Sergei V. Kotenko, Ph.D.
Research: Research in my lab is aimed to advance our knowledge of the complex role played by various cytokines in the regulation of the immune response to and in the pathogenesis of a number of diseases including cancer. Based on this knowledge several strategies are being developed to enhance the immune response against tumors and, therefore, help the immune system to combat cancer.
Sergey Smirnov, PhD
Zhiwei Yin, PhD
Ph.D., 1990, Institute for Genetics and Microorganisms M.S., 1985, Moscow Engineering Physics Institute
McCarthy, B.A., Mansour, A., Lin, Y.C., Kotenko, S.V., and Raveche, E. (2004) RNA Interference of IL-10 in Leukemic B-1 cells. Cancer Immun. 4, 6-22
Dumoutier, L., Tounsi, A., Michiels, T., Sommereyns, C., Kotenko S.V., and Renauld, J.C. (2004) Role of the Interleukin-28 Receptor Tyrosine Residues for Antiviral and Antiproliferative Activity of IL-29/IFN-l1: Similarities with Type I Interferon Signaling J. Biol. Chem. 279, 32269-32274
Sheikh, F., Baurin, V.V., Lewis-Antes, A., Shah, N.K, Smirnov, S.V., Anantha, S., Dickensheets, H., Dumoutier, L., Renauld, J.C., Zdanov, A., Donnelly, R.P., and Kotenko, S.V. (2004) IL-26 Signals Through a Novel Receptor Complex Composed of IL-20R1 and IL-10R2. J. Immunol. 172, 2006-2010
Ramesh, R., Mhashilkar, A.M., Tanaka, F., Saito, Y., Branch, C.D., Sieger, K., Mumm, J.B., Stewart, A.L., Boquio, A., Dumoutier, L., Grimm, E.A., Renauld, J.C., Kotenko, S., and Chada, S. (2003) MDA-7/IL-24 is a novel ligand that regulates angiogenesis via the IL-22 receptor. Cancer Res. 63, 5105-5113
Kotenko, S.V., Gallagher, G., Baurin, V.V., Lewis-Antes, A., Shen, M., Shah, N.K., Langer, J.A., Sheikh, F., Dickensheets, H., and Donnelly, R.P. (2003) Interferon- s mediate antiviral protection through a unique class II cytokine receptor complex. Nat. Immunol. 4, 69-77
Kotenko, S.V., Izotova, L.S., Mirochnitchenko, O.V., Esterova, E., Dickensheets, H., Donnelly R.P., and Pestka, S. (2001) Identification, Cloning and Characterization of a Novel Soluble Receptor That Binds IL-22 and Neutralizes Its Activity. J. Immunol. 166, 7096-7103
Kotenko, S.V., Izotova, L.S., Mirochnitchenko, O.V., Esterova, E., Dickensheets, H.., Donnelly, R.P., and Pestka, S. (2001) Identification of the Functional Interleukin-22 (IL-22) Receptor Complex: the IL-10R2 Chain (IL-10Rβ) Is a Common Chain of Both the IL-10 and IL-22 (IL-10-Related T Cell-Derived Inducible Factor, IL-TIF) Receptor Complexes. J. Biol. Chem. 276, 2725-2732
Kotenko, S.V., Saccani, S., Izotova, L.S., Mirochnitchenko, O.V., and Pestka, S. (2000) Human Cytomegalovirus Harbors Its Own Unique Interleukin-10 Homolog (cmvIL-10). Proc. Natl. Acad. Sci. USA 97, 1695-1700
Kotenko, S.V., Izotova, L.S., Mirochnitchenko, O.V., Lee, C., Pestka, S. (1999) The Intracellular Domain of IFN-αR2c Chain is Responsible for Stat Activation. Proc. Natl. Acad. Sci. USA 96, 5007-5012
Kotenko, S.V., Krause, C.D., Izotova, L.S., Pollack, B.P., Wu, W., and Pestka, S. (1997) Identification and Functional Characterization of a Second Chain of the Interleukin-10 Receptor Complex. EMBO J. 16, 5894-5903
Areas Of Interest
Development of cancer is a multi-step process. It is likely to be started with one point mutation which gives a single cell some kind of minor advantage - either increased rate of uncontrolled proliferation, or unresponsiveness to external signals commanding the cell to commit suicide (apoptosis). The immune system also reacts to and destroys the rebel and it?s progeny. However, in the rare events, one or more of the rebel?s offspring, in addition to the initial advantageous mutation, gain other beneficial mutations to protect themselves from the immune surveillance. And the battle between the controlling army of the immune system and protective forces of cells which are trying to become immortal, carries on. Therefore, the immune system is engaged in all steps of tumor development and progression, and the failure of the immune system to recognize and eliminate cancerous cells is a must for tumor survival and progression.
Many drugs and methods targeting tumors for distruction are constantly being developed and in trials for their effectiveness. However, it is unlikely that a single drug equally effective in fighting different cancers would be finally created, particularly because even a single tumor often represents a pool of cells which have accumulated different multiple mutations. The immune system, on the other hand, is the army of ?universal soldiers? which ideally should be able to deal with any type of cancer. In reality, however, the immune system, in the case of cancers, is not able to handle it on its own.
Research in my lab is aimed to advance our knowledge of the complex role played by various cytokines in the regulation of the immune response to and in the pathogenesis of a number of diseases including cancer. Based on this knowledge several strategies are being developed to enhance the immune response against tumors and, therefore, help the immune system to combat cancer.