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Venkateshwar G. Keshamouni, Ph.D.
Associate Professor,
Division of Pulmonary & Critical Care Medicine

vkeshamo@umich.edu


Current Research

Interactions between cancer cells and tumor associated host immune cells initiate and maintain tumor immune tolerance which eventually predominates and mitigates the effective host immune response.  The nature of the interactions between cancer cells and immune cells, and the molecular mechanisms underlying tumor immune tolerance is poorly understood. As part of its tumor promoting effects, TGF-b has a broad influence on the immune system through cross-talk with several immunomodulatory signaling pathways  including Toll-like receptors (TLRs) signaling. TLRs recognize non-self pathogen associated molecular patterns to trigger innate immune responses. In addition, TLRs can also recognize several endogenous danger associated molecules including heat shock proteins, double stranded DNA, and components of extracellular matrix. Tumor microenvironments are rich in such molecules that can potentially trigger anti-tumor immune responses. Our group is interested in investigating potential TGF-b mediated mechanisms which help tumor cells to circumvent TLR-mediated anti-tumor responses and identify molecular targets that mediate these mechanisms for prevention and treatment of lung cancer.

           
Representative Publications

Cavassani KA, Carson WF 4th, Moreira AP, Wen H, Schaller MA, Ishii M, Lindell DM, Dou Y, Lukacs NW, Keshamouni VG, Hogaboam CM, Kunkel SL. The post sepsis-induced expansion and enhanced function of regulatory T cells create an environment to potentiate tumor growth. Blood. 2010 Jun 3;115(22):4403-11. Epub 2010 Feb 3.

Standiford TJ, Kuick R, Bhan U, Chen J, Newstead M, Keshamouni VG. TGF-β-induced IRAK-M expression in tumor-associated macrophages regulates lung tumor growth. Oncogene. 2011 Jan 31. [Epub ahead of print]  PMID: 21278795

Reka AK, Kurapati H, Narala VR, Bommer G, Chen J, Standiford TJ, Keshamouni VG. Peroxisome proliferator-activated receptor-{gamma} activation inhibits tumor metastasis by antagonizing Smad3-mediated epithelial-mesenchymal transition Mol Cancer Ther. 2010 Dec;9(12):3221-32. PMID: 21159608

Reka A, Kuick R, Kurapati H, Standiford TJ, Omenn GS, Keshamouni VG. Identifying Inhibitors of Epithelial-mesenchymal Transition by Connectivity-map Based Systems Approach. J Thoracic Oncology 2011 (in press)

 

 

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