Professor and Director of New England Inflammation and Tissue Protection Institute
Biochemistry and Immunopharmacology
Department of Biology
113 Mugar Life Sciences
360 Huntington Avenue
Boston, MA 02115 USA
- PhD, Moscow State University, Biochemistry and Biophysics
- MS, Moscow State University, Biophysics and Physiology
- Eleanor W. Black Chair and Professor, Immunophysiology and Pharmaceutical Biotechnology
- Presidential Scholar, Dana-Farber Cancer Institute, Cancer Vaccine Center, Harvard Institutes of Medicine
Other Professional Activities
- Design of clinical trials on immunotherapy of patients with lung, prostate, melanoma, and ovarian cancers.
The immediate focus of research is on cancer immunotherapy and prevention of iatrogenic complications due to elimination of the hypoxia-adenosinergic pathway.
A) Cancer immunotherapy is complementary to surgery, radiotherapy or chemotherapy. However, malignant cells can create a self-protective, tumor microenvironment (TME) that inhibits anti-tumor T cells. It is established that tumor cells are protected from anti-tumor T cells by the Hypoxia-Adenosinergic mechanism, which is triggered by very low local tumor tissue oxygen tension (i.e. hypoxia) and tumor hypoxia-produced extracellular adenosine. The key molecules of this immunosuppressive mechanism are a) cAMP-elevating A2A and, possibly, A2B adenosine receptors (A2AR/A2BR) and b) Hypoxia Inducible transcription Factor 1 alpha (HIF-1a). Preclinical testing suggests a promising novel approach that may prevent the inhibition of anti-tumor T cells and thereby improve the tumor rejection and cancer patients’ survival by eliminating the tumor protection by this Hypoxia-Adenosinergic mechanism.
B) While the Hypoxia-Adenosinergic tissue protection should be eliminated in order to enhance cancerous tissue destruction, it is a life saving mechanism when it protects normal tissues. It is shown that routinely and widely-used supplemental oxygen eliminates the Hypoxia-adenosinergic protection and thereby exacerbates acute lung inflammation. A novel supplemental oxygen protocol is suggested to allow safe oxygen without exacerbation of collateral inflammatory damage.
I have taught “Engineering Inflammation” and prepared the course “Careers in Medicine”.
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- Kincaid R, Takayama H, Billingsley M, Sitkovsky M. Differential expression of calmodulin-binding proteins in B-, T-lymphocytes and thymocytes. Nature 1987;330:176-8.
- Trenn G, Takayama H, Sitkovsky MV. Antigen receptor regulated exocytosis of cytolytic granules may not be required for target cell lysis by cytotoxic T-lymphocytes. Nature 1987;330:72-4.
- Sitkovsky MV, Paul WE. Immunology. Global or directed exocytosis? Nature 1988;332:306-7.
- Huang S, Apasov S, Koshiba M, Sitkovsky, M: Role of A2a adenosine receptor-mediated signaling in inhibition of T cell activation and expansion. Blood 1997;90:1600-10.
- Kojima H, Gu H, Nomura S, Caldwell CC, Kobata T, Carmeliet P, Semenza G, Sitkovsky MV. Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor-1 alpha deficient chimeric mice. Proc Natl Acad Sci USA 2002;99:2170-4.