PUBLIC RELEASE DATE:

22-May-2014

Contact: Jeremy Walter Jeremy.Walter@tuhs.temple.edu 215-707-7882 Temple University Health System

(Philadelphia, PA) Innovative treatments for heart failure are lacking, leaving the nearly six million Americans who suffer from the condition with little hope for a cure. But thanks to an $11.5-million Program Project Grant (PPG) from the National Heart, Lung, and Blood Institute (NHLBI), scientists at Temple University School of Medicine are now set to further their investigation of key molecular mechanisms in heart failure, an effort that is expected to lead to the development of new heart therapies.

The Principal Investigator on the new PPG award is Dr. Walter J. Koch, PhD, The William Wikoff Smith Chair in Cardiovascular Medicine, Professor and Chair of the Department of Pharmacology, and Director of the Center for Translational Medicine at Temple University School of Medicine (TUSM). Dr. Koch is working alongside two other Temple researchers on the Program Project Grant Dr. Steven R. Houser, PhD, FAHA, Senior Associate Dean for Research, Professor and Chair of the Department of Physiology, and Director of the Cardiovascular Research Center at TUSM; and Dr. Arthur M. Feldman, MD, PhD, Executive Dean of TUSM, and Chief Academic Officer of Temple University Health System.

Each of the scientists is leading a specific project for the grant, with all three projects being natural outgrowths of ongoing research in their individual laboratories. The three projects focus on signaling pathways implicated in cardiac injury and repair, and they likely intersect in heart failure pathology, underscoring the significance of the collaborative research effort.

"The Program Project Grant give us the opportunity to develop novel approaches to treat ischemic heart disease," explained Dr. Houser. "Our goal will be to have new therapeutics ready for patients through our PPG."

The new award represents the second round of PPG funding for the three researchers. Over the course of their previous funding cycle, Drs. Feldman, Houser, and Koch developed highly integrated research programs aimed at better understanding the signaling molecules involved in heart failure. Their preliminary research resulted in the identification of the three signaling pathways that the researchers are now investigating for the second PPG. Those pathways center on an enzyme known as G-protein coupled receptor kinase 5 (GRK5) and on molecules known as arginine vasopressin (AVP) type 1A receptors and transient receptor potential (TRP) channels.

GRK5 forms the basis of Dr. Koch's portion of the PPG. In earlier work, he and colleagues found that the enzyme, which normally resides in the cytoplasm of heart cells, can be transported into the heart cell nucleus. There, in the cockpit of the cell, GRK5 takes control over the activity of certain genes. Its manipulations ultimately cause heart cells to increase in size, creating a condition known as hypertrophy, which is a central feature of heart failure.

Dr. Feldman's PPG research explores the role of AVP type 1A receptors in cardiac injury. In previous work in mice, Feldman's team found that the density of AVP receptors increases in the heart following cardiac injury. The change in receptor expression was associated with diminished heart function. In the next steps of investigation, Feldman hopes to elucidate the mechanism underlying that association.

Read this article:

Temple scientists receive $11.5 million grant for heart failure research