Scientific Advisory Board Member

Karun K. Singh, Ph.D. Senior Scientist, Krembil Research Institute, University Health Network (UHN) Associate Professor

Dr. Karun Singh’s research has made significant impact on our knowledge of signaling mechanisms that regulate brain development, and of the genetic risk factors underlying neurodevelopmental disorders. Neurological disorders of the developing brain such as autism impacts 1 in 66 individuals in Canada while schizophrenia affects 1% of the population. Affected individuals and families are burdened by life-long health, social and economic issues. Unfortunately, there are no specific therapies for individuals because these disorders remain poorly understood. However, since neurodevelopmental disorders have a strong genetic basis, this provides a starting point to identify underlying disease pathogenesis mechanisms. Dr. Singh’s work combines powerful human genetic studies and animal models. Using this approach, he has made novel insights into how autism and schizophrenia risk genes disrupt neural development. For example, in complex brain disorders where there is a loss of multiple genes (named microdeletions), Dr. Singh’s team recently identified that in each disorder, a single gene plays a strong role in the development of the disease. In addition, his work has uncovered that patient-derived mutations in multiple genes disrupt synaptic communication between neurons in the brain. These discoveries have pinpointed precise signaling pathways that are disrupted by mutations in high risk genes, providing a path forward for screening and identifying therapeutics that will reverse the neural impairments. Building on these discoveries, Dr. Singh has established clinical and genetic sequencing collaborators to create a resource of human induced pluripotent stem cell (iPS cell) models to study brain development disorders. He is combining this approach with CRISPR gene editing to better dissect the precise mechanisms by which genetic mutations cause defects in neural development. His platform has established a mechanism to identify drugs that will be streamlined for future clinical trials.