SEMINAR: Pharmacologic Inhibition of HDAC1 Enhances the Reparative Capacity of Human Cardiac Mesenchymal Stromal Cells in a Chronic Model of Heart Failure

Dr. Joseph Moore IV
When Nov 02, 2017
from 12:00 PM to 01:30 PM
Where Shumaker Bldg, Room 139
Contact Name
Contact Phone 852-7485
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Abstract:  Previously we identified HDAC1 as a modulator of human cardiac mesenchymal stromal cell (CMC) lineage specification. There, CMCs depleted of HDAC1 exhibited induction of a core cardiogenic program and a heightened aptitude to acquire a cardiomyogenic/vasculogenic cell-like fate in vitro. We postulated that a pharmacologic inhibitor of HDAC1 activity in human CMCs would recapitulate the effects of genetic depletion of this protein in human CMCs and improve their cardiac reparative capacity in the setting of myocardial infarction (MI) in vivo. Human CMCs treated with the benzamide HDAC1 inhibitor, entinostat (MS-275), and transplanted in a chronic MI model exhibited a dose- and timedependent induction of a cardiogenic transcriptional program relative to untreated CMCs in vitro.  In preliminary in vivo studies, entinostat-treated CMCs exhibited superior ability to attenuate adverse LV remodeling and yielded greater improvement in ventricular function relative to untreated CMCs. These results suggest that HDAC1 inhibition enhances the therapeutic potency of CMCs, possibly by augmenting CMC cardiogenic lineage-commitment.


Speaker:  Dr. Joseph Moore IV obtained his Ph.D. in Biochemistry and Molecular Biology at the University of Louisville before completing a postdoctoral fellowship in Pediatric Oncology at Johns Hopkins University. Dr. Moore’s laboratory focuses on the use of biochemical and developmental programming strategies to investigate the genetic and molecular mechanisms modulating the survival and cardiac reparative properties of adult cardiac progenitor populations (CPCs) residing in the adult mammalian heart. The long term goal of such work is to identify molecular pathways that could be exploited, through genetic modification or pharmacological pretreatment, to enhance the therapeutic efficacy of various autologous cardiac progenitor populations in patients with ischemic cardiac injury.