Immunology Graduate Group

Hydar Ali, Ph.D
Associate Professor, Pathology

Address: 240 South 40th Street, 346 Levy Building
Office Phone: (215) 573-1993
Lab Phone: (215) 573-8963
Fax: (215) 573-2050
Email: ali@path.dental.upenn.edu

Department of Pathology

Education:
Ph.D., University College, London, England
B.S., University College, London, England

Research Interests

G protein coupled Receptor Signaling in innate immunity and inflammatory diseases.

Research Summary

Our research focuses on two areas of signal transduction pathways in leukocytes. In the first, we are studying how phagocytic leukocytes mediate host defense against infection and also cause inflammatory diseases. The pathophysiologic effects of leukocytes are mediated via the activation of cell surface G protein coupled chemoattractant receptors for formylated peptides (fMLP) and platelet-activating-factor (PAF) to induce degranulation and chemokine gene expression. We are testing the hypothesis that fMLP and PAF-induced degranulation is inhibited via the modification of multiple components in the receptors' signaling pathways. We have already shown that receptor phosphorylation partially blocks both G protein activation and degranulation in leukocytes. We are testing the hypothesis that modification of phospholipase C (PLC ) by phosphorylation provides an additional mechanism for down-regulation of chemoattractant receptor-induced degranulation. We have recently shown that receptor phosphorylation, which provides a partial turn-off signal for degranulation, is absolutely essential for chemokine gene expression. This pathway does not require G protein activation. We have initiated studies to delineate the roles of G protein-independent signaling on chemoattractant receptor-induced transcription factor activation and chemokine gene expression in leukocytes.

In the second, we are studying the roles of G protein coupled receptors in the pathogenesis of asthma and allergic diseases. There is a substantial body of evidence that cross-linking of high affinity IgE receptors (Fc RI) on mast cells by antigen leads to the release of inflammatory mediators that play important roles in the pathogenesis of asthma and allergic diseases. Mast cells also express G protein coupled receptors for adenosine, the anaphylatoxins C3a, C5a and chemokines, RANTES and MIP-1 . We hypothesize that these receptors play important roles in the pathogenesis of asthma and allergic diseases by (a), regulating mediator release in antigen-stimulated mast cells and (b), by causing mediator release in cytokine-primed mast cells.

Recent Publications

Pirrung, M.C., Drabik, S., Ahamed, J., and Ali, H: Caged chemotactic peptides. Bioconj. Chem, 11, 679-681, 2000

Ali, H, Ahamed, J, Hernandez-Munain, C., Baron, J. L., Krangel, M. S. and Patel D. K. Chemokine production by G protein coupled receptor activation in a human mast cell line: Roles of ERK and NFAT. J. Immunol. 165, 7215-7223, 2000

Ahamed, J., Haribabu, B., and Ali, H. Cutting Edge: Differential regulation of chemoattracant receptor-induced degranulation and chemokine production by receptor phosphorylation. J. Immunol, 167, 3559-3563, 2001

Ahamed, J and Ali, H., Distinct roles of receptor phosphorylation, G protein usage and mitogen-activated protein kinase activation on platelet-activating-factor-induced leukotrience C4 generation and chemokine production. J. Biol. Chem. 277, 22685-22691, 2002

 

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