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Andrzej Ptasznik, MD,PhD Medline
search Tel: (215) 573-4804 Residency: Internal Medicine, Central Clinical Hospital in Warsaw and District Hospital in Szczecin, Poland. Postdoctoral Training: Biochemistry/Immuno-hematology, Department of Immunology, The Scripps Research Institute, La Jolla, California. Research Interests My long standing interest has been aimed at identifying, testing and targeting signaling pathways in progenitor cells, in particular cells of hematopoietic and endocrine systems. We were one of the first to discover a crosstalk pathway between G protein-coupled receptors (GPCRs) and receptor tyrosine kinase (RTK) pathways. More precisely, we demonstrated that GPCRs regulate Shc/Ras-MAPK cascade via Lyn, a Src family kinase, in human leukocytes. This work, and that of others, provided a mechanistic explanation for the process of MAPK activation by a number of G protein-linked receptor systems in various tissues. We followed up on this series of studies and ultimately our work has also helped define the role of various isoforms of a PI 3-kinase in the formation of the critical second messenger molecule phosphatidylinositol 3,4,5-trisphosphate. This issue was of importance for understanding the actual signaling mechanisms that couple GPCRs to the generation of active oxidants and chemotaxis for the purpose of bacterial killing by normal leukocytes. More recently, we have demonstrated in human leukemia cells how over-active oncoproteins disrupt Src kinases-dependent and PI 3-kinase-mediated chemokine signaling pathways. We postulate that disruption of these pathways is responsible for abnormal circulation of transformed progenitor cells in the body in various types of leukemias and lymphomas. Based on these findings, we have recently formed the basis for a new therapeutic approach against hematological malignancies by targeting Src family kinases through RNA interference (RNAi) technology. Relevant Publications and Patents Ptasznik, A., Traynor-Kaplan, A., and Bokoch, G.M. (1995) G-protein coupled chemoattractant receptors regulate Lyn tyrosine kinase-Shc adapter protein signaling complexes in human leukocytes. J. Biol. Chem. 270: 19969 Ptasznik, A., Prossnitz, E.R., Yoshikawa, D., Smrca, A.,Traynor-Kaplan, A., and Bokoch, G.M. (1996) A tyrosine kinase signaling pathway accounts for the majority of phosphatidylinositol 3,4,5-trisphosphate formation in chemoattractant-stimulated human neutrophils. J. Biol Chem. 271: 25204 Ptasznik, A., Beattie, G.M., Mally, M.I., Cirulli, V., Lopez, A., and Hayek, A. (1997) Phosphatidylinositol 3-kinase is a negative regulator of cellular differentiation. J. Cell Biol. 137 : 1127 Ptasznik A., Urbanowska E, Chinta S., Costa MA, Katz BA., Stanislaus MA, Demir G., Linnekin D, Pan ZK., Gewirtz AM. (2002) Crosstalk between BCR/ABL oncoprotein and CXCR4 signaling through a Src family kinase in human leukemia cells. J. Exp Med. 196(5):667 Ptasznik, A., Nakata, Y., Kalota, A., Emerson, S.G., Gewirtz, A.M. (2004) Short interfering RNA (siRNA) targeting the Lyn kinase induces apoptosis in primary, and drug-resistant, BCR-ABL1(+) leukemia cells. Nature Med. 10(11):1187 Ptasznik A., Hayek A, Beattie G., United States Patent entitled "PI 3-kinase inhibitors as stimulators of endocrine differentiation", Patent Number: 6,413,773 |
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