The Neurotherapeutics lab is broadly interested in using human induced pluripotent stem cells to model neurodegeneration, and using this as a platform for therapeutic discovery.

Amyotrophic Lateral Sclerosis (ALS)

ALS or Lou Gehrig's Disease is a progressive neurodegenerative disease affecting motor neurons in the brain and spinal cord. Approximately 90% of ALS cases are sporadic where the cause of disease is not known and the remaining are familial forms of ALS. Familial ALS means the disease is inherited. 

To date, a number of genetic mutations have been associated with the disease, such as SOD1, FUS, TDP-43, HNRNPA1, C9ORF72 and so on.

 

To study ALS, we have engineered known ALS mutations into otherwise healthy lines using CRISPR/Cas9 technology. By doing so, we can better investigate disease pathogenesis and progression. Apart from differentiating these isogenic pairs of iPSCs towards motor neurons, we also derive spinal astrocytes from these cell lines and are investigating the contributions of astrocytes towards disease.

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The long term goal of the laboratory is to model the disease using iPSCs from patients with a known ALS-causing mutation, and to extend our understanding of disease progression in familial cases to sporadic ALS so as to better diagnose, and treat ALS in future.

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Frontotemporal Dementia (FTD)

FTD refers to a group of disorders causing progressive neuronal loss in the brain's frontal lobes and/or temporal lobes, the areas generally associated with language, behavior and personality. Signs and symptoms vary depending on the area of the brain affected. Some people with FTD undergo dramatic changes in their personality and become socially inappropriate, impulsive or emotionally indifferent, while others lose the ability to use language.

FTD is often misdiagnosed as psychiatric disease or Alzheimer's disease, which greatly hampers the treatment of FTD. The laboratory is especially interested in using the mutant TDP43 and C9ORF72 expansion models to understand the pathogenesis of FTD and using this as a platform to identify new therapeutic targets for prevention of FTD.

 

 

Astrocyte Biology

Astrocytes are the most abundant cell type in the central nervous system, and support normal neuronal health and function by providing metabolic support, modulating synaptic transmission, and their involvement in uptake and release of factors. There is strong evidence for astrocyte (non-cell autonomous) toxicity in many neurodegenerative diseases including ALS. Our goal is to be able to decipher the molecular basis of astrocyte toxicity.