Research Activities

Steven M Taffet, Ph.D. Professor of Microbiology and Immunology 2235B Weiskotten Hall Upstate Medical University 750 East Adams Street Syracuse, NY 13210 (315) 464-5419 Lab/Professional Web Site

Education and Clinical Training

Research Program and Department Affiliations

Research Interests

Research Abstract

Regulation of Gene Expression in Macrophages.

This study seeks to determine the molecular basis of macrophage activation. Macrophages can be stimulated with a variety of stimuli to a state of heightened microbicidal and tumoricidal activity defined as activated. As a consequence of this stimulation is an alteration in the expression of many genes. One of these genes, tumor necrosis factor alpha (TNF-alpha ), is of critical importance in the development of both antimicrobial activity and the killing of tumor cells by macrophages. TNF-alpha levels are increased by the addition of bacterial lipopolysaccharide (LPS) to macrophage cultures. Our recent studies have focused on an enhancer element in the third intron of TNF. This element includes the binding sites for the ets transcription factor, GABP. Studies have indicated that GABP is present in macrophage-like cell lines but is induced by interferon treatment in bone marrow-derived macrophage populations. This may indicate that one of the steps in maturation of macrophage precursors includes the induction of GABP.

Acidification based gating of the Cardiac Gap Junction (with M. Delmar)

This study will define the structures of the cardiac gap junction protein (Connexin 43, CX43) that are involved in the pH-based gating of this channel. Site-directed mutants or wild-type Cx43 are expressed in Xenopus laevis oocytes where the activity of the expressed channel is determined. Upon reduction of the pH below 6.7 the channel closes preventing the flow of ions between two cells. We have prepared mutations of the Cx43 protein that prevents this closure. Three regions have been defined that are involved in this regulation. Two of these regions aa260-aa300 and aa374-382 are in the carboxyl terminal cytoplasmic domain. A third region involves a histidine residue at the border between the second transmembrane region and the intracellular loop domain. The hypothesis being tested is that the carboxyl-terminal domain act as a ball on a chain that interacts with a receptor near the second transmembrane domain. This work may help us understand the basis for heart rhythm abnormalities.

Selected References

O‚Donnell, P.M. and Taffet, S.M. The Proximal Promoter Region Is Essential for Lipopolysaccharide Induction and Cyclic-AMP Inhibition of Mouse Tumor Necrosis Factor Alpha. Journal of Interferon and Cytokine Research 22:539-548 (2002).

Duffy, H.S., Sorgen , P., Girvin, M., O‚Donnell, P.M., Coombs, W., Taffet, S., Delmar, M., and Spray, D.C., pH-Dependent Intramolecular Binding and Structure Involving Cx43 Cytoplasmic Domains. J. Biol. Chem. 277:36706-14 (2002)

Publications - link to PubMed

This profile was last updated on 09/29/2008

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