Download Annex Aopens in a new window - National Medical Research Council

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-ofopportunity 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 alphathalassaemia 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.