). The main focus is to develop and implement grid-based middleware and application software of interest to the biomedical community to advance research and development in the public and private sector. We work very closely with companies such as Intel Sun and HP as well as the US national supercomputing centers (NCSA, PNNL and SDSC) to share expertise in developing grid computing for the biomedical user community. We are founding members of international collaborations in grid computing such as the PRAGMA Consortium and the GELATO Federation.

At the University of Cambridge, United Kingdom:

Cross-Department Responsibilities: Coordinator and member of management committee of the Cambridge High Performance Computing Facility (1994-2001); management of the day to day operation of the University of Cambridge High-Performance Computing Facility; providing technical advice to the user community within the University on all aspects of high performance computing; enhancement of supercomputing resources by preparing grant applications to funding bodies.

Cavendish Laboratory, University of Cambridge: Lecturer in Part II/Part III courses in Theoretical Physics and Computational Physics; Part III Physics Examiner for the 1998/1999 and 1999/2000 academic years.

EPSRC Research Council Responsibilities: Member of the EPSRC "Computational Partial Differential Equations" Panel (1998-2001). I refereed grant applications for EPSRC and HEFCE/JREI, the Welcome Trust and for joint MRC/DFG projects involve advanced computing in Biomedical research.

Jesus College: Elected member of Jesus College Governing Council (1998). Elected to the Mastership Committee (April 2000).Elected to the College Development Committee (July 2000). Director of Studies for Physics and Mathematics for Natural Scientists in Jesus College (1997-2001).

CONSULTANTCIES/SCIENTIFIC BOARDS

Grant reviewer for NIH, NSF, AACR, EU (ESF), UK (MRC, EPSRC, CRUK), Germany (DFG), Singapore (ASTAR) and Japan (MOE, JSI). Served as a member of external review boards for governments of Singapore, Ireland, UK and Malaysia.

Informatics Consultant for the Johnson & Johnson Centacor (Pharma arm of J&J):

Informatics Consultant for the Scientific Board for Novartis AG: Reviewed ongoing informatics activities throughout Novartis’s global R&D organizations, 2009 – 2012

Informatics Consultant for Daiichi Sankyo: Reviewed ongoing informatics activities throughout their global R&D organizations, 2010 – 2012

Program Grant Reviewer for Science Foundation Ireland, 2009 – present

Advisor, University of Malaya Medical Faculty, 2010 – present

Advisor, Cancer Research Foundation , Malaysia, 2008 - present

External Review Board, Personalized Medicine, Rutgers Cancer Institute of New Jersey, 2012 – present.

Scientific Advisory Board, IMEC, Belgium 2014 - present

Member of the European Commission Panel of Experts, Digital Agenda for Europe, 2014 - present

COMPUTATIONAL EXPERTISE

I have published research that used large scale computing to address challenge problems in computational chemistry, biology and physics. I am now focused on transferring the techniques and algorithms developed to understand problems in computational/systems biology and genetics (especially the use of NGS to advance drug discovery and development). As part of our Biomedical Grid initiative in Singapore I have been directing the year long training of grid engineers (53 trained with government funding), building a operational test-bed for biomedical

applications and developing new code to run over the grid cyber-infrastructure that links geographically distributed computing and data resources.

HONORS & AWARDS

Distinguished Visiting Professor, Ministry of Science and Technology, Malaysia (2010); Informatics Consultant (Advisor) for Norvatis (2009 -201 ); Johnson & Johnson (2008 - ); Daiichi Sankyo (2010 -2012 ); Special Merit Pay Allowance, University of Cambridge, (1991-1996, 1999-2004); Elected Fellow of Jesus College (1997); Awarded National Science Foundation (USA) scholarship to attend Supercomputing Summer School at the Pittsburgh Supercomputing Centre (June 1990); Director's Research Assistantship, School of Physics, Georgia Tech, (1987-1991); Appointed Junior Associate of the ICTP Trieste, Italy, (1986-1989).

GRANTS AWARDED

1. US$11.7M support from the Robert Wood Johnson University Hospital to design,

deploy and operate/manage an Oncology based EMR, 2009-2011.

2. Jointly awarded US$1.500M for Bioinformatics support for NIH Challenge grants,

2009 as co-PI in grants awarded to scientists at CINJ and RWJMS.

3. US$3M grant from State of New Jersey for building Computational, Systems Biology

and Bioinformatics capability at the Cancer Institute of New Jersey, 2007-2010

4. US$12M grant from the Robert Wood Johnson Foundation, as co-investigator in

population sciences study of cancer prevention, control and survivorship.

5. S$1.800M BMRC grant with Dr. Lim Chwee Teck (BioEng/NUS) to study biochemical

and mechanical perturbation regulating cellular mechanotransduction in 2006-2009.

6. S$1.360M Grant with Dr. Henry Yang for the Stem Cell Knowledgebase, 2006-2009

7. S$1.80M BMRC grant with Dr. Phillipa Melamad for study of frequency-dependent

differential gene expression (DBS/NUS) 2005-2008.

8. S$3.5M to plan and build a test bed for the Singapore Biomedical Grid (BMG) 2001-

2004.

9. S$3.4M to build up of expertise in Grid Computing by the InfoCom Development

Authority of Singapore 2002-2003.

10. £1.250M Hitachi Japan Ltd. to collaborate with Hitachi's Central Research Lab in

Tokyo in the project "Atomic Level Simulations of Submicron Devices" 1996-2001.

11. Three successful awards from the Joint Research Equipment Initiative (JREI) for

enhancing supercomputing hardware and technical support in the Cambridge High

Performance Computing Facility. Total of £15.5M of funding awarded

1996/1997/1998.

12. ROPA grant (£179,729) by the United Kingdom Engineering and Physical Sciences

Research Council (jointly with Dr. R J Needs and Dr. M C Payne) 1996-1999.

13. NATO Collaborative Research grant of 215,000 BF (Grant number CRG 951105jointly

with Dr. RJ Needs (Cavendish) and Prof. M-Y Chou (Georgia Tech) 1996-1998

AFFILIATIONS

American Association for Cancer Research (AACR), the American Society of Clinical Oncology (ASCO), The American Society of Human Genetics (ASHG), The New York Academy of Science (NYAS), American Association for the Advancement of Science (AAAS), American Society for Clinical Pharmacology and Therapeutics (ASCPT) and the American Medical Informatics Association (AMIA).

REFEREES

Prof. Arnold J Levine, Director, Simons Center for Systems Biology, Institute for Advanced Study, Princeton. alevine@ias.edu

Dr. William Hait, VP & Global Head of R&D, Johnson & Johnson, WHait@ITS.JNJ.COM

Prof. Robert DiPaola, Director, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, DiPaolRS@umdnj.edu

Prof. Sidney Brenner, Chairman, Biomedical Research Council, sidney_brenner@a-star.edu.sg

Prof. Sir David Lane, Executive Director, IMCB, d.p.lane@imcb.a-star.edu.sg

Prof. Robert Mair, The Master, Jesus College, Cambridge, UK, rjm50@eng.cam.ac.uk

Prof. Michael Levitt, Stanford University, Stanford, CA, michael.levitt@stanford.edu

Prof. Michael Waterman, University of Southern California, Los Angeles, msw@usc.edu

PUBLICATIONS

REVIEWS S. Vedula, C.T. Lim, T.S. Lim, G. Rajagopal, W. Hunziker, B. Lane and M. Sokabe, "Role of external mechanical forces in cell signal transduction", Biomechanics At Micro And Nanoscale Levels. H. Wada (ed), (World Scientific, Singapore, 2007).

W. M. C. Foulkes, L. Mitas, R.J. Needs and G. Rajagopal, "Quantum Monte Carlo Simulations of Solids", Reviews of Modern Physics. 73 , 33-81, (2001).

M. Nekovee, W.M.C. Foulkes, A.J. Williamson, G Rajagopal, and R.J. Needs, "A quantum Monte Carlo approach to the adiabatic connection method", 33, 189, Advances in Quantum Chemistry, Thematic volume on DFT, edited by J.M. Seminario, (1999).

W. M. C. Foulkes, R.J. Needs and G. Rajagopal, "Quantum Monte Carlo Simulations of Real Solids", High Performance Computing. R.J. Allen et. el. (eds), (Kluwer Academic Publishers, Dordrecht, 1999).

R.J. Needs, G. Rajagopal, A.J. Williamson, L.M. Fraser, S.D. Kenny, W.M.C. Foulkes, A.J. James, and P. Maccallum ``Quantum Monte Carlo studies of electronic systems '', J. Korean Physical Society 29, S116-S120 (1996).

U. Landman, R. Barnett, G. Rajagopal and A. Nitzan, ``Energetics and Dynamics of Solvation and Fission in Clusters", Proceedings of the European Physical Society, Topical Conference on Nuclear and Atomic Clusters, Finland, (1992).

R. Barnett, U. Landman, G. Rajagopal and C. Cleveland, ``Evolutionary Patterns of Structure and Stability of Clusters", NATO Advanced Research Workshop on Physics and Chemistry of Finite Systems : From Clusters to Crystals, Vol. 374, 165, edited by P. Jena, S. Khanna and B. Rao (Kluwer Academic Publishers, Dordrecht, 1992).

R. Barnett, U. Landman, G. Rajagopal and A. Nitzan, ``Dynamics, Spectra and Relaxation phenomena of excess electrons in Clusters", Israel Journal of Chemistry, 30, (1990).

Peer-reviewed Journal Articles S.P. Chia and G. Rajagopal, ``An exact calculation for the flavor-changing quark-photon vertex ", Physics Letters, 156B, 405 (1985).

G. Rajagopal, R. Barnett, A. Nitzan, U. Landman, E. Honea, P. Labistie, M.L. Homer and R.L. Whetten, ``Optical Spectra of Localized excess electrons in Alkali Halide Clusters", Physical Review Letters, 64, 2933 (1990).

R. Barnett, U. Landman, A. Nitzan and G. Rajagopal,``Born-Oppenheimer dynamics using Density-Functional Theory : Equilibrium and Fragmentation of small Sodium Clusters", Journal of Chemical Physics, 94, 608 (1991).

G. Rajagopal, R. Barnett and U. Landman, ``Metalization of Ionic Clusters ", Physical Review Letters, 67, 727, (1991).

R. Barnett, U. Landman, and G. Rajagopal,``Patterns and Barriers for fission of charged small metal Clusters", Physical Review Letters, 67, 3058, (1991).

G. Rajagopal and R.J. Needs, ``An optimized Ewald method for long-ranged potentials", Journal of Computational Physics, 115, 399 (1994).

G. Rajagopal, R.J. Needs, S. Kenny, W.M.C. Foulkes and A. James, ``Quantum Monte Carlo calculations for solids using special k-points methods", Physical Review Letters, 73 1959 (1994).

G. Rajagopal, R.J. Needs, W.M.C. Foulkes, W.M.C. Foulkes, S. Kenny and A. James, ``Variational and diffusion Quantum Monte Carlo calculations at Non-zero Wavevectors : Theory and application to Diamond-Structure Germanium", Physical Review B 51 , 10591 (1995).

S. Kenny, G. Rajagopal and R.J. Needs, ``Relativistic corrections to atomic energies using quantum Monte Carlo calculations", Physical Review A 51 , 1898 (1995).

L. Fraser, W.M.C. Foulkes, G. Rajagopal, and R.J. Needs, ``Finite-size effects and Coulomb interactions in quantum Monte Carlo calculations for homogeneous systems with periodic boundary conditions", Physical Review B 53 , 1814 (1996).

A.J. Williamson, G.Rajagopal, R.J. Needs, L. Fraser, A. James, W.M.C. Foulkes and P. Maccallum, ``Optimized Wavefunctions for quantum Monte Carlo studies of Atoms and Solids", Physical Review B 53, 9640 (1996). S.D. Kenny, G.Rajagopal, R.J. Needs, A.J. Williamson, W-K Leung, L.M. Fraser, W.M.C. Foulkes and M.J. Godfrey, ``Quantum Monte Carlo Calculations of Relativistic Corrections to the Energy of the Homogeneous Electron Gas.", Physical Review Letters, 77 1099 (1996).

A.J. Williamson, G.Rajagopal, R.J. Needs, L.M. Fraser, W.M.C. Foulkes Y. Wang and M.-Y. Chou, ``Elimination of Coulomb finite size effects in quantum many-body simulations.", Physical Review B55 R4867 (1997).

R.J. Needs and G. Rajagopal ``First-principles calculations of the adsorbate-induced surface stress of K/Al(111) ()R30". Surface Science 372, 179-184 (1997).

R.Q. Hood, M.-Y. Chou, A.J. Williamson, G.Rajagopal, R.J. Needs, W.M.C. Foulkes ``Quantum Monte Carlo Investigation of Exchange and Correlation in Silicon.", Phy. Rev. Letts. 78, 3350, 1997.

W.M.C Foulkes, M. Nekovee, R.Q. Hood, M.Y. Chou, R.J. Needs, G. Rajagopal, A.J. Williamson, "Quantum Monte Carlo studies of exchange and correlation in solids", ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 213, 125, 1997.

R.Q. Hood, M.-Y. Chou, A.J. Williamson, G. Rajagopal, and R.J. Needs, " Exchange and correlation in silicon", Physical Review B57 8972 (1998).

A.J. Williamson, R.Q. Hood, R.J. Needs, G. Rajagopal ``Diffusion Quantum Monte Carlo Calculation of the excited states of Silicon", Physical Review B57 12140 (1998).

P.R.C. Kent, R.Q. Hood, M.D. Towler, R.J. Needs and G. Rajagopal, "Quantum Monte Carlo calculations of the one-body density matrix and excitation energies of silicon", Physical Review B57 15293 (1998).

P. R. C. Kent, Randolph Q. Hood, A. J. Williamson, R. J. Needs, G. Rajagopal, and W. M. C. Foulkes, "Finite size errors in quantum many-body simulations of extended systems, Physical Review B59, 1917 (1998).

P.R.C. Kent, R.J. Needs and G. Rajagopal. "Monte Carlo energy and variance minimization techniques for optimizing many-body wave functions", Physical Review B59, 12344, (1999).

W.K. Leung, R.J. Needs, G. Rajagopal, S. Itoh and S. Ihara "Calculations of Silicon Self-Interstitials Defects", Physical Review Letters 83 , 2351, (1999). K. C. Huang, R. J. Needs, and G. Rajagopal, Comment on ``Quantum Monte Carlo study of the dipole moment of CO'' [J. Chem. Phys. 110, 11700 (1999)], J. Chem. Phys. 112, 4419, (2000).

P.R.C. Kent, M.D. Towler, R.J. Needs and G. Rajagopal, "Carbon clusters near the crossover for fullerene stability '', Physical Review B62, 15 394 (2000).

Y. Lee, P. Kent, M. Towler, R. Needs and G. Rajagopal, "Pseudopotentials for Correlated Electron Calculations ", Physical Review B62, 13347, (2000).

R. Gaudoin, M. Nekovee, W. M. C. Foulkes, R. J. Needs and G. Rajagopal, " Inhomogeneous random-phase approximation and many-electron trial wave functions ", Physical Review B63, 115115, (2001).

W.K. Leung, R.J. Needs, G. Rajagopal, S. Itoh and S. Ihara "Quantum Monte Carlo study of Silicon Self-Interstitials Defects", VLSI Design, 13(1-4): 229, (2001).

R. Gaudoin, W. M. C. Foulkes, and G. Rajagopal, " Ab Initio Calculations of the Cohesive Energy and Bulk Modulus of Aluminium”, J. Phys.: Condens. Matter 14, 8787-8793 (2002).

R.J. Needs, P.R.C. Kent, A.R. Porter, M.D. Towler and G. Rajagopal, "Quantum Monte Carlo Calculations for Ground and Excited States", Int. J. Quant. Chem. 86, 218, (2002).

Zhu H, Sun Y, Rajagopal G, Mondry A and Dhar P, “Facilitating arrhythmia simulation: the method of quantitative cellular automata ”, BioMedical Engineering OnLine 2004, 3:29 (30 August 2004).

Vedula S.R.K., Tong Seng Lim., Kausalya P.J, Gunaretnam R., Hunziker W., and Lim C.T, “Quantifying adhesion forces of tight junction proteins”, paper published in the Proceedings of the 12th Int. Conf. On Biomedical Engineering, 2005.

Vedula S.R.K., TS Lim., Kausalya P.J, Hunziker W., G. Rajagopal and Lim C.T, “Biophysical approaches for studying the integrity and function of tight junctions”, Molecular and Cellular Biomechanics, 2, 105-123, 2006.

CM Song, BH Yeo, E. Tantoso, Y. Yang, YP Lim, KB Li and G. Rajagopal, “iHAP – Integrated haplotype analysis pipeline for characterizing the haplotype structures of genes”, BMC Bioinformatics, 7:525, 2006

KH Chiam, C.M. Tan, V. Bhargava, and G. Rajagopal, “Hybrid simulations of stochastic reaction-diffusion processes for modeling intracellular signaling pathways”, Physical Review E 74, 51910, 2006.

Lee BT1, Song CM, Yeo BH, Chung CW, Chan YL, Lim TT, Chua YB, Loh MC, Ang BK, Vijayakumar P, Liew L, Lim J, Lim YP, Wong CH, Chuon D, Rajagopal G, Hill J. “Gastric Cancer(Biomarkers) Knowledgebase (GCBKB):A curated and Fully Integrated Knowledgebase of Putative Biomarkers Related to Gastric Cancer”, Biomarker Insights, 2, 1 2006.

YP Lim, TT Lim, CM Song, BH Yeoh, D. Coomber, G, Rajagopal and D. Lane, “The p53 KnowledgeBase – An Integrated Information Resource for p53 Research ”, Nature Oncogene, September 2006.

KH Chiam and G. Rajagopal, “Oscillations in Signaling Cascades”, Physical Review E 75, 061901, 2007.

BK Ang, CY Lim, SH Koh, S. Taib, KB Lim, S. Ahmad, G, Rajagopal, G. Guy and SH Ong, “ArhGAP9, a novel MAP Kinase docking protein, inhibits Erk and p38 activation through WW domain binding ”, 2:1, Journal of Molecular Signaling, 2007.

Sri Ram Krishna Vedula; Tong Seng Lim; Hui Shi; Jaya P. Kausalya; Birgitte Lane; Gunaretnam Rajagopal; Walter Hunziker “Molecular force spectroscopy of homophilic nectin-1 interactions”, Biochem Biophys Res Commun. 2007 Nov 3;362(4):886-92. Vedula, S. R.; Lim, T. S.; Kausalya, P. J.; Hunziker, W.; Rajagopal, G; Lim, C. T. Biophysical approaches for studying the integrity and function of tight junctions. Mol Cell Biomech (2005) 2:105-123. S.R.K. Vedula, T.S. Lim, P.J. Kausalya, E.B. Lane, G. Rajagopal, W. Hunziker, C.T. Lim, “Quantifying Forces Mediated by Integral Tight Junction Proteins in Cell–Cell Adhesion”, accepted for publication in Experimental Mechanics, 49:3-9, 2009. Bernett T. K. Lee, LaiLing Liew, JiaHao Lim, Jonathan K. L. Tan, Tze Chuen Lee, Pardha S. Veladandi, Yun Ping Lim, Hao Han, Gunaretnam Rajagopal, N. Leigh Anderson, “Candidate List of yoUr Biomarkers(CLUB): a Web-based Platform to Aid Cancer Biomarker Research”, Biomarker Insights, 4, 2008 Zhaohui Feng, Wenwei Hu, Gunaretnam Rajagopal and Arnold J. Levine, “The Tumor Suppressor p53: Cancer and Aging”, Cell Cycle, April, 2009. Chen, T.; Kim, S.; Zhou, J.; Metaxas, D.; Rajagopal, G; Yue, N. 3D meshless prostate segmentation and registration in image guided radiotherapy. Med Image Comput Comput Assist Interv (2009) 12:43-50.

Henry Lim, S.; Pnueli, L.; Tan, J. H.; Naor, Z.; Rajagopal, G; Melamed, P. Negative feedback governs gonadotrope frequency-decoding of gonadotropin releasing hormone pulse-frequency. PLoS One (2009) 4:e7244.

Ting Chen, Sung Kim, Sharad Goyal, Salma Jabbour, Jinghao Zhou, Gunaretnam Rajagopal, Bruce Haffty, Ning Yue, "Object-Constrained Meshless Deformable Algorithm for High Speed 3D Non-rigid Registration between CT and CBCT" , Med. Phys. 37 197 (2010). Hany Ariffin, Pierre Hainaut, Anna Puzio-Kuter, Soo Sin Choong, Adelyne Sue Li, Chan, Denis Tolkunov, Gunaretnam Rajagopal, Wenfeng Kang, Leon Li Wen Lim, Shekhar Krishnan , Kok-Siong Chen, Maria Isabel Achatz, Mawar Karsa, Jannah Shamsani, Arnold J Levine and Chang S Chan, “Whole genome sequencing analysis of phenotypic heterogeneity and anticipation in Li-Fraumeni cancer predisposition syndrome ”, PNAS, 111, 15497, 2014.