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Doctoral Student Receives Grant through the American Heart Association

Third-year graduate student Sunil Yadav had never met Pamela Knous before their first handshake at the Rosenstiel Medical Science Building recently, but thanks to a shared medical interest, the Naples woman will play a significant role in the advancement of the doctoral student’s career.

From left, Pamela Knous, Ralph Sacco, M.D., Danuta Szczesna-Cordary, Ph.D., Sunil Yadav, graduate student Yoel H. Sitbon, and Arnold Schmidt.

Knous, along with her husband, Arnold Schmidt, and representatives of the American Heart Association (AHA), came to the University of Miami Leonard M. Miller School of Medicine on June 20 to present Yadav with a check that will fund his research grant aimed at developing an innovative treatment for heart disease.

“I couldn’t be more excited,” said Yadav, 25, who works in the laboratory of Danuta Szczesna-Cordary, Ph.D., professor of molecular and cellular pharmacology. “Basic science research is so important; it forms the basis for clinical interventions. Grants like this make it all possible.”

Last year, Yadav submitted a project to the AHA called “The effect of pseudo-phosphorylation of myosin RLC on the improvement of cardiac function in hypertrophic cardiomyopathy.”

The project received high marks, so the AHA, which frequently partners with private foundations and individual donors to share support for projects of excellent scientific merit, reached out to Knous, a former member of the AHA’s National Board who had expressed an interest in supporting research on heart disease and genetic cardiomyopathies.

“I am proud to have been affiliated with the AHA since 2007,” said Knous. “It is a tremendous organization  dedicated to achieving its mission of building healthier lives free of cardiovascular disease and stroke.”

Yadav, who is originally from Nepal, is focused on finding a targeted treatment for hypertrophic cardiomyopathy (HCM), a common form of heart disease in which a portion of the heart muscle, or myocardium, thickens, making it harder for the heart to pump blood.

Yadav is hopeful his research will one day lead to clinical trials, and potentially, lifesaving treatment for cardiomyopathy. Currently, physicians only treat the disease symptomatically.

“It doesn’t target the major culprit, mostly genetic mutations in one of several sarcomeric genes that encode for proteins of the contractile apparatus of the heart,” said Yadav, who emphasizes an urgent need for novel therapy to prevent and/or reverse the structural and functional defects of the failing heart. “My research is focused on mutations in a specific molecule, myosin regulatory light chain (RLC) which has been implicated in a malignant form of HCM. Our targeted gene therapy approach is aimed at mimicking RLC phosphorylation, a physiological phenomenon critical for normal cardiac contractility, and one that is often depressed in most malignant cardiomyopathies.”

Pamela Knous and Sunil Yadav in the lab.

The work Yadav is doing is an extension of a project Dr. Szczesna-Cordary, the principal investigator on the project, initiated in 2005 after receiving her fourth AHA grant-in-aid to study familial HCM in animal models expressing HCM-linked mutations in the human ventricular myosin RLC.

Her research interests concentrate on understanding the mechanisms underlying myosin light chain-induced cardiomyopathies and explore target-specific therapeutic approaches. In addition to HCM, the lab is also studying pathophysiology of dilated (DCM) and restrictive (RCM) cardiomyopathy caused by genetic mutations in myosin regulatory and essential light chains.

Her lab has generated and characterized multiple transgenic mouse models of cardiomyopathies and used them to study the fundamental morphological and functional indices that are impaired by disease-causing mutations. Rigorous experiments, coupled with sophisticated instrumentation, allow her lab to carry out comprehensive sets of experiments, from analyzing the function of the intact heart in vivo (by echocardiography, invasive hemodynamics), and assessing muscle fiber mechanics (force development and myofilament calcium sensitivity) to simultaneously deriving structural information on papillary muscle fibers by small angle X-ray diffraction. They have been able to analyze proteomic/phosphoproteomic parameters and signal transduction pathways in these mouse models of HCM, DCM and RCM with a longstanding goal to provide mechanistic insights into the structural, functional and single myosin molecule determinants of heart remodeling.

Dr. Szczesna-Cordary says the grant is a strong motivational tool for young scientists facing an increasingly competitive fundraising field.

“These fellowships are absolutely critical for the graduate students and post-doctoral fellows to continue work in the laboratory and discover new approaches to battle heart disease using preclinical mouse models of HCM, DCM, and RCM,” she said. “They help our students to advance their career and graduate studies and help them convince themselves of the validity of what they are doing.”

Yadav gave a short presentation on his research to Knous, Schmidt, and AHA representatives Monica Seif, Jennifer Campbell, and Amanda Palumbo.

Afterward, he led them on a tour of the laboratory.

“Research like this is so important,” said Knous. “Sunil is looking for new and novel ways to fight heart disease.”

Knous and Schmidt first learned about research being done at UM during a 2014 tour highlighting what the AHA’s support has meant to the University. They also support a separate AHA project at UCLA.

Knous worked with Ralph L. Sacco, M.D., M.S., professor and Olemberg Chair of Neurology at the Miller School, while serving on the board of the American Heart Association. Sacco was the AHA national president from 2010-2011, the first neurologist to hold the position.

The University of Miami Miller School of Medicine and the American Heart Association are longstanding partners in the fight to save lives. Thanks to the American Heart Association’s incredible generosity for more than four decades, the University of Miami has received over $45 million dedicated to heart disease research, in areas such as cardiology, neurology, stem cell therapy, pharmacology, cell biology and many others.

In addition, UM cardiologist, Robert J. Myerburg, M.D., professor of medicine and physiology, holds the American Heart Association Chair in Cardiovascular Research.

The American Heart Association’s mission is to build healthier lives, free of cardiovascular diseases and stroke – America’s No. 1 and No. 5 killers. The AHA works with millions of volunteers to fund innovative research, fight for stronger public health policies, and provide lifesaving tools and information to prevent and treat these diseases.

“This research grant, through the AHA,  provides us with the opportunity to fund Sunil’s early career research activities as well as allows us to support the heart health of the communities that are meaningful to us,” said Knous.


Tags: American Heart Association, Danuta Szczesna-Cordary, hypertrophic cardiomyopathy, Ralph Sacco