E. Kraus, M.D.
(Internal Medicine, Duke University)
Departments of Cell Biology and Medicine
Programs: Cell and Molecular Biology, Developmental Biology,
Cell Interactions and Differentiation
overall goal of our work is directed at gaining a better
understanding of cellular signaling pathways and mechanisms
responsible for the adaptive responses of skeletal muscle
to normal physiologic stimuli - such as exercise training
- and to maladaptive responses to pathophysiologic stimuli
- such as in congestive heart failure, skeletal muscle
atrophy associated with chronic spaceflight and aging.
We are using human studies, animal models and in vitro
models of exercise to address these scientific questions.
In this work, we have implicated signaling pathways involving
cAMP in the responses of skeletal muscle to long term
exercise training. We have found that gene expression
in skeletal muscle in congestive heart failure is altered
in a maladaptive fashion consistent with less effective
exercise tolerance and long term disability associated
with this condition. We have undertaken exercise training
studies in human subjects designed to address questions
about mechanisms of exercise training responses in skeletal
muscle in normal subjects and those with chronic heart
failure. Our in vitro models are designed to explore whether
mechanical deformation of skeletal muscle cells (mechano-transduction)
are responsible for some of the skeletal muscle responses
to changes in contractile activity. We are investigating
transduction of signals generated at the sarcolemmal membrane
into signals for alternation of proliferation and gene
expression in the nucleus in response to mechanical deformation.
Trainees in this laboratory acquire skills of molecular
biology and an understanding of how molecular tools can
be applied to the study of cellular and physiologic processes.
Duke University Medical Center
Durham, NC 27710
Duscha BD, Kraus WE, Keteyian SJ, Sullivan MJ, Green HJ,
Schachat FH, Pippin AM, Brawner BS, Blank JM, Annex BH.
Capillary density of skeletal muscle: A contributing mechanism
for exercise intolerance in class II-III chronic heart
failure independent of other peripheral mechanisms. J
Am Coll Cardiol 33(7): 1956-63, 1999.
Collinsworth AM, Torgan CE, Nagda S, Rajalingam R, Kraus
WE, Truskey GA. Physical orientation of mammalian skeletal
muscle in response to a unilateral stretch. Cell Tiss.
Res. 302 (2): 243-251, 2000.
Torgan CE, Burge SS, Collinsworth AM, Truskey GA, Kraus
WE. Differentiation of mammalian skeletal muscle cells
cultured on microcarrier beads in a rotating cell culture
system. Molecular and Biological Engineering and Computing
38 (Cell Engin): 583-590, 2000.
Slentz DH, Truskey GA, Kraus WE. Effects of chronic exposure
to simulated microgravity on skeletal muscle cell proliferation
and differentiation. In Vitro, 2001. (in press).
Bill Kraus, MD (Lab Dir.): Skeletal muscle responses to
exercise in health and disease.
Milton Campbell, MS (Research Analyst): Regulation of
metabolic gene expression in skeletal muscle.
Dorothy Slentz, MS (Research Analyst): Regulation of muscle
proliferation and differentiation in simulated microgravity.
Deborrah Muoio, PhD (Post-Doc): Metabolic gene regulation
in skeletal muscle: human studies.
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