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Séminaire - Karun SinghHow do Autism spectrum disorder (ASD) risk genes impact brain development?

Abstract :

 One of the leading hypotheses is that risk genes disrupt the development of neural circuits. In the first part of my talk, I will go over our use of mouse models to study ASD risk genes and their role in synaptic development and dysfunction. In the final part, I will discuss our latest efforts to study in modeling ASD and synaptic function using gene editing of human neurons, and their potential use for drug discovery.

Selected publications

Kwan, V., Hung, C.L., White, S., Hoszapfel, N.T., Walker, S., Murtaza, N., Unda, B.K., Yuen, R.K.C., Habing, K., Milsom, C., Hope, K., Truant, R., Scherer, S.W. and Singh, K.K*. DIXDC1 phosphorylation and control of dendritic morphology is impaired by rare genetic variants. Cell Reports 17(7):1892-1904. *corresponding author. PMID: 27829159

Unda, B.K., Kwan, V. and Singh, K.K*. (2016). Neuregulin-1 regulates cortical inhibitory neuron dendrite and synapse growth through DISC1. Neural Plasticity, Article: 7694385. *corresponding author. PMID: 27847649

Lee, J.H#, Mitchell, R.R#., McNicol, J.D., Shapovalova, Z., Laronde, S., Tanasijevic, B., Milsom, C., Casado, F., Fiebig-Comyn, A., Collins, T.J., Singh, K.K., Bhatia M (2015). Single Transcription Factor Conversion of Human Blood Fate to NPCs with CNS and PNS Developmental Capacity. Cell Reports. 11(9):1367-76. #equal contributions. PMID: 26004181.

Singh, K.K., Ge, X., Mao, Y., Drane, L., Meletis, K., Samuels, B.A. and Tsai, L.H. (2010). Dixdc1 is a critical regulator of DISC1 and embryonic cortical development. Neuron 67, 33-48. PMID: 20624590.

Scientific focus :

Dr. Karun Singh is an Investigator at the Stem Cell and Cancer Research Institute (SCCRI) and an Assistant Professor with the Department of Biochemistry and Biomedical Sciences at McMaster University, Canada since 2012. He holds the David Braley Chair in Human Stem Cell Research. He obtained his PhD from the University of Toronto and his postdoctoral training at the Massachusetts Institute of Technology (MIT) in USA. Currently, Dr. Singh's independent program employs a combination of mouse and patient-derived neural cellular models to study how genes associated with Autism spectrum disorders impact brain development.

Currently his lab is focusing on 3 questions: 1. What is the normal role of ASD linked genes during mammalian brain development, with a particular emphasis on synaptic development? 2. How do ASD-linked genetic mutations impair brain (synaptic) development, from a biochemical to the functional perspective? 3. Is it possible to model neurodevelopmental disorders using human neuronal models, and use them for drug discovery?