Sanford R. Simon
Ph.D., Rockefeller University, 1967
Associate Professor, Departments of Biochemistry and Cell Biology and Pathology
Research Interests: Biochemistry and cell biology of inflammatory cells
and their products
Acute and chronic inflammatory responses are important host defenses against
foreign substances or pathogens. These responses are largely mediated by
neutrophils and macrophages, which release proteases, cytokines, and a number
of other mediators of inflammation in the course of defending the host.
We study the mechanisms of action of serine proteases and metalloproteases
from activated neutrophils and develop specific inhibitors to control the
tissue destruction which may otherwise injure the host during an inflammatory
response. Our methods include biophysical probes of enzyme active sites
and kinetic measurements. We also work with a complete interstitial extracellular
matrix from rat smooth muscle cells which we label biosynthetically and
employ as a substrate for activated inflammatory cells and their proteases.
We also allow the smooth muscle cells to deposit their matrix on porous
membrane filters, which we then use to study invasive migration of neutrophils
and macrophages in response to chemotactic stimuli. To understand how inflammatory
cells communicate we study paracrine mechanisms of activation by cytokines,
using immunofluorescence and flow cytometry to measure levels of expression
of cell surface receptors and other marker proteins which are sensitive
to the state of activation of the cells. We also measure neutrophil and
macrophage phagocytic activity and release of oxidants by flow cytometry.
Ying, Q., Rinehart, A.R., Cheronis, J.C. and Simon, S.R. (1991) Inhibition
of human leukocyte elastase by ursolic acid: evidence for a hydrophobic
binding site for pentacyclic triterpenes. Biochem. J. 277: 521-526.
Matic, M. and Simon, S.R. (1991) TNF Release from LPS stimulated monocytes:
LPS tolerance in vitro. Cytokine 3:
576-583.
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