Regulation of gene expression in striated myocytes.
The 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 occurs in exercise training – and to
maladaptive responses to pathophysiologic stimuli
– such as occurs 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. One of our underlying assumptions is that
much of the signaling in response to exercise occurs
as mechanotransduction from the external environment
to the nucleus, resulting in altered gene expression
for metabolic, structural and signaling proteins.
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. For example, we
use a unilateral stretch device of our own design
to explore changes induced by stretch and modifications
of our design of a rotating cell culture system to
explore changes induced by simulated microgravity.
Students in our laboratory learn the essentials of
molecular biology techniques in the context of addressing
mechanistic questions of interest to the laboratory.
Students are also instructed in scientific writing
and presentation and learn how to ask meaningful scientific
questions and pose hypotheses in order to develop
and write scientific applications.
Another focus of our work is physiologic examination
of exercise effects in human subjects in clinical
trials of exercise training in normal individuals,
in individuals at risk of disease (such as pre-diabetes),
and in individuals with disease (such as coronary
heart disease and congestive heart failure). We explore
skeletal muscle adaptation at the protein and gene
expression levels. A final area is exploration of
genetic determinates of disease risk in human subjects.
We conduct studies of early onset cardiovascular disease
(GENECARD), congestive heart failure (HF-ACTION) and
metabolic syndrome (CHANGES). We are involved in exploring
analytic models of predicting disease risk using established
and new statistical methodology.
