Neurodegenerative diseases are increasingly recognized as one of the leading causes of disability and death worldwide; however, no cure is available for these diseases. Insufficient understanding of the mechanisms underlying neurodegenerative diseases hinders the development of effective treatment strategies. The key questions that remain enigmatic in the neurodegenerative research field are (1) how do neurons die? (2) why certain neurons are selectively affected? and (3) does inflammatory response protect neurons from dying or accelerate the dying process? Elucidation of the neurodegenerative process, the discovery of the vulnerable neuronal cell types and identification of the role of inflammation in the nervous system would facilitate the development of powerful and effective strategies for therapeutic intervention.
Our lab explores amyotrophic lateral sclerosis (ALS) to answer these questions with the aim of identifying targetable pathways for therapeutic interventions. We recently created a new ALS mouse model, MATR3 S85C knock-in mouse, which recapitulates early-stage features of human ALS including motor deficits, Purkinje cell degeneration, motor neuron defects and neuroinflammation. With this clinically relevant disease model, we will employ genetics, molecular and cell biology, RNA profiling and high-throughput genetic screens to (1) identify the early disease events in the neurodegenerative process, (2) elucidate the mechanism underlying selective neuronal vulnerability and (3) determine the role of microglia in ALS pathogenesis during early-stage ALS. Addressing these questions will advance our understanding of the disease mechanism and enable the development of early intervention strategies for ALS.
- MMG3006Y Future Directions in Medical Genomics
- Genetics and Genome Biology Program, SickKids Research Institute