KOH Tong-Wey, Ph.D, Principal Investigator

Dr. Koh received his Bachelor’s and Master’s degrees from National University of Singapore. During a summer training at Tata Institute of Fundamental Research in India, he was introduced to the neurobiology of the fruitfly, Drosophila. Subsequently, for his Ph.D. training at Baylor College of Medicine, he conducted a large forward genetic screen in Drosophila for mutants with defective neurotransmission in the lab of Hugo Bellen. He then moved to Yale for his post-doctoral training with John Carlson’s lab, where he discovered how specific leg sensory neurons arouse Drosophila male sexual behavior through sensing female pheromones. Also at Yale, he developed an interest in a link between Type 2 diabetes (T2D) and neurodegeneration, which has grown into his research program as he joined TLL in Sep 2014.

You may wish to contact Dr KOH Tong-Wey at:

Tel: (65) 6872 7554, (65) 6872 7820 (DID) Email: tongwey@tll.org.sg

For information on PhD studies at TLL, click HERE

 

Figure 1. Diabetes increases the risk of neurodegenerative diseases, like dementia/Alzheimer’s disease and Parkinson’s disease.

Background and significance

Patient care for neurodegenerative diseases impose great costs on societies; the combined societal cost of neurodegenerative conditions like dementia, Alzheimer’s disease and Parkinson’s disease in Singapore was SGD1.4 billion in 2009 (a third of the healthcare budget). As T2D patients are predisposed to neurodegeneration, and as both T2D and neurodegeneration are increasingly prevalent, costs will escalate.

We have produced novel evidence that a T2D-like condition predisposes flies toward neurodegeneration, thus suggesting that the interaction between the two diseases is conserved between flies and humans. This evolutionary conservation provides an exciting opportunity to harness the vast repository of genetic tools in Drosophila to tackle this important human health issue.

Research focus

  1. Investigate the effect of insulin signaling on the degenerating brain
  2. Identify genetic variations that predispose insulin-resistant organisms to neurodegeneration

1. Insulin signaling and neurodegeneration

A hallmark of T2D is the failure of tissues to respond to insulin. Underlining a link between T2D and neurodegeneration, recent clinical trials on dementia patients involving brain-directed delivery of insulin showed promising preliminary results. To elucidate the effect of insulin on the brains of dementia patients, we will investigate the effect of insulin signaling in degenerating nervous systems in flies. Our long term objective is to help design improved versions of insulin-based therapy for neurodegenerative diseases.

2. Mutations that predispose insulin-resistant organisms to neurodegeneration

Genetic variations among T2D patients will likely influence their likelihood of developing neurodegenerative diseases. It is important to identify the critical genetic variations. Currently, we are conducting unbiased genetic screens in flies to identify mutations that interact with an insulin-resistant state to cause neurodegeneration; this will allow the identification of corresponding human genetic variations. Our long term objective is to help identify diabetes patients who are predisposed to neurodegenerative diseases.

Figure 2. Fly brains (left) share many conserved gene functions with human brains (right). Therefore, identifying fly mutant genes that cause neurodegeneration will allow us find corresponding human genes.