Directory > Faculty
Bruce D. Uhal,
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Professor. Ph.D. (Biochemistry) 1987, Saint Louis University.
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Area
of Research Interest [PDF]
Research interests: Lung epithelial stem
cell function; regulation of epithelial cell death (apoptosis);
molecular mechanisms of lung fibrogenesis and repair.
The
air sacs of the lungs (alveoli) contain specialized epithelial cells that
synthesize pulmonary surfactant, pump water and solutes out of the airspaces,
metabolize foreign compounds and exert control over local immune defense
mechanisms. These cells, called alveolar epithelial type II pneumocytes,
normally reside in the “corners” of the alveoli and also function as stem
cells which proliferate in response to injury and thereby repopulate the damaged
epithelial layer. A variety of studies suggest that failure of the type II cells
to repair the damaged epithelium is a critical step that leads to fibrotic lung
disorders, of which there are more than 100 separate classifications.
Uncontrolled proliferation of type II cells also can lead to lung cancers.
Knowledge of the function of these stem cells is therefore very important to our
understanding of both normal lung homeostasis and the pathogenesis of lung
diseases.
My
laboratory has been studying the stem cell function of type II cells and its
regulation in the pathogenesis of lung fibrosis through the use of experimental
animal models and lung cell culture systems. Recently we discovered that during
lung injury, type II cells and adjacent lung fibroblasts begin synthesizing the
vasoactive peptide angiotensin II, independently of the "endocrine"
renin-angiotensin system that functions within the vasculature to control blood
pressure. More importantly, we found that locally-synthesized angiotensin II is
a key regulator of apoptosis (cell suicide) in type II cells, and that blockade
of angiotensin function can both ameliorate the apoptosis of alveolar epithelial
cells and prevent the lung fibrosis that follows a variety of lung injuries.
Our
current work is focused on defining the factors that induce the expression of
the gene for angiotensinogen, the precursor of angiotensin II, within the
alveolar epithelium. We also are beginning to identify the epithelial-specific
converting enzymes and receptor signaling pathways responsible for the
generation of angiotensin and its ability to induce apoptosis in response to
pathophysiological stimuli. The information gained from these studies will
ultimately provide a foundation from which to design new strategies for
preventing epithelial cell death and for blocking the injuries that lead to lung
disease.
Publications
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