I am an Assistant Professor at Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University. I did my PhD from Center for Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan in Molecular Biology on the “role of stem cells for the repair of aging heart”. Postdoctoral work was conducted in Dr. Mark Sussman’s lab, San Diego State University, studying the role of β-adrenergic signaling in cardiac progenitor cells and in Dr. Raj Kishore’s lab, Northwestern University, on the role of exosomes in cardiac regeneration.
please visit www.mkhanlab.com for more information.
The neonatal cardiac tissue is a proliferative organ capable of regenerating lost myocardium after injury. This regenerative window is short lived, as the cardiomyocytes differentiate terminally and exit the cell cycle. The adult heart has limited ability for cardiac regeneration with estimates for less than 1% cellular turnover throughout lifetime. The fundamental question is whether the adult cardiac tissue can be transformed to a development state enhancing cardiac repair and regeneration. We have previously shown that delivery of embryonic factors to the heart via exosomes enhances cardiac repair following myocardial infarction. We have identified miR-294 as one of the critical embryonic factors with potential beneficial effects on cardiac repair. miR-294 is an embryonic cell cycle microRNA making up 70% of the entire microRNA content in the embryonic stem cells and regulates core functions such as cell cycle, pluripotency, self-renewal and proliferation. Nevertheless, the effect of miR-294 specifically on the heart and on cardiomyocyte cell cycle has never been previously studied.
We have now documented for the first time a role for miR-294 as a driver of pro-reparative changes in the heart. These include increased cardiomyocyte cell cycle reentry and cell survival, induction of angiogenesis, restriction of infarct size and enhanced developmental molecular signaling in the heart. miR-294 represses Wee-1 kinase that dephosphorylates CDK1 releasing CDK1/Cyclin B1 complex from Wee-1 mediated inactivation, thereby promoting cell cycle reentry in cardiomyocytes (Figure). Our delivery strategy employed a Tet-regulated AAV9-based approach for the miRNA induction in the heart for 14 days following myocardial injury. The duration goes beyond any study for miRNA delivery to the heart to date. Follow-up of mice for up to 8 weeks after miR-294 administration showed enhanced cardiac function together with increased cardiomyocyte replenishment after myocardial infarction injury.