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Training (non-faculty)
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1990-1991: Research Associate, Dept. Surgery,
State University of New York at Buffalo |
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1991-1997: Senior Scientist, Director of
Cardiothoracic Surgery Research Laboratory, Dept. of
Surgery, University of Wisconsin School of Medicine,
Madison |
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Faculty
Appointments
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1997-2002:
Associate Professor of Surgery (Primary Appointment),
Associate Professor of Physiology (Secondary
Appointment) University of Kentucky College of Medicine,
Lexington |
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2002-2006:
Professor of Surgery, Associate Professor of Physiology,
University of Kentucky College of Medicine |
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1997-2006:
Director of Research, Department of Surgery, University
of Kentucky College of Medicine |
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2006-present:
Professor, Dept. Physiology, Wayne State University |
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Focus of Research
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My
laboratory’s research is focused on the
role of G protein coupled receptor (GPCR)
regulation of cardiac function and response
to stress, such as myocardial
ischemia-reperfusion. Our primary focus
is the adenosine receptor system, which
is composed of four receptor subtypes.
All four subtypes are expressed to
varying degrees in cardiac myocytes,
fibroblasts, and endothelial cells in
mammalian myocardium. We are currently
examining interactions among these
receptor subtypes in the reduction of
myocardial ischemia-reperfusion injury,
as well as interactions among adenosine
receptors and other GPCR, such as
beta-adrenergic receptors and opioid
receptors. These interactions are being
examined with adenosine A1, A2A,
and A2B receptor knockout
mice using the isolated perfused mouse
heart preparation and isolated
ventricular myocytes. Since these three
subtypes can activate similar protein
kinases, our working hypothesis is that
receptor crosstalk optimizes these
signaling mechanisms in specific
subcellular fractions. Current studies
are investigating adenosine receptor
subtype modulation of protein kinases (PKC
isoforms and mitogen activated protein
kinases (MAPK)) and protein phosphatases
in the plasma membrane and the
subsarcolemmal pool of mitochondria.
In contrast to cardiac myocytes where
the A1 receptor subtype
exhibits the greatest expression, A2A
and A2B receptors are
expressed at much higher levels in
cardiac fibroblasts. Studies in
cultured cardiac fibroblasts from WT and
KO mouse are examining the roles of
these two receptor subtypes in the
normal heart and in post-myocardial
infarction (MI) hearts induced by
permanent coronary artery occlusion.
These studies are designed to determine
the role of adenosine receptors in
post-MI ventricular remodeling. Further
studies are investigating adenosine
receptor subtype modulation of
b-adrenergic
receptor subtype induced increases in
cardiac contractility and differences in
b-adrenergic
receptor signaling in male and female
hearts. |
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