Journal Club -Transient Introduction of miR-294 in the Heart Promotes Cardiomyocyte Cell Cycle Reentry After Injury

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My name is Mohsin Khan and I am an Assistant Professor at Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University. I did my PhD from Lahore, Pakistan in Molecular Biology on the “role of stem cells for the repair of aging heart”. I joined Dr Mark Sussman’s lab for a postdoctoral fellowship on studying the role of β-adrenergic signaling in cardiac progenitor cells. I continued my career afterwards and joined Dr Raj Kishore’s lab as a research scientist to work on exosomes and cardiac regeneration.

As an independent principal investigator, the goal of research in my lab is to develop novel strategies for cardiac regeneration in the heart after pathological injury. The neonatal cardiac tissue is a proliferative organ capable of regenerating lost myocardium after injury. This regenerative window however, 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 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. Nevertheless, the effect of miR-294 specifically on the heart and in particular on cardiomyoycte cell cycle has never been previously studied.

In this study, we have documented for the first time a novel role for miR-294 as a driver of pro-reparative changes in the heart that include increased cardiomyocyte cell cycle reentry, increased cell survival, induction of angiogenesis, restriction of infarct size and enhanced developmental molecular signaling in the heart that collectively augments cardiac function after myocardial infarction.

Our findings highlight a role for miR-294 in the heart in the context of cardiac regeneration. Our delivery strategy employed a tet-regulated AAV9-based approach for the miR induction in the heart for 14 days following myocardial injury that goes beyond any reported approach for miRNA delivery to the heart to date.

Outside of science, I play, watch live soccer and can make any kind of conversation related to soccer. In my free time, love to travel, hike and kayak. I have a young family and with my spouse an academic PI, life is wonderfully hectic!

 

References

Borden A, Kurian J, Nickoloff E, Yang Y, Troupes C, Ibetti J, Lucchese AM, Gao E, Mohsin S, Koch WJ, Houser SR, Koshore R, Khan M. Transient introduction of miR-294 in the heart promotes cardiomyocyte cell cycle reentry after injury. Circ Res. 2019; published ahead of print.

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