Govindaswamy Chinnadurai, PhD

Professor of Molecular Microbiology and Immunology, Saint Louis University

The transcriptional corepressor CTBP1 in neurodevelopment Read More

Email: g.chinnadurai@health.slu.edu
Lab Phone: (314) 977-8785
Website: Faculty webpage
Lab Location: Doisy Research Center 647 (1100 South Grand Blvd)

The transcriptional corepressor CTBP1 in neurodevelopment

CTBP1 is a transcriptional corepressor discovered in our laboratory.  CTBP family proteins (CTBP1 and 2) control important developmental functions in vertebrates.  The nuclear splice forms (Long) of CTBPs transcriptionally repress target genes by recruiting various chromatin modifying factors and DNA-binding repressors to the promoter regions of chromatin.  CtBP1 has been shown to be important for the synaptic activities of neurons.  The genomes of certain patients with neurodevelopmental defects such as ataxia, hypotonia, intellectual disability, and tooth root/enamel defects contain a specific recurrent de novo mutation in CTBP1 (W331 of CTBP1-Short isoform/W342 of CTBP1-Long isoform).  This mutation maps within CTBP1 sequences involved in forming the primary protein-protein interaction cleft that is required for interaction with cofactors of the CTBP1-corepressor complex.  Altered transcriptional activities of the pathogenic CTBP1 mutant allele may contribute to neurodevelopmental defects in children.  We are modeling CTBP1-mutated developmental phenotypes in neuronal cell models differentiated from patient-derived iPSC.  The patient-derived cell models are used to determine the transcriptional profiles, associated mechanisms of regulation, and morphological/electrophysiological phenotypes of neurons differentiated from patient and normal stem cells.  The disease ontogeny and phenotypes are also investigated using an engineered knock-in mutant mouse model.  Thus, our studies will provide novel insights into the role of CTBP1 in neuronal development and the mechanisms contributing to the pathological outcome in patients expressing the mutant allele.

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