Don
Rockey, M.D.
Professor, Dept. of Medicine, Gastroenterology
Professor, Department of Cell Biology
Director, Liver Center |
My
basic research focus is in two major areas. First,
the
laboratory is actively examining cellular and molecular
mechanisms underlying hepatic fibrosis and cirrhosis.
We, and others, have identified the cellular element
(termed
a stellate cell) in the liver responsible for extracellular
matrix synthesis during liver wound healing. Thus,
a major
effort in the laboratory is to understand the mechanisms
underlying many of its typical cellular features.
For
example, we shown that the potent vasoactive peptide,
endothelin, regulates the stellate cell cytoskeleton,
and in addition stimulates stellate cells' synthesis
of
extracellular matrix proteins.
The second area of investigation is
in cell and molecular aspects of hepatic microvascular
blood flow. We have further demonstrated that stellate
cells possess unique contractile properties, and therefore
are likely to regulate sinusoidal blood flow. We have
also recently highlighted a unique endothelialopathy
in the injured liver; in the working model, vascular homeostastic
mechanisms involving endothelin and nitric oxide are
dysregulated after wound healing.
Selected Publications
Rockey DC, Chung JJ. Endothelin antagonism in experimental
hepatic fibrosis: Implications for endothelin in the pathogenesis
of wound healing. Journal of Clinical Investigation 98:1381-1388,
1996.
Shi Z, Wakil EA, Rockey DC. Strain-specific differences
in mouse hepatic wound healing are mediated by divergent
T helper cytokine responses. Proceedings of the National
Academy of Sciences: USA 94: 1066-10668, 1997.
Shao R, Yan W, Rockey DC. Regulation of endothelin production
by endothelin converting enzyme-1 in hepatic wound healing.
Journal of Biological Chemistry 274:3228-3234, 1999.
Yu Q, Shao R, Qian HS, George S, Rockey DC. Adenoviral
mediated gene transduction of neuronal NO synthase ameliorates
experimental portal hypertension. Journal of Clinical
Investigation 105:741-748, 2000.
Shao R, Shi Z, Gotwals PJ, Koteliansky VE, George J,Rockey
DC. Cell and Molecular Regulation of Endothelin-1 Production
during Hepatic Wound Healing. Molecular
Biology of the Cell Vol. 14, 2327–2341, June
2003. -PDF-
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