Randolph L. Geary, MD, FACS
Randolph L. Geary, M.D., FACS, Professor of Surgery - Vascular Surgery, Professor of Pathology - Comparative Medicine
Dr. Geary was recruited to Wake Forest from the University of Washington, Seattle, where he completed medical school, general surgery residency and a vascular surgery fellowship. While in Seattle, Dr. Geary worked in the laboratory of mentor Alexander W. Clowes, M.D., exploring regulation of vascular smooth muscle cell growth by blood flow and shear stress and the potential for viral vectors to achieve vascular gene transfer. He was then recruited to Wake Forest, where he continues to pursue his interests in vascular surgery and vascular biology as director of the Vascular Biology Laboratory in the Division of Surgical Sciences. He is currently Professor of Vascular and Endovascular Surgery with cross-appointments in Departments of Pathology-Comparative Medicine, and the Wake Forest Institute for Regenerative Medicine.
SYNOPSIS OF AREA OF INTEREST: Arterial injury and repair, constrictive artery wall remodeling, restenosis and blood vessel bioengineering.
DETAILED AREA OF INTEREST: Virtually all forms of arterial reconstruction result in mechanical injury to the artery wall, which stimulates a cascade of injury responses as the vessel heals. In many patients the injury response is excessive, leading to recurrent narrowing of the artery at the site of repair. This is termed "restenosis." Restenosis is an enormous public heath issue as millions of arterial revascularization procedures are performed each year and about one third will fail from restenosis within 2 years (e.g., following angioplasty, stenting, endarterectomy, or arterial bypass). Restenosis has two basic underlying structural explanations - new tissue formation within the lumen of the vessel and inward constriction or shrinkage of the artery wall surrounding sites of injury. New tissue forms from growth of smooth muscle cells in response to cytokines and growth factors released at sites of injury and then subsequent deposition of extracellular matrix. This new tissue, termed neointima, then encroaches upon the lumen causing restenosis. As the artery wall heals it also will often shrink as cells and extra-cellular matrix reorganize into a smaller geometry. This "constrictive remodeling" is in many ways analogous to wound contraction and fibrosis and also contributes to lumen encroachment. While much is known about the regulation of smooth muscle cell hyperplasia, much less is known about the molecular regulation of artery wall constrictive remodeling. Our lab is studying the effects of various matrix components on tissue contraction. Specifically, we are studying the interaction between cells, collagen, and hyaluronic acid - a prominent component of the matrix secreted by smooth muscle cells as they repair the injured artery wall- at sites of artery wall reconstruction. It is unclear whether hyaluronan improves or impairs reorganization of collagen following injury. To address this question we are studying the artery wall response to injury in mice that have altered receptor profiles for hyaluronan and responses of these cells during remodeling of collagen in tissue culture. The overarching goal is to identify molecular targets to block constrictive remodeling after arterial reconstruction as a means of preventing restenosis. Our lab is also collaborating with WFIRM on characterizing the in vivo responses of bioengineered blood vessels. Many parallels are likely in the healing of bioengineered arteries and the injury response in native arteries. By manipulating cells and scaffoldings used in constructing bioengineered blood vessels, we may be able to alter healing responses to improve vessel maturation.