1. Copyright © 2011 National University Health System Education Clinical Care Research How Health Sciences Would Love To Work With Computer Science! John E.L. Wong, MBBS, FAMS, FRCP, FACP Isabel Chan Professor of Medical Sciences Vice Provost (Academic Medicine), National University of Singapore Deputy Chief Executive, National University Health System Director, National University Cancer Institute, Singapore NUS SoC Faculty Retreat 13 September 2013, 12-1pm, Rasa Shangri La, Sentosa

2. Copyright © 2011 National University Health System 2. Divider Introducing new topic NUHS: Academic Medicine in Singapore

3. National University Health System NUS Yong Loo Lin School of Medicine NUS Faculty of Dentistry Saw Swee Hock School of Public Health Alice Lee Center for Nursing Studies National University Hospital Governing Board Chief Executive (Lead) Deputy Chief Executive

4. Copyright © 2011 National University Health System National University Health System, Singapore

5. 2. Divider Introducing new topic NUHS Research Strategy

6. 6 diseases interrogated by 8 platforms in a matrix fashion NUHS Research Strategy

7. 2. Divider Introducing new topic Key Disease Research Areas Cancer Cardiovascular Metabolic Medicine Infectious Diseases Neuroscience Eye Diseases

8. Research Themes 1.Early Phase Drug Development 2.Developmental Therapeutics in Endemic Cancers 3.Immunotherapy in Cancer 4.Childhood Malignancies 5.Translating Epithelial-Mesenchymal Transition for Cancer Prognostics and Therapeutics Cancer National University Cancer Institute, Singapore Research Directors: Phillip Koeffler, Soo-Chin Lee Development of Novel Therapeutics and Biomarker-Directed Strategies in Refractory Solid Tumors and Haematological Malignancies Phillip KOEFFLER Soo-Chin LEE

9. Cancer Cancer Science Institute, Singapore Present: 17 PIs and 200 scientific staff At steady state: up to 25 PIs and approx 350 staff & students Daniel TENEN GOH Boon Cher CHNG Wee Joo Phillip KOEFFLER LEE Soo- Chin Basic programs – experimental models Translational programs – human studies Cancers Affecting Singaporeans Gastric Lung Liver Leukemia Nasopharyngeal Cancer Biology Experimental Therapeutics Genomic Oncology Breast Cancer Stem Cells Personalised Medicine for Asian population Finding Cancers Early to Enable Cure IMPACT:

10. Gastric Cancer Note: Data for Univ Cambridge retrieved on 3 July 13 (27 May for all others).

11. To understand the biological processes leading to cardiovascular disease Target parts of those disease pathways with new treatments in order to prevent or ameliorate the disease Heart Failure –new candidate biomarkers for diagnosis and prognosis –Establishing specific improved therapies for subtypes of heart failure. Cardiac Valve Disease –Assess value of plasma biomarker measurements in predicting progression of valve disease –and in optimising timing of interventions such as valve replacement or repair. Acute Coronary Syndrome –Exploration of novel candidate peptide biomarker tests for detection of cardiac ischaemia or heart failure Ventricular Repair –Pre-clinical studies devoted to the development of bioengineered tissue constructs seeded with progenitor cells to be used in the repair of post- infarction left ventricular scar. Cardiovascular Epigenomics and Epigenetics Mark RICHARDS TAN Huay Cheem Roger FOO Carolyn LAM Mark CHAN Cardiovascular Diseases

12. Singapore Heart Failure Outcomes and Phenotypes (SHOP) study: SG Heart Failure (HF) cases average 8 yrs younger than in NZ Diabetes in SG HF cases > NZ (55% versus 27%) Diabetes may be a more important underlying substrate for HF in SG than in western populations IMPACT: 1.Development of new clinical practice guidelines for heart failure and coronary artery disease in Asian patients 2.Improve the ability to predict the onset of HF, anticipate what kind of HF will occur and the course of its progression 3.New treatment approaches to HF National University Heart Centre Spore (NUHCS) Cardiovascular Research Institute (CVRI) Mark RICHARDS TAN Huay Cheem Cardiovascular Diseases Roger FOO Carolyn LAM Mark CHAN

13. Note: Data for Univ Cambridge retrieved on 3 July 13 (27 May for all others). Cardiovascular Diseases

14. Diabetes, Obesity and Metabolism Address the rising incidence of metabolic diseases in Singapore, where diabetes now affects 11.3% of Singaporeans (nearly 7% rise within 2 decades) Asian features of the metabolic diseases – Singapore comprises 3 major Ethnic differences in the prevalence rates and pathogenesis of metabolic diseases We have: –built up capacity for epidemiology, physiology and metabolic imaging to facilitate target identification and validation –established in-vitro models for all three ethnic groups We have active programs: Our Research Focus 14 2. Nutrient metabolism and insulin resistance Role of protein intake, amino acid metabolism & fat intake/metabolism in pathogenesis of insulin resistance Role of carbohydrate quality on glycemic control & appetite regulation Role of altered nutrient handling in the ability of bariatric surgery to ameliorate diabetes 3. Burden of diabetes mellitus & novel models of health care delivery for chronic disease Unique features of type 2 diabetes in Asia and designing of stratified medicine Designing of programs for prevention of type 2 diabetes mellitus Efficacy of patient-centered medical home in reducing hospitalization and improving outcomes 1. Pathogenesis of type 2 diabetes Mechanistic basis in genetic variants with unique effects in populations of Asian ancestry Ethnic differences in insulin resistance CHONG Yap Seng TAI E Shyong LEE Yung Seng Sue-Anne TOH

15. Implications for Clinical Practice Higher incidence of gestational diabetes (GDM) than previously suspected & higher glucose levels in mothers - even in the absence of GDM – can still affect infant adiposity. Obesity has a major role to play in the risk of diabetes in Chinese and Malays. However, Indians are at high risk of diabetes, but obesity has a smaller impact. IMPACT: Interventions to reduce obesity and diabetes in the population How to advise public on healthier food choices & lifestyles Initial Findings Life Course Cohort: Human Metabolic Studies:

16. Note: Data for Univ Cambridge retrieved on 3 July 13 (27 May for all others). Metabolic Disease

17. Provide innovative solutions to local, regional and global infectious disease challenges through a world-leading research programme Extensive collaborations across NUS, A*STAR Research Institutes and Industry Partners. We have active programs: 1.Antibiotic Resistance Surveillance/Infection Control Methicillin-resistant Staphylococcus aureus (MRSA), multi-resistant gram- negative bacilli, hand hygiene and device-associated infections 2.Influenza Influenza pathogenesis, pandemic influenza preparedness and business continuity, guidance to health policies, cost-effective prevention strategies, mathematical modeling of influenza infections, novel prophylactic and therapeutic approaches 3.HIV HIV pathogenesis and its metabolic consequences (dyslipidemia, heart diseases, osteoporosis, diabetes mellitus and other metabolic dysfunctions), improvement of HIV treatment strategies and patient management 4.Tuberculosis Pathogenesis, genotyping and phenotyping of the various strains, clinical and immunological characterization, development of diagnostic tests and assays, development of cost-effective treatment strategies 5.Dengue Naoki YAMAMOTO Vincent CHOW Paul TAMBYAH Dale FISHER Nick PATON Paul MACARY Infectious Diseases

19. Current Neuroscience research programmes at YLLSoM focused on ischaemic stroke, dementia, and neurodegeneration: 1.Ischaemic stroke focus on intracranial stenosis or intracranial large artery disease, which is the redominant stroke subtype among Asians Aim: to understand better the mechanism of stroke, improve diagnostic and prognostic methods, improve patient care and treatment, develop new treatment modality including studying the feasibility of stem cell therapy 2.Vascular and Neurodegenerative Mechanisms in Dementia Aim: to identify biomarkers for vascular and neurodegenerative mechanisms, and obtain insights into the mechanisms of interaction may lead to potential therapeutic approaches, through study of clinical and epidemiological cohorts, neuroimaging, neurochemical and animal studies 3.Neurodegeneration focusing on role of excitotoxicity & free radicals in aging and dementia, role of glial cells and vascular factors in promoting neuroinflammation, role of metal ions and lipids in neurodegeneration, exploring neuroprotection and promoting resolution of neuronal injury Aim: to conduct in-depth analyses of factors which contribute to, or modulate, degeneration of the nervous system Neuroscience Christopher CHEN Carlos IBANEZ Peter WONG Barry HALLIWELL SOONG Tuck Wah

20. Dementia and Age-related Cognitive Impairment Singapore ageing population: by 2030, 19% of the population will be aged 60 & above. Dementia is a disease most common in the elderly Singapore and Asia face an epidemic of dementia and cognitive impairment in the next few decades Neuroscience Christopher CHEN Prevalence of intracranial stenosis (ICS) 40-50% in Chinese stroke patients 8-10% in Caucasian Stroke patients Association of ICS with cognitive impairment NCI- Non cognitive impairment CIND- Cognitive Impairment, No Dementia Impact of Intracranial Stenosis Carlos IBANEZ Peter WONG Barry HALLIWELL SOONG Tuck Wah AIM : Development of new screening and treatment strategies for dementia and cognitive impairment

21. Eye Disease There is an epidemic of myopia in Singapore SAW Seang Mei WONG Tien Yin Singapore Eye Research Institute Glaucoma Research Retina Research Oculoplastics Research Cataract Research Cornea Research Neuro-Opthalmology Research Singapore* published the most papers per capita (*95% of papers SERI/NUS) Donald TAN AUNG Tin

22. Copyright © 2011 National University Health System 2. Divider Introducing new topic Core Facilities

23. Clinical Imaging Research Centre Center for Translational Research & Diagnostics Investigational Medicine Unit Clinical Nutrition Research Centre Medical Engineering Research & Commercialization Initiative Core Facilities

24. Investigational Medicine Unit (IMU) Services: 1.Providing clinical research support 2.Providing administrative support 3.Training in clinical trial management 4.Storage of trial drugs and biological samples Facilities: –Clinical Biostatistics and Pharmacometric Unit –Cardiovascular Imaging Core Laboratory –Pharmacokinetic/Pharmacodynamic Analytical Laboratory –Genomics Core Laboratory –Clinical Pharmacology Group Website: http://www.imu.com.sg/ GOH Boon Cher

25. Clinical Imaging Research Centre (CIRC) Partnership between NUS and A*STAR dedicated to developing advanced imaging in humans Facilities: 3T MRI, the combined positron emission tomography and magnetic resonance imaging (PET-MR) system and a PET/CT, complemented by a radiochemistry suite and cyclotron that will enable in-house production of a range of clinically relevant PET tracers. David TOWNSEND Website: http://www.circ.nus.edu.sg/

26. Siemens TIM TRIO 3T MR scanner Imaging Facilities at CIRC Siemens mMR PET/MR scanner Siemens mCT PET/CT scanner Siemens PRISMA 3T MR scanner

27. 2013

28. Centre for Translational Research and Diagnostics (CTRAD) DMOC Biospecimen Repository >800,000 biospecimens Logistics infrastructure Clinical Data, Cohort Samples Translational Research >$5M high-end technology >150 publications >$5M in industry grants Molecular Diagnostics CAP accreditation >100 assays >19,000 reports/year Accredited molecular pathology capabilities Disease Programs Clinician Scientists Clinical Trials Research Cores NUHIndustry Stratified Medicine MDC Richie SOONG Website: http://www.csi.nus.edu.sg/

29. Medical Engineering Research and Commercialization Initiative (M.E.R.C.I.) Aims to spearhead the development of medical devices by leveraging the strengths of NUHS and NUS faculty in the engineering and physical sciences. 4 themes: Microsensors Diabetes Cardiovascular Minimally Invasive Surgery Website: http://medicine.nus.edu.sg/medsur/contactUs_staffDirectory.html Rachel HONG Melvin LOH

30. Overview of projects 30 MICROSENSORS Biosensors for vascular graft Tactile steerable catheter Ultrasonic needle End organ perfusion sensor (PPG) CARDIOVASCULAR AAA Stent Preferential covered stent for embolic prevention Percutaneous Mitral valve Biodegradable caval valve MINIMALLY INVASIVE Navigation tool for Colonoscopy Vascular access monitoring using Bioimpedence Magnetic field based NG tube tracking Gastroduodenal chute Endoscopic raman spectrometry OPHTHAMOLOGY Glaucoma drainage device Multi focal Contact lens TELEMEDICINE Wireless body area networks (Fujitsu) SPECIAL PROJECTS Sub $300 Ultrasound Graphene for Med Dev Two Spin-offs Next Projects: Healthcare Automation

31. Joint initiative between the Singapore Institute for Clinical Sciences, A*STAR and the National University Health System. First to commission the first whole body calorimeter in Asia, aiming to conduct nutrition research with sophisticated instruments. Specializes in basic and translational human nutrition research involving studies across the life cycle. Clinical Nutrition Research Centre (CNRC) Jeyakumar HENRY Website: http://www.nutritionresearch.edu.sg/

32. Copyright © 2011 National University Health System 2. Divider Introducing new topic Some of the challenges we need help in

33. How to predict patients at high risk of complications / early relapse / recurrent admissions How to run hospitals more “e-fficiently” (E-Health) How to improve the co-ordination of patient care between the specialties How to look for potential drug side effects (Pharmacovigilance) Wish List - Hospital

34. Identifying actionable genetic mutations; how to store and curate genetic information we currently do not understand (Genomic Medicine) How to improve imaging (Medical Imaging and Analysis) How to model and simulate epidemics Wish List - Schools

35. NUHS: Shaping Medicine for the Future