My major research and clinical interests are the neurochemistry, molecular biology and treatment of stroke and dementia.

Behavioural and psychiatric disorders in dementia : In collaboration with colleagues from Oxford, London, UCLA, SGH and NUS, we have been investigating the neurochemistry of patients with Alzheimer's Disease and other related disorders. By correlating these with prospectively studied clinical features and genetic markers we aim to identify novel therapeutic targets.

Prognostic factors and Cognitive consequences of Stroke : In collaboration with NUS and GIS, we have been studying biochemical and genetic markers underlying the pathophysiology of stroke. Longitudinal studies are also in progress to study the natural history, risk factors for and treatment to prevent cognitive impairment and dementia after stroke. We aim to discover new therapeutic approaches.

Clinical Trials  I have developed an international reputation for the organisation and execution of academically driven as well as industry sponsored trials. My current focus is on developing a regional network for innovative trials into conditions prevalent and pertinent to Asia. I also plan to enhance Singapore's capability for conducting increasingly sophisticated early phase studies utilising biomarkers such as neuroimaging.

Overall, my aim is to develop synergies with basic neuroscience research : to translate novel scientific findings into therapeutic possibilities as well as to provide clinical insights for disease specific laboratory research. 

Future plans
In the next 5 years, I intend to develop upon the theme of "Translational Research and Clinical Trials in Stroke and Dementia" so as to lead a productive and integrated research programme.

The aim would be to deepen existing collaborations and to develop new ones so that we can benefit Neuroscience research in Singapore and provide a basis for the training of young clinicians / scientists keen on pursuing and developing a research career.

Dementia

Neurochemistry Our work has shown that alterations in receptor density as well as common genetic variation in a variety of neurochemical systems have an influence on the development of a number of de novo symptoms of BPSD in AD.

We aim to continue investigation of the neurochemical and genetic basis of BPSD with an emphasis on the second messenger systems involved. The correlation of particular neurochemical parameters to clinical symptoms provides a basis for further studies into rational treatment with drugs and in vivo screening for patients at risk of developing behavioral symptoms.

Our research may also have applications for the treatment of the cognitive symptoms of dementia. 

Neuroimaging  We plan to perform longitudinal imaging and neuropsychological studies of post-stroke patients with cognitive impairment. Arterial Spin Labelling (ASL) MRI techniques developed in Singapore will  be utilized to investigate the relationship between perfusion and cognitive function in dementia, particularly in patients with intracranial atherosclerosis and with a view to use in clinical trials. We also intend to utilize advanced MRI techniques to investigate pathophysiology and effects of treatment in transgenic mice models of Alzheimer's Disease.

Genetics Our future plans are to collaborate with GIS on further genome wide screens for new vascular cognitive impairment and BPSD genes.

Neuroscience We have well established links with other neuroscientists in Singapore and overseas and our aim would be to deepen & broaden our collaborations. A novel and potentially vital development is a deepening relationship with the newly formed Glaxo Smith Kline Neurodegenerative Diseases group at Biopolis.

Stroke

Neurochemistry We aim to identify novel biomarkers for stroke suitable for diagnostic or prognostic purposes as well as continuing with the very promising area of cysteine and hydrogen sulphide neurotoxicity so as to identify new therapeutic targets.

Neuroimaging In collaboration with the Department of Diagnostic Radiology, SGH we utilize multimodal magnetic imaging to study the efficacy of nitric oxide and the effect of blood pressure in stroke. We shall be using other modalities such as diffusion tensor imaging, in line with our long term strategy of using bioimaging as an outcome measure and to understand pathophysiology.

Other Biomarkers  We are investigating the association of retinal microvascular signs in acute stroke with stroke subtype & prognosis and to further investigate other markers such as central compliance, the Ankle-Brachial Index and Intracranial Stenosis in Stroke patients with regards risk of recurrent vascular events.

Genetics  In addition to our ongoing work with the GIS on haplotype-based case control association analysis of homocysteine metabolism candidate genes, we plan to extend this work to other candidate genes, young stroke patients  intracranial disease and cognitive impairment.

Clinical Trials

A major goal is to developing a regional Neuroscience clinical trials network with a coordinating centre based in Singapore for larger scale trials as well as sophisticated Phase II studies utilising biomarkers such as neuroimaging, neurochemistry and molecular biology.

Singapore is already a regional center for neuroscience clinical trial organization and leadership. The first regionally designed acute stroke trial was organized between the NNI, Chinese University of Hong Kong and CTERU in 2001 leading to a recent publication of our collaboration in Lancet Neurology. A further regional acute stroke trial utilizing advanced surrogate outcomes (multiple emboli detection & diffusion weighted imaging) is already in progress and the NMRC has just approved funding for a novel regional stroke trial. By investing in, restructuring, and increasing the capacity of our neuroscience clinical trials program, we would enable Singapore to take a leading role in clinical trials and thus further the development of the biomedical sciences by improving the visibility of Singapore and the region's neuroscience capabilities to pharmaceutical / biomedical enterprises; coordinating existing clinical trial centres, and development of new centres of excellence; more efficiently convert recent scientific discoveries into effective interventions and increase patient access to clinical trials.

Several objectives and plans are listed below :

1. Address compelling clinical questions confronting Neuroscientists and their patients in Asia.
2. Increase the pace of development and clinical testing for new therapeutic and preventive agents.
3. Coordinating the development and maximizing the use of existing clinical trials infrastructure to study prevention and treatment outcomes and other clinically relevant questions.
4. Coordinating the development and maximizing the use of existing clinical trials infrastructure to study prevention and treatment outcomes and other clinically relevant questions.
5. Create collaborations to optimize resources.
6. Identify relevant biomarkers.

As part of the above strategy, we organized the 1^st Asia-Pacific Stroke Workshop at Biopolis in September 2005. It was a highly successful meeting which brought together stroke clinicians and scientists from the region to plan a regional research agenda for stroke. Several key conditions (intracranial stenosis, haemorrhage) have been identified as targets for clinical trials and research. We intend to develop in the first instance a stroke research network and for a regional stroke trials center to be based in Singapore with the support of the CTERU.

A similar programme is planned for dementia and I have taken the lead in forming a Dementia Consortium in Singapore which may be the basis of a flagship programme for the future.