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William Guilford

William Guilford

Associate Professor of Biomedical Engineering

Undergraduate Program Director

B. S., Saint Francis College, 1986
Ph.D., Physiology, University of Arizona, 1993

Box 800759
University of Virginia
Charlottesville, VA 22908

whg2n@virginia.edu

Curriculum vitae

Selected Publications

Research Interests

In the Molecular Biomechanics Laboratory, our goal is to understand the molecular mechanisms by which cells move, with particular emphasis on muscle contraction, and how this relates to cardiovascular disease. We examine the mechanics of these processes at the level of individual molecules using techniques including the in vitro motility assay and laser trap transducer. The in vitro motility assay is a means by which the mechanics of the individual proteins that cause muscle contraction, actin and myosin, can be studied in isolation from other cell components. A laser trap is, quite literally, a "tractor beam" of Star Trek fame that works only at a microscopic scale. Single cells and small translucent particles can be trapped and held in three-dimensional space. The laser trap may also be used to measure the elasticity, distance moved, or force generated by single protein molecules. We are using the laser trap in combination with the motility assay to study the force and motion generated by myosin and the strength of single adhesion receptor bonds. Together, these molecules define the molecular underpinnings of many cell movements, and the molecular basis of many diseases.

We are studying four fundamental issues in cell movement. First, to understand the molecular basis of myocardial damage following ischemia, we are collaborating with Dr. Brent French to study the mechanics of myosin derived from mouse hearts after myocardial infarction. Second, in collaboration with Drs. Lawrence and Ley we are measuring the mechanics and kinetics of individual selectin adhesion bonds and membrane tethers, important in inflammation and the development of atherosclerosis. Using similar techniques, we are studying the single molecule mechanics of actin-myosin bonds. Finally, we are doing preliminary studies on the relationship between the motor proteins driving fast axonal transport and the genesis of Lou Gerig's Disease.

Selected Publications

Snook JH, Li J, Helmke BP, Guilford WH. Peroxynitrite inhibits myofibrillar protein function in an in vitro assay of motility. Free Radic Biol Med. 2008 Jan 1;44(1):14-23.

Paschall CD, Guilford WH, Lawrence MB. Enhancement of L-selectin, but not P-selectin, bond formation frequency by convective flow. Biophys J. 2008 Feb 1;94(3):1034-45.

Rao VS, La Bonte LR, Xu Y, Yang Z, French BA, Guilford WH. Alterations to myofibrillar protein function in nonischemic regions of the heart early after myocardial infarction. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H654-9.

Guo B, Guilford WH. Mechanics of actomyosin bonds in different nucleotide states are tuned to muscle contraction. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9844-9.

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