Leonidas C. Platanias, M.D., Ph.D. Professor of Medicine Deputy Director, Robert H. Lurie Comprehensive Cancer Center Signal Transduction For Interferons And Other Cytokines In Malignant Cells Curricula: Cancer Biology Pharmacology and Toxicology E-mail:   l-platanias@northwestern.edu

My research interests are in the field of cytokine-signaling in malignant cells. We have identified and characterized several novel signaling cascades activated by the Type I interferon receptor in leukemia and other neoplastic cells, including the insulin receptor substrate (IRS)-pathway, the Crk-pathway and the p38 Map kinase signaling cascade. A major interest of our group is to determine the mechanisms by which chronic myelogenous leukemia (CML) cells become refractory to the antiproliferative effect of interferons and the mechanisms of synergy between interferon and STI571. Other research areas in which my laboratory is actively engaged are the mechanisms of signal transduction of all-trans-retinoic acid (ATRA) and arsenic trioxide in acute promyelocytic leukemia. We also study the signaling mechanisms of regulation of normal hematopoiesis by myelosuppressive cytokines, including interferons, tumor necrosis factor-alfa and transforming growth factor-beta.

Publications:

Verma, A., Deb, D.K., Sassano, A., Uddin, S., Varga, J., Wickrema, A., and Platanias, L.C. (2002) Activation of the p38 Mitogen activated protein kinase mediates the suppressive effects of Type I interferons and transforming growth factor-b on normal hematopoiesis. J. Biol. Chem. 277:7726-7735.

Verma, A., Deb, D.K., Sassano, A., Kambhampati, S., Wickrema, A., Uddin, S., Mohindru, M., Van Besien, K., and Platanias, L.C. (2002)Cutting edge: Activation of the p38 Map kinase signaling pathway mediates cytokine-induced hematopoietic suppression in aplastic anemia. J. Immunol. 168:5984-5988.

Alsayed, Y., Uddin, S., Mahmud, N., Lekmine, F., Kalvakolanu, D.V., Minucci, S., Bokoch, G., and Platanias,L.C. (2001) Activation of Rac1 and the p38 Map kinase pathway in response to all-trans-retinoic acid. J. Biol. Chem. 272:4012-4019.

Mayer, I.A., Verma, A., Grumbach. I.M., Uddin, S., Lekmine, F., Ravandi, F., Majchrzak, B., Fujita, S., Fish, E.N., and Platanias, L.C. (2001) The p38 Map kinase pathway mediates the growth inhibitory effects of IFNa in BCR-ABL expressing cells. J. Biol. Chem. 276:28570-8577.

Alsayed, Y., Uddin, S., Ahmad, S., Majchrzak, B., Druker, B.J., Fish, E.N., and Platanias, L.C. (2000) Interferon g activates the C3G-Rap1 signaling pathway. J. Immunol. 164:1800-1806.

Uddin, S., Lekmine, F., Sharma, N., Majchrzak, B., Mayer, I., Young, P.R., Bokoch, G.M., Fish, E.N. and Platanias, L.C. (2000) The Rac1/p38 Map kinase pathway is required for IFNa-dependent transcriptional activation but not serine phosphorylation of Stat-proteins. J. Biol. Chem. 275:27634-27640.

Du, J., Alsayed, Y., Xin, F., Ackerman, S.J., and Platanias, L.C. (2000) Engagement of the CrkL adapter in interleukin-5 signaling in eosinophils. J. Biol. Chem. 275:33167- 33175.