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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
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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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