Koh Tong Wey

Impact

Parkinson’s disease and aging Parkinson’s disease (PD) is a debilitating neurological movement disorder, best known for motor symptoms like tremor and rigidity. Except in rare familial forms of the disease, PD tends to affect older individuals, and the disease progresses with age. Late stage patients may also suffer from dementia.

Typically, PD is diagnosed by subjective observation and managed with symptom-suppressing drugs. Upon emergence of motor symptoms, 30% of neurons in the motor centre, substantia nigra, are irreversibly lost.

Thought to stay undetected for decades, Tong-Wey’s lab wants to bring hope to PD patients and their families. Heterogeneity of PD suggests complex interactions between genes, environment and the aging process. The team is working to address three unmet needs – objective early diagnosis tools, neuroprotective drugs and preventive measures.

Collaborations, Achievements & Honours

  • Recipient, Healthy Longevity Catalyst Award, US National Academy of Medicine (2020 – 2022)
  • Recipient, Healthy Brain Ageing Grant, Singapore (2019 – 2022)
  • Recipient, National Research Foundation Fellowship Grant, Singapore (2015 – 2021)
  • Recipient, Best Talk Award, Cold Spring Harbour Asia Conference, Invertebrate Neurobiology (2012)
  • Recipient, Best Graduate Student’s Publication, Baylor College of Medicine (2004)
  • Collaboration on novel diagnostics with National Neuroscience Institute, Singapore and global start-ups Entopsis and Pathnova
  • Collaboration on neuroprotective genes study with the Human Brain Tissue Resource Centre, China
  • Collaboration on anti-ageing measures study with the NUHS Centre for Healthy Ageing, Singapore
  • Identified ferric chloride chemistry as a promising tool that will differentially label Parkinson’s disease-enriched urine metabolites
  • Identified 12 neuroprotective genes that suppress the action of SNCA, a key disease agent of Parkinson’s disease
  • Identified neuroinflammation as a modifiable target for anti-ageing intervention measures

Research Areas

Developmental Biology, Neurodegenerative Disease, Genetics & Genomics

Affiliations

  • Principal Investigator, TLL
  • Assistant Professor, Department of Biological Sciences, NUS

Question

How can complex interactions between genes, the environment and an aging process prevent neurodegenerative diseases?

Approach

Current diagnosis methods for PD rely on behavioural symptoms, which manifest after most movement-controlling dopaminergic neurons have died. There is no cure for the disease. Symptomatic treatment require individualized regimes on a trial-and-error basis. These challenges arise from the lack of understanding of the underlying mechanisms in PD.

As such, Tong-Wey’s lab is studying SNCA, a key gene underlying PD. It encodes the alpha-synuclein protein, which are found in aggregates, called Lewy Bodies, in post-mortem brains. It is hypothesized that diverse genetic and cellular interactions between SNCA and different genes may partly explain the heterogeneity of PD symptoms. These interactions are currently studied to reveal PD-like phenotypes in aging.

Short-living model organisms are used in Tong-Wey’s lab. The fruit fly (Drosophila melanogaster) and African turquoise killifish (Nothobranchius furzeri) live to a maximum lifespan of three and six months respectively. Using organisms with short lifespans, iterative testing of hypotheses or ideas for reproducibility and refinement of mechanistic understanding are executed in a robust manner.

By performing a genetic screen in the fruit fly, genetic interactors of alpha-synuclein were identified and studied using multiple approaches, including optical imaging of dopaminergic neuron activity, electron microscopy and electrophysiology.

Further investigations on killifish brains also uncovered synuclein-immunoreactive punctate structures in aging brains. Notably, no genetic modification was needed to induce these punctate structures.

The lab is currently working towards an early diagnosis tool, neuroprotective drug and preventive measures for PD. Investigations in the aging killifish nervous system are likely to yield insights into a natural progression of synuclein-related pathology during aging.

In addition, Tong-Wey’s team is collaborating with start-ups to develop urine-based tool for early diagnosis of PD using colorimetric chemistry and computational pattern recognition.

Having identified 12 neuroprotective genes relevant to PD, Tong-Wey is also targeting the importance of the age process in the etiology of PD, testing dietary modifications and drugs to delay brain ageing.

Bio

Tong-Wey earned his bachelor’s and master’s degrees in molecular biology from the National University of Singapore (NUS), and a Ph.D. in Developmental Biology and Embryology at Baylor College of Medicine in the lab of Hugo Bellen. He joined TLL in 2014, after completing his post-doctoral training with John Carlson at Yale University.

Tong-Wey’s extensive background in life sciences research began during a summer training at Tata Institute of Fundamental Research in India, where he was introduced to the neurobiology of the Drosophila fruit fly.

Subsequently, he conducted a large forward genetic screen in Drosophila for mutants with defective neurotransmission, and discovered how specific leg sensory neurons arouse Drosophila male sexual behaviour through sensing female pheromones. Tong-Wey also developed an interest in a link between Type 2 Diabetes (T2D) and neurodegeneration, which has grown into his research programme today.

Adjunct Principal Investigator

Koh Tong Wey

The lab studies how complex gene interactions cause brain degeneration in Parkinson’s disease.

Contact

tongwey@tll.org.sg
+65 6872 7820
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