 Richard
Tsika, PhD
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Professor
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Associate Professor,
Biochemistry, College of Medicine
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Investigator,
Dalton Cardiovascular Research Center
Email:
TsikaR@missouri.edu
PhD—University of California-Irvine
Research Interests: Muscle
molecular biology
Teaching: Muscle biology
My laboratory is elucidating the molecular
mechanisms that control gene transcription
in adult-stage skeletal muscle. It has been
well documented that the phenotype of adult-stage
skeletal muscle can be profoundly altered
in response to diverse modes of neuromuscular
activity such as mechanical overload (MOV)
and non-weight-bearing activity (NWB). To
better understand this phenotypic plasticity
in molecular terms, we are studying the
bmyosin heavy chain (bMyHC) gene as a model
system since bMyHC expression is primarily
restricted to slow-type I fibers in adult-stage
muscle but can be induced in fast-type II
fibers following MOV. Further, bMyHC expression
is decreased in slow-type I fibers in response
to NWB activity. This observation is important
since functionally myosin serves a chemomechanical
role during muscle contraction, therefore,
the amount and type of myosin expressed
within the sarcomeres of a given muscle
type is an important determinate of its
physiological function.
Three major areas of study are
ongoing in the laboratory:
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The in vivo identification
of DNA regulatory elements involved in
bMyHC fiber-type expression and its altered
expression in response to MOV or NWB.
Critical fiber-type and perturbation specific
cis-acting regulatory elements are identified
by performing a promoter deletion and
mutational analysis using transgenic mice
and the experimental paradigms of a) decreased
mechanical load using a ground based model
of simulated zero gravity (results in
fiber-type shift and muscle atrophy),
b) increased mechanical load induced by
synergist ablation (results in fiber-type
shift and muscle hypertrophy),
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The isolation and molecular
characterization of the nuclear transcription
factors that bind to these elements, and
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The identification of
cellular signaling pathways that are activated
during fiber-type shifts.
The lab has recently focused on
two pertinent questions that have
evolved from our results obtained from these
three major research areas to date:
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Is adult stage muscle
plasticity (adaptations) a recapitulation
of development?
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Are the cis-acting elements
and trans-acting factors that are involved
in the hypertrophic and phenotypic response,
the same for both cardiac and skeletal
muscle? Our current findings that lend
insight into these critical questions
are described in the publications below.
Our immediate and future work will focus
on the further delineation of the molecular
mechanisms that control bMyHC expression.
Collectively, our past and future studies
are likely to identify new molecular and
cellular targets important for the development
of new therapeutic approaches directed against
muscular dysfunction associated with disease,
certain illnesses and space flight. This
is important to all scientists concerned
with muscle function, specialization, and
adaptation.
Publications:
Tsika, R. W., J. J. McCarthy, Ys. Ou, N.
Karasseva, M. Liao and G. L. Tsika. Role
of bMyosin Heavy Chain Nuclear Factor of
Activated T-Cells, Muscle-CAT, E-box and
A/T-rich elements in Slow Muscle and Simulated
Zero Gravity Regulation. J. Biol. Chem.
submitted 2001.
Vyas, D., J. J. McCarthy, G. L. Tsika and
R. W. Tsika. Multiprotein Complex Formation
at the bMyosin Heavy Chain Distal Muscle
CAT Element Correlates with Slow Muscle
Expression but Not Mechanical overload Responsiveness.
J. Biol. Chem. 276, 1173-1184, 2001.
McCarthy JJ, Vyas D, Tsika G, Tsika RW.
Segregated perturbation-specific regulatory
elements direct bMyHC expression in response
to altered muscle activity. J. Biol. Chem.
274:(20), 14270-14279, 1999.
Vyas, D., J. J. McCarthy, and R. W. Tsika.
Nuclear protein binding at the b-Myosin
Heavy Chain A/T-rich element is enriched
following increased skeletal muscle activity.
J. Biol. Chem. 274, 30832-30842, 1999.
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