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Member Information
Helen Korchak, PhD
Research Professor, Pediatrics and Biochemistry/Biophysics
Office Phone: 215-590-2136
Office Fax: 610-525-1190
Email: korchak@email.chop.edu
Website(s):
Education: PhD 1962, Tufts University - Physiology
Keywords: Neutrophil degranulation, O2 generation, phosphoinositide remodelling, antisense and PKC deletion, integrins, cytokines, TNF receptor
Research and/or Clinical Interests:
Signal transduction for oxygen radical production and exocytosis in phagocytic cells.
Summary:
Research in the Laboratory is aimed at elucidating the positive and negative signalling mechanisms for phagocytic cell functions such as degranulation and the generation and release of toxic oxygen species. These functions are important in the killing of microorganisms as well as in the tissue damage of inflammation. Assembly of signalling elements is triggered by ligand interaction with its receptor. The signalling complex then triggers end responses such as oxygen radical generation and release of granule contents. Receptor ligand interaction also triggers a negative feedback loop which elicits receptor downregulation. Signalling for activation of neutrophils has been proposed to require interaction of protein kinase C ~PKC, ~PKC and ~-PKC. Triggering of calcium movements and activation of protein kinase C requires remodelling of membrane phospholipids. A novel cofactor for nPKC, long chain fatty acyl CoA has been defined and its generation and mechanism of action are being elucidated. Different lipid sources and modes of regulation of diglyceride generation are also under investigation as a key to regulating protein kinase C activation. Activated neutrophils also generate phosphatidyl inositol 3,4,5 trisphosphate (PIP3) which is now thought to regulate some isotypes of protein kinase C including ~-PKC. The regulation of Pl-3kinase and its association with other signalling elements is under investigation.
Representative Publications:
Majumdar, S., Kane, L.H., Rossi M.W., Volpp, B.D., Nauseef, W.M. and Korchak, H.M. Protein kinase C isotypes and signal-transduction in neutrophils: selective substrate specificity of Ca-dependent B-PKC and novel Ca-independent nPKC. Bioch. Biophys. Acta 1_: 276-286 (1993)
Korchak, H.M., Kane, L.H., Rossi, M.W. and Corkey, B.E. Long chain acyl coenzyme A and signalling in neutrophils: an inhibitor of acyl coenzyme A synthetase, Triacsin C, inhibits superoxide anion generation and degranulation by human neutrophils. I. Biol. Chem. 269: 30281-30287 (1994)
Kilpatrick, L.E., Jacabovics, E., McCawley, LJ., Kane, L.H. and Korchak, H.M. Cromolyn inhibits assembly of the NADPH oxidase and superoxide anion generation by human neutrophils. I. Immunol. 154: 3429-3436 (1995)
