2013 Wylie Scholar
Assistant Professor of Surgery
University of Maryland
The Wylie Grant was awarded to support Dr. Monahan’s research identifying the mechanisms responsible for vein graft, angioplasty, and stent failure. Dr. Monahan studies the body’s reaction to surgery known as intimal hyperplasia.
As a vascular surgeon, Dr. Monahan performs both bypass surgery and angioplasty (inflation of a balloon within a diseased segment of artery) to relieve arterial blockages. Over seven million cardiovascular bypass operations and angioplasty procedures are performed in the U.S. each year. Bypass grafting, endarterectomy, and angioplasty remain plagued by restenosis, or recurrent narrowing of the affected vessel, which affects up to 30-40% of procedures within six months. Restenosis or intimal hyperplasia represents a large clinical problem.
A normal blood vessel is a three-layer structure consisting of the intima, media, and adventitia. The intima is populated with endothelial cells. In the setting of trauma – including surgical bypass, angioplasty, or stenting – the normally quiescent, contractile medial smooth muscle cells dedifferentiate. These cells revert to a more primitive migratory, proliferative, and secretory form. These cells migrate to the intima and cause the lesion observed in intimal hyperplasia. Intimal hyperplasia reduces vessel diameter and ultimately limits the patency of all cardiovascular reconstructions. Dr. Monahan is presently focusing on methods of specifically inhibiting vascular smooth muscle cell migration and proliferation. Present treatments for the prevention of intimal hyperplasia are limited because they inhibit both smooth muscle and endothelial cell migration and proliferation. Inhibition of endothelial re-growth mandates that patients take blood thinners for an indefinite period of time.
Dr. Monahan has identified a protein, MARCKS, that when knocked down, inhibits smooth muscle cell migration and proliferation with no effect on endothelial cells. He is presently exploring the mechanism of the differential effect of MARCKS signaling in these two cell types. This protein is potentially a powerful target for the prevention of intimal hyperplasia. The work that Dr. Monahan is doing with support from the Wylie Scholarship represents the important first steps in the development of a therapy to prevent the formation of intimal hyperplasia.
Dr. Monahan is presently on the faculty at the University of Maryland School of Medicine where he is performing his research. He is mentored by a former Wylie Scholar, Dr. Rajabrata Sarkar.
“Support from the Wylie Scholarship has allowed me the freedom to pursue MARCKS as a potential target for therapy to prevent intimal hyperplasia. This support is especially valuable in the very competitive present funding environment. This funding will allow me to generate data and transition to an independently funded surgeon-scientist.”