UT Southwestern physician-scientist Hesham Sadek, M.D., Ph.D., has received the prestigious National Institutes of Health (NIH) Outstanding Investigator Award to support his ongoing research into mechanisms behind heart regeneration that could lead to treatments for heart failure.
There are currently no therapies that can reverse heart failure or induce heart regeneration in humans. This award will accelerate the development of therapeutics that can reactivate the cardiomyocyte cell cycle and induce heart regeneration in humans."
Dr. Hesham Sadek, M.D., Ph.D., Professor of Internal Medicine, Biophysics, and Molecular Biology, Associate Director of the Hamon Center for Regenerative Science and Medicine at UTSW
The award promotes productivity and innovation by scientists whose outstanding record of research demonstrates their ability to make major contributions to heart research. It provides investigators like Dr. Sadek increased freedom to conduct research that breaks new ground and allow them to take greater risks and pursue research that requires a longer time frame.
"I am honored by this recognition of our contributions and NIH's confidence in our ability to develop a highly ambitious cardiac regeneration research program," Dr. Sadek said.
The competitive grant totals $7.5 million over seven years. Dr. Sadek said funds will be used to identify molecular mechanisms through which cardiac work and oxygenation regulate the heart's ability to regenerate.
About 6.2 million adults in the U.S. suffer from heart failure, a disorder caused by viruses, toxins, high blood pressure, or heart attacks in which the heart struggles to pump enough blood to meet the body's demands. Current treatments for heart failure, including ACE inhibitors and beta blockers, center on trying to stop a vicious cycle of heart muscle loss as strain further damages remaining muscle, causing more heart cells to die.
In 2011, Dr. Sadek, along with longtime collaborator Eric Olson, Ph.D., Director of the Hamon Center for Regenerative Science and Medicine and Chair of Molecular Biology, and their colleagues, showed that mouse hearts damaged in the first few days of life can regenerate, spurred by the division of cardiomyocytes, the cells responsible for a heart's contractile force. However, this capacity is lost by seven days of age, an abrupt turning point in which division of these cells slows dramatically and the cells enlarge.
Since then, Dr. Sadek and colleagues have identified several key molecular pathways that mediate the loss of this regenerative capacity, including those triggered by increased cardiac load and oxygenation shortly after birth. By manipulating these pathways, the Sadek lab has been able to reactivate heart regeneration, even in adult mice. It has also shown that mechanical heart pumps called left ventricular assist devices (LVADs), commonly used to treat heart failure, can reactivate the cardiomyocyte cell cycle in the adult human heart.
"As a basic scientist and practicing cardiologist, Dr. Sadek has brought a unique perspective to our understanding of the molecular basis of cardiac disease," Dr. Olson said. "His discoveries of regenerative mechanisms that are active in the newborn heart and silenced in adulthood have provided new strategies for repair of the injured heart."
Dr. Sadek holds the J. Fred Schoellkopf Jr. Chair in Cardiology. Dr. Olson holds the Pogue Distinguished Chair in Research on Cardiac Birth Defects; The Robert A. Welch Distinguished Chair in Science; and the Annie and Willie Nelson Professorship in Stem Cell Research.
The relationship between calcium consumption at various times of the day and cardiovascular disease