MEDIA RELEASE Four medical doctors conducting translational and clinical research receive the Clinician Scientist Awards Four clinician scientists receive the Clinician Scientist Awards (CSAs), which provide between three and five years of research funding and salary support. They are specialists from various backgrounds including cancer, obstetrics & gynaecology and ophthalmology (see factsheet). Together with the earlier group of awardees, a total of ten CSAs are given out this year. The CSA is part of the overall talent development programme under phase II of the Singapore’s Biomedical Sciences (BMS) Initiative, co-chaired by Permanent Secretary Health, Ms Yong Ying-I and Chairman A*STAR Mr Lim Chuan Poh, to build up a pool of these personnel, supernumerary to clinical service needs. There are currently more than 80 clinician scientists working in public hospitals and national disease centres. These clinician scientists spend more than half of their time doing medical and translational research. Clinician scientists are a critical ingredient for the success of Singapore’s translational and clinical research efforts. They play a key role in developing novel, interesting research hypotheses that will one day translate into better healthcare delivery for Singapore patients. Going forward, the programme is committed to assemble a talented pipeline of clinician scientists and investigators, to support translational and clinical research. Clinician Scientist Awards recipients (December 2009) Name Institution Area of Research

Senior Investigators Dr Lee Soo Chin National University Health

System Breast Cancer

Investigators Dr Jerry Chan National University Health

System Intrauterine Gene Therapy

Dr Toh Han Chong National Cancer Centre

Nasopharyngeal cancer

Dr Louis Tong Singapore National Eye Centre

Ophthalmology

About Clinician Scientist Award

The CSA awardees will spend at least 70% of their time doing research relevant to their areas of specialty and the remaining to see patients. This enables them to stay in touch with medicine and at the same time, explore and expand new research grounds by bringing insights from their clinical work to the laboratories. The selection of the CSA awardees is based on scientific merits of their research proposals and their track records. There are two calls each year for the CSA. The award has two categories: Senior Investigator (SI) and Investigator (Inv). The former caters to senior doctors who are already actively involved in highly productive research and hold at least one peer-reviewed active research grant. They will be funded for a period of five years under the scheme. The Inv category caters to younger doctors with the potential of becoming independent investigators and who wish to develop a career in translational and clinical research. The CSA is funded by the National Research Foundation and administered by the National Medical Research Council of the MOH. Ministry of Health & A*STAR 14 December 2009

For media queries, please contact: Yeo Wen Qing Corporate Communications Ministry of Health M: +65 9642 4567 E: yeo_wen_qing@moh.gov.sg About the Biomedical Sciences Initiative The BMS Initiative was launched in June 2000 to develop BMS as a key pillar of Singapore’s economy, alongside Electronics, Engineering and Chemicals. To achieve this, the BMS Initiative is led both by a Steering Committee on Life Sciences, comprising the Ministers for Trade & Industry, Health and Education, chaired by Chairman NRF; and an Executive Committee (EXCO), chaired by the Chairman of A*STAR and the Permanent Secretary for Health. The EXCO draws on the combined experience of renowned scientists in Singapore’s BMS International Advisory Council (IAC) for strategic advice and guidance.

FACTSHEET – PROFILE OF INVESTIGATORS Clinician Scientist Awards 2009 (2) SENIOR INVESTIGATOR Dr Lee Soo Chin – CSA (SI) Senior Consultant, Department of Haematology-Oncology National University Cancer Institute, Singapore (NCIS) National University Health System Adjunct Research Fellow Cancer Science Institute of Singapore (CSI) National University of Singapore AREA OF RESEARCH: BREAST CANCER Most breast cancer patients require drug treatment, but inter-individual differences in treatment response and toxicities exist, and there are currently no reliable tests to select the best drug to individualize therapy. Development of predictive markers to guide treatment is therefore critical to improve treatment outcome, reduce unnecessary side effects, and limit health costs. In addition, there is pressing need for novel treatments to improve outcomes. The main themes of this breast cancer program are to

(1) develop biomarkers to predict response and toxicity to anti-cancer agents; (2) develop novel approaches to therapy.

The team has previously conducted and completed several breast cancer studies with serial collection of biological samples and identified gene and protein markers that distinguished responders from non-responders, and which provided insights on strategies to overcome drug resistance. The team has also completed a study evaluating the combination of a commonly used chemotherapeutic agent administered with a known metabolizing enzyme inhibitor to reduce dose requirements of the chemotherapy and demonstrated that treatment efficacy could be maintained with this strategy while reducing treatment toxicity and costs. The current proposed program builds upon this work, and will continue to design and conduct clinical trials, along with systematic collection of biological samples from patients. Three categories of clinical trials will be designed and carried out: (1) Identification of predictive biomarkers (genomics, proteomics) in advanced breast cancer patients receiving first-line pre-operative chemotherapy; (2) Studying biological changes of novel anti-cancer compounds using the window-of-opportunity studies model in early stage breast cancers prior to definitive surgery; (3) Evaluation of novel therapies in refractory, advanced breast cancers. Predictive panels of treatment response and toxicities will be developed through studies of tumor and blood genetic and protein factors. Cutting edge technologies will be applied, including genome-wide association studies that evaluate up to 1 million different human genetic variations and expression levels of up to 50,000 genes. Protein analysis will be

evaluated using a new technology that will better identify and quantify proteins. In the development of novel therapies, Dr Lee and her research team intends to distinguish their program from others internationally through development of less expensive therapies that focus on academic drug development in areas of non-commercial interest to pharmaceutical companies. The program will leverage on established basic laboratory and industry drug discovery programs, and amalgamate existing resources to evaluate these in the clinic.

INVESTIGATORS Dr Jerry Chan – CSA (INV) Assistant Professor Department of Obstetrics and Gynaecology NUS Yong Loo Lin School of Medicine Associate Consultant Department of Obstetrics and Gynaecology National University Hospital National University Health System AREA OF RESEARCH: INTRAUTERINE GENE THERAPY Monogeneic diseases are single-gene defects characterised by the absence of critical proteins. Certain conditions damage the developing fetus in utero. Some like alpha-thalassaemia major, lead to stillbirth, while others cause permanent neurological or physical disability and impaired growth, like many of the lysosomal storage diseases. Blood clotting factor deficiencies, while compatible with live-birth, are afflictions marked by life-long dependence on transfusion of the absent clotting factor. Insufficient replacement can potentiate bleeding episodes, while repeated injection of the life-saving protein is costly and often gives rise to immunological complications which in themselves can be life-threatening. Intra-uterine gene therapy (IUGT) aims to correct the genetic defect, permitting the production of the missing protein, early enough to avoid irreversible organ damage, fetal loss, and rejection of the gene-delivery vehicle by the recipient’s immune system. In well-selected cases, this therapy has the potential to rescue a fetus from an otherwise permanently debilitating, if not lethal, disease. In conditions where the affected child is normal at birth and develops symptoms during childhood, IUGT may still be a valid therapeutic option (provided prenatal diagnosis is available) as it may avert the silent onset of pathological changes and may be more effective and safer than gene therapy during childhood or adulthood. The research team is focused on developing a clinically-relevant model of IUGT for monogeneic diseases. Proof-of-concept evidence has largely resulted from rodent, canine or ovine disease models thus far. The objective is to assess the safety and effectiveness of this paradigm in a non-human primate model, which bears strong physiological and immunological resemblance to humans, by delivering a transgene with a non-pathogenic recombinant adeno-associated viral vector (rAAV), using Clotting Factor X deficiency as a disease model.

This work, in the broader context of the research group’s ongoing research in fetal gene and cellular therapy, will over the next few years generate important data relevant not only for the clinical management of congenital Factor X deficiency, but for other monogeneic diseases that will benefit from IUGT, particularly where postnatal therapeutic options are severely limited.

Dr Toh Han Chong - CSA (I) Head & Senior Consultant Medical Oncology, National Cancer Centre Singapore Visiting Consultant Changi General Hospital AREA OF RESEARCH: NASOPHARYNGEAL CANCER A current clinical trial has showed that patients will need more than chemotherapy to get more effective treatment for patients with advanced NPC to enhance responses and potentially survival rate. It will have to include other forms of therapy, either new platforms or in combination with conventional therapies. Entitled ‘Development of Epstein-Barr Virus (EBV) specific T cell therapy for Nasopharyngeal Carcinoma’, the new clinical trial to treat newly diagnosed patients with advanced NPC will examine how to leverage on the immune system or the killer T cells that it contains, to fight the NPC cells than contain EBV proteins. Apart from administering chemotherapy, patients undergoing the clinical trials will have T-cells extracted from their own blood. The T-cells will be expanded in large numbers in the lab and re-infused back into patients to fight the cancer. As a result, the T-cells are trained to specifically recognize EBV proteins on the NPC, seek them out in the cancer cells and destroy them while sparing the normal cells.

Dr Louis Tong Hak Tien –CSA (I)

Consultant and Clinician Scientist Singapore National Eye Center Assistant Director (Training and Education) & Head, Ocular Wound Healing and Therapeutics Laboratory Singapore Eye Research Institute Adjunct Associate Professor Duke-NUS Graduate Medical School Singapore AREA OF RESEARCH: MOLECULES IN PTERYGIUM - FROM CELL DYSFUNCTION TO OCULAR SURFACE PATHOLOGY Pterygium is a human ocular surface disease characterized by a proliferative, chronic inflammatory, wedge shaped lesion extending progressively from the conjunctiva onto the cornea surface. The exact mechanism and the initiating event in pterygium formation and recurrence are unknown. The prevalence of pterygium varies greatly between countries, and in some countries with higher exposure to sunlight, the prevalence can be as high as a third of the population. In Singapore, pterygium is prevalent, with pterygium

excision being the third most common ophthalmic surgical procedure after cataract surgery and corneal refractive surgery. In fact, there is no other treatment for pterygium currently apart from surgical resection, and this is still associated with an estimated 10% recurrence rate, even with current optimized techniques of surgery. Symptoms of pterygium manifest in patients in the form of redness, irritative symptoms as well as visual disturbances due to tear instability, induced astigmatism and occlusion of visual axis. Management of pterygium is a significant medical and socioeconomic burden which drains considerable healthcare resources. Dr Louis Tong’s research involves investigations into the fundamental processes that initiate inflammation and propagate this condition. If these could be understood, one could potentially use a targeted molecular approach to prevent surgical recurrence, and additionally explore the potential of a primary treatment to halt the progress of pterygium. In addition, with the use of a panel of biomarkers that are associated with pterygium recurrence, one may even be able to predict the post surgical prognosis of patients after resection. In other words, for patients predicted to have a high risk of recurrence, there may be a need to follow up more closely postoperatively and maintain a more prolonged or intensive course of post-operative anti-inflammatory eye-drops. Further to this, the cellular functions that will be evaluated in Dr Louis Tong’s study, i.e. cell adhesion, proliferation and cell migration, are extremely relevant to other disease of aberrant wound healing in the ocular surface, for example: dry eye, allergies, infections, persistent corneal epithelial defects and other such ocular surface diseases. Therefore, the molecular targets discovered in this project may further be potentially beneficial and relevant for other ocular surface diseases. Dr Tong’ s ardent hope is that the knowledge generated from his research will serve as a catalyst for the development of enhanced treatments for ocular surface diseases, with specific emphasis on pterygium.