The Department of Physiology welcomes Dr. Bhairab Singh, PhD
Assistant Professor, Department of Pediatrics. Dr. Bhairab Singh is a Research Scientist for the department of Biomedical Engineering at the University of Minnesota. His Seminar is titled ” Molecular Regulation of Mammalian Heart Regeneration” The adult human heart has limited potential to regenerate. Previously, we showed the conserved GLI1/MYCN cascade in heart regeneration from newt to human. Further, networks involved in the proliferation-maturation transition of the human cardiomyocytes are lacking, hence, limiting the development of regenerative therapies. We have identified the Hh-GLI2-CKS1B cascade, as a regulator of the transition between proliferation and maturation in hiPSC-CMs. Gene Concept Network (GCN) analysis revealed enrichment of oxygen-rich metabolic cascade with reduced proliferation in early-to-late-stage hiPSC-CMs and in neonatal to adult mouse CM. Relative to early-stage CM, GLI-members are downregulated in late-stage CM. Inhibition of Hh- or GLI-proteins in early-stage CM decreased proliferation and enhanced CM maturation. Further, we showed GLI2 binds the promoter region and regulates CKS1B expression in hiPSC-CMs. Overexpression of CKS1B in late-stage hiPSC-CMs using modified mRNA increased proliferation; surprisingly, under the same conditions maturation features were reduced. These data establish the GLI2-CKS1B network as a toggle between proliferation and maturation in CM and as a . Analysis of the ischemic (HF) and dilated-cardiomyopathy (DCM) patients, we observed significant and exclusive enrichment of GLI2-factor relative to the non-failing heart. These findings advance our mechanistic understanding of regenerative medicine for human heart disease.
Please send an email to Miranda Smith(firstname.lastname@example.org) if you are interested in the seminar.