Assistant Professor of Pharmacology
AHFMR Scholar, Canada Research Chair, Tier II

Research Interests: Neurobiology of Huntington's disease

Huntington's disease (HD) is an inherited neurodegenerative disorder that causes progressive motor and cognitive dysfunction. The disease is caused by the expansion of a polyglutamine  (polyQ) stretch in a protein named huntingtin. The most affected areas of the brain are corpus striatum and cortex, which explains the loss of motor control and the cognitive and psychiatric symptoms in HD patients.

The exact mechanism by which neurodegeneration occurs in HD is poorly understood. Neurons in HD brains are profoundly affected at multiple levels, from gene transcription to vesicle trafficking, cell signaling, energy metabolism and mitochondrial and synaptic function. It is not clear how mutant huntingtin affects so many aspects of the cell physiology. Most likely mutant huntingtin triggers a cascade of events or domino effect, where more and more cell functions  become progressively impaired until the neurons die.

Our research is directed toward the understanding of the molecular mechanisms underlying HD. Previous work by us and our collaborators has shown that one of the early dysfunctions triggered by mutant huntingtin is aberrant metabolism of specific lipids such as cholesterol and gangliosides. These lipids are important components of membrane microdomains known as lipid rafts that serve as hubs for cell signaling and that are crucial to the function of the nervous system, to synaptic transmission
and cell-cell communication. Projects in our laboratory are mainly focused on understanding the effects of brain lipid dysregulation on function and survival of HD neurons, and on identifying the underlying mechanisms and potential therapeutic treatments.
For our research we use transgenic animal and cell models of HD, as well as cell lines derived from HD patients. Our experimental approach is multidisciplinary, involving biochemical, molecular and cell biology techniques.