Eleanor M. Black Chair of Immunophysiology and Pharmaceutical Biotechnology
Professor of Pharmaceutical Sciences
Director, New England Inflammation and Tissue Protection Institute

Contact Information
   Office: 113 Mugar Hall
   Voice: 617.373.4157
   Fax: 617.373.5834
   Email: m.sitkovsky@neu.edu

Education
Ph.D., Moscow State University

Specializations
Biochemistry and Immunopharmacology

Major Research Areas
Pro-inflammatory cytokines are crucially important in the immune response and host defense against pathogens, but exceedingly intensive or prolonged inflammation processes represent the main cause of many different diseases. Molecular mechanisms, which terminate inflammation in vivo, are poorly understood. In our studies we explore basic and clinical implications of the following physiological loop (See Cartoon)

Diagram of physiological loop1. Inflammatory stimuli => 2. Local tissue hypoxia --> {?Hypoxia–induced transcription factors (HIF-1a, HIF-2)}? => 3. Accumulation of extracellular adenosine---> 4.signaling through G protein-coupled receptors on immune cells=> 5.OFF signaling to STOP secretion of pro–inflammatory cytokines=> 6.The Beginning of the End of Inflammation.

We have recently implicated this loop in acute inflammation processes (as described in our Dec.20, 2001 Nature paper, see references) and now we are studying or preparing to study the role of adenosine receptors in chronic inflammation in different mouse models of autoimmune diseases as well as the role of adenosine receptors in organ transplant rejection. In addition, the novel strategies are being developed to target the adenosine receptors for selective destruction of tumors.

Selected Publications
Ohta, A., Sitkovsky, M. Critical Role of G protein-coupled adenosine Receptors in Down Regulation of Inflammation and Prevention of Tissue Damage In Vivo. Nature. 414, 916-920, 2001.
This paper was highlighted in:
— Nature Reviews Drug Discovery 1, 2, p.99, 2002: "Putting the Brakes on Inflammation"
— NIH Press Release "Damping The Flames: Inflammation Control Mechanism Determined."Web page: http://www.nih.gov/news/pr/dec2001/niaid-19.htm

Lukashev, D. E., Caldwell, C. C., Chen, P., and Sitkovsky, M. V. Differential upregulation of expression of I.1 and I.2 mRNA isoforms of hypoxia-inducible factor-1alpha in activated T lymphocytes. HIF-1alpha is an immediate-early response gene. J.Biol.Chem. 276,52,48754-63, 2001.

Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1alpha -deficient chimeric mice. Kojima H, Gu H, Nomura S, Caldwell CC, Kobata T, Carmeliet P, Semenza GL, Sitkovsky MV. Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1alpha -deficient chimeric mice. Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2170-2174.

Caldwell, C. C., Kojima, H., Lukashev, D., Armstrong, J., Farber, M., Apasov, S., and Sitkovsky, M. V. Differential effects of physiologically relevant hypoxic conditions on T lymphocyte development and effector functions. J. Immunol. 167: 6140-6149, 2001.

Apasov, S. G., Blackburn, M. R., Smith, P. T., Kellems, R. E., and Sitkovsky, M. V. Adenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling. J. Clin. Invest. 108: 131-141, 2001.

Apasov, S. G., Chen, J-F., Smith, P. T., Schwarzschild, M. A., Fink, J. S., and Sitkovsky, M.V. Study of A2A adenosine receptor gene deficient mice reveals that adenosine analogue CGS 21680 possesses no A2A receptor-unrelated lymphotoxicity. Br. J. Pharmacol. 131: 43-50, 2000.

Armstrong, J. M., Chen, J-F., Schwarzschild, M. A., Apasov, S., Smith, P. T., Caldwell, C., Chen, P., Figler, H., Sullivan, G., Fink, S., Linden, J., and Sitkovsky, M. Gene dose effect reveals no Gs protein coupled A2A adenosine receptor reserve in murine T lymphocytes. Studies of cells from A2A receptor gene-deficient mice. Biochem. J. 354: 123-130, 2001.

Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115