Vascular Biology Institute and Molecular and Cellular Pharmacology Receive $2M Grant

The Miller School’s Vascular Biology Institute and Department of Molecular and Cellular Pharmacology have been awarded a $2 million grant from the National Heart, Lung and Blood Institute, part of the National Institutes of Health. The grant will support a translational research program that combines gene therapy with engineered stem cells for the treatment of cardiovascular disease.

Keith A. Webster, Ph.D., FAHA, the Walter G. Ross Distinguished Chair in Vascular Biology, professor of molecular and cellular pharmacology, director of the Vascular Biology Institute and principal investigator on the grant, received the award notice this month.

“This unique program uses UM-proprietary technology involving a new regulatory gene switch called “conditional silencing” to deliver hypoxia-regulated angiogenic factors to cardiac and skeletal muscles in adeno-associated viral (AAV) vectors,” said Dr. Webster. “These funds will steer the program from basic pre-clinical studies to clinical trials.”

Dr. Webster explained that the gene switch allows, for the first time, safe and effective delivery of these growth factors to ischemic muscle. “Because expression is long term but tightly regulated by ischemia, it promotes arteriogenesis as well as angiogenesis, and the therapy is safe because gene expression is extinguished as soon as the tissue is reperfused, thereby eliminating potentially harmful angiogenic stimuli from normal tissues.”

This research puts the Miller School at the forefront of the field by combining optimized stem cell therapy with safe and effective gene therapy for the treatment of ischemic cardiovascular disease, the leading cause of death in the western world.

Webster’s group recently reported regeneration, with no adverse side effects, of the entire femoral artery in a mouse model of critical limb ischemia using these techniques. The team includes Jeffrey Boden, Ph.D. student; Jennipher Adi, Ph.D., post-doctoral associate; Jian Qin Wei, M.D., research assistant professor; Nikhil Adi, assistant research scientist; Liliana Cesar, D.V.M., senior research associate; Huijun Yuan, Ph.D., assistant research scientist; Huilan Wang, Ph.D., post-doctoral associate; and Lina Shehadeh, Ph.D., assistant professor of medicine.

They are in the process of filing an Investigational New Drug application with the FDA, and clinical trials are planned in the United States within the next two years.

The project also involves collaborations with Si Pham, M.D., professor of surgery and director of cardiopulmonary transplantation; Ian McNiece, Ph.D., professor of medicine and director of experimental and clinical therapies at the Interdisciplinary Stem Cell Institute; Eduardo de Marchena, M.D., associate dean for international medicine and professor of medicine; and David Grant, surgical recovery manager.

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