Alexander W. Clowes, M.D.

Department of Surgery
Center of Vascular Biology
University of Washington

From left to right: (back row) Shinsuke Kikuchi, Richard Kenagy, Andrew Burzo, Tony Grieff, Kevin Xiong, Lihua Chen; (front row) Julieann Marshall, Alexander Clowes, Lu Gao

Primary Research:
Over the last 30 years, we have been interested in how intimal hyperplasia and stenosis/restenosis develop and the factors that determine outcome, particularly in vascular grafts. While we have previously focused our research on the mechanisms controlling intimal thickening and atrophy in baboon GORE-TEX grafts, we have recently begun to define in humans the underlying factors that account for vein graft failure. In the course of this transition, we have worked with other vascular colleagues to design and conduct the PREVENT III trial. Although the trial did not succeed in that the drug tested, an E2F decoy, was ineffective in preventing vein graft failure, nevertheless it did demonstrate in 1400 patients that 25-30% of grafts fail during the first year after surgery largely on account of intimal hyperplasia and pathological remodeling. Our laboratory, in collaboration with Dr. Michael Sobel at the University of Washington and more recently with Dr. Michael Conte at the University of California – San Francisco, has taken a vascular biological and genetic approach and has shown during the last 2 years that there may be a genetic basis for vein graft failure. The research is funded by the NHLBI.

Lab Members:

Richard Kenagy, PhD, Research Scientist, Lab Manager
Lihua Chen, PhD, Research Scientist
Shinsuke Kikuchi, MD, Visiting Research Scholar
Lu Gao, MD, PhD, Postdoctoral Fellow
Julieann Marshall, Clinical Research Coordinator
Anthony Grieff, BA, Society for Vascular Surgery Student Research Fellow
Andrew Burzo, Undergraduate

Number of trainees in the laboratory: 4

Recent Publications:

1. Conte MS, Owens CD, Belkin M, Creager MA, Edwards KL, Gasper WJ, Kenagy RD, LeBoeuf RC, Sobel M, Clowes A. A single nucleotide polymorphism in the p27(Kip1) gene is associated with primary patency of lower extremity vein bypass grafts. J Vasc Surg 57(5):1179-85, 2013.

2. Moreno K, Murray-Wijelath J, Yagi M, Kohler T, Hatsukami T, Clowes A, Sobel M.: Circulating inflammatory cells are associated with vein graft stenosis. J Vasc Surg 54(4):1124-30, 2011.

3. Kenagy RD, Min S-K, Mulvihill E, Clowes AW. A link between smooth muscle cell death and extracellular matrix degradation during vascular atrophy. J Vasc Surg 54:182-91, 2011

Collaborative Relationships:

University of Washington:
Michael Sobel, M.D., Dept of Surgery
Jonathan Himmelfarb, M.D., Director, Kidney Research Institute

University of California, San Francisco:
Michael Conte, M.D.

University of California, Los Angeles:
A. Jake Lusis, Ph.D.