Karun Singh

Open to recruiting graduate students (MSc and PhD)

Dr Singh completed his undergraduate studies at McMaster University, and his Ph.D. studies at the University of Toronto and the Hospital for Sick Children.

He then performed postdoctoral studies at the Massachusetts Institute of Technology (MIT). He joined McMaster University from 2012-2020 where he was a Scientist and the Neural Program Lead at the Stem Cell and Cancer Research Institute, and an Associate Professor in the Department of Biochemistry and Biomedical Sciences at McMaster University.

Dr Singh joined the Krembil Research Institute at UHN in 2020 as a Senior Scientist, and is a member of the Donald K. Johnson Eye Institute.

He holds appointments in the Departments of Ophthalmology and Vision Sciences, and Laboratory Medicine and Pathobiology (LMP) at the University of Toronto.

He holds funding from CIHR, NSERC and the Ontario Brain Institute.

Research Synopsis

The Singh Lab

Located in the Krembil Research Institute (UHN), the space consists of both wet lab bench space and newly renovated tissue culture facilities.

Lab personnel and trainees will have access to biological safety cabinets, incubators to perform cell line, primary cell culture and human induced pluripotent stem cell work.

In addition, electrophysiological techniques (patch clamp and multielectrode arrays) are newly purchased, and trainees have access to:

• animal facilities (onsite)
• animal behavioral facilities
• crogenic storage
• core microscope
• PCR
• flow cytometry facilities.

The Singh lab will provide guidance to graduate students, including:

• teaching of equipment usage
• help with project management
• analysis of data
• presentation and writing skills.

Our research

Our research program studies developmental and adult brain disorders.

We use genetically engineered mouse models and patient stem cell-derived neural cells (2D and 3D organoids) as our model systems.

We identify pathogenic mechanisms that contribute to neurological disorders with next generation sequencing, proteomics, electrophysiology and imaging.

Our ultimate goal is to use this information to identify or develop novel therapeutics that reverse clinical conditions.

Currently our lab has 2 major areas of focus:

1. Neurodevelopmental Disorders

Our lab has a strong interest in studying the genetic causes of Autism spectrum disorders and neuropsychiatric conditions.

We have identified novel signaling pathways contributing to genetic risk factors including TAOK2, the 15q13.3 deletion and 16p11.2 deletion syndromes.

We are also working on newly identified candidate risk genes using mouse and human iPSC models.

2. Neurodegenerative and Vision Disorders

We are initiating new collaborative research projects on neurodegenerative conditions (eg. Alzheimer’s and Parkinson’s disease) and vision disorders.

We are using our human iPS cell platform to develop new 2D and 3D brain organoid models from different cohorts of patients, to study disease mechanisms using multiple technological approaches.

Selected Publications

Deneault, E., Faheem, M., White, S.H., Rodrigues, D.C., Sun, S., Wei, W., Piekna, A., Thompson, T., Howe, J.L., Kwan, V., Walker, S., Pasceri, P., Roth, F.P., Yuen, R.K.C., Singh, K.K., Ellis, J. and Scherer, S.W. (2018). Autistic Patient-SpecificCNTN5-/+or EHMT2-/+iPSC-Derived Neurons Develop Hyperactive Neuronal Networks. eLIFE doi: 10.7554/eLife.40092. 

Deneault, E., White, S.H., Rodrigues, D.C., Ross, P.J., Faheem, M., Zaslavsky, K., Wang, Z., Alexandrova, R., Pellecchia, G., Wei, W., Piekna, A., Kaur, G., Howe, J.L., Kwan, V., Thiruvahindrapuram, B., Walker, S., Lionel, A.C., Pasceri, P., Merico, D., Yuen, R.K.C., Singh, K.K., Ellis, J., Scherer, S.W. (2018) Disruption of Autism Spectrum Disorder-Susceptibility Genes Predominantly Reduces Functional Connectivity of Isogenic Human Neurons. Stem Cell Reports. 11 (5), P1211-1225. 

Uddin, M., Unda, B.K., Kwan, V., Holzapfel, N.T., White, S.H., Chalil, L., Woodbury-Smith, M., Ho, K.S., Harward, E., Murtaza, N., Dave, B., Pellecchia, G., D’Abate, L., Nalpathamkalam, T., Lamoureux, S., Wei, J., Speevak, M., Stavropoulos, J., Hope, K.J., Doble, B.W., Nielson, J., Wasserman, E.R., Scherer, S.W. and Singh, K.K. (2018) OTUD7A regulates to neurodevelopmental phenotypes in the 15q13.3 microdeletion syndrome. American Journal of Human Genetics (Cell Press).  102, p278-295.

Richter, M., Murtaza, N., White, S, Walker, S., Scharrenberg, R., Morellini, F., Naumann, A., Schwanke, B., Kwan, V., Yuen, R., Scherer, S.W., Singh, K.K. and de Anda, F.C. (2018) Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling. Molecular Psychiatry February 21, 2018. (Nature Publishing Group). 

Kwan, V., Hung, C.L., White, S., Hozapfel, 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. (2016). DIXDC1 phosphorylation and control of dendritic morphology is impaired by rare genetic variants. Cell Reports 17(7):1892-1904. PMID: 27829159.

Appointments

Senior Scientist, Krembil Research Institute (Krembil)

Associate Professor, Department of Ophthalmology & Vision Sciences, University of Toronto