RESEARCH INTERESTS: Delineation of mechanisms of resistance to tumor microenvironmental stress, with emphasis on the Unfolded Protein Response in cancer. Development of small molecule agents to target these mechanisms as novel targeted modalities. Development of novel radiosensitizers.
KEYWORDS: Tumor Microenvironment, Tumor Metabolism, Integrated Stress Response, drug screens, radiosensitizers.
RESEARCH DETAILS: My laboratory is primarily interested in two broad areas:
A. To understand the mechanisms by which components of the microenvironment (e.g. hypoxia, low nutrient availability) interact with cellular survival/apoptotic pathways to produce a more resistant tumor phenotype. Once we understand the regulation and function of these survival pathways, we then design cell-based and assays to screen small molecule libraries for compounds that inhibit these processes and test them alone or in combination with genotoxic agents in several animal tumor models.
B. To increase the therapeutic effectiveness of ionizing radiation (IR) by either employing existing compounds with relatively safe toxicity profiles or employ screening strategies to identify novel and potent radiation sensitizers. We are also interested in developing novel delivery approaches for such compounds, such as biocompatible nanoparticles.
ROTATION PROJECTS: Currently the lab is not accepting any new rotation students
Steven Tuttle, Ph.D., Senior Res. Associate
Souvik Dey, Ph.D., Postdoctoral Fellow
Stacey Lehman, CAMB Graduate Student (CB)
Carly Sayers, Pharmacology Graduate Student
Natalie Daurio, Pharmacology Graduate Student
Feven Tameire, Stacey Lehman, CAMB Graduate Student (CB)
David Guttmann, Medical Student (MTR program candidate)
Yi Cheng, Research Specialist D
Yichen (Ethan) Song, Undergraduate Researcher
Ma XH, Piao SF, Dey S, McAfee Q, Karakousis G, Villanueva J, Hart LS, Levi S, Hu J, Zhang G, Lazova R, Klump V, Pawelek JM, Xu X, Xu W, Schuchter LM, Davies MA, Herlyn M, Winkler J, Koumenis C, Amaravadi RK.: Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. J Clin Invest 124(3): 1406-17, Mar 2014.
Guttmann D, Hart L, Du K, Seletsky A, Koumenis C: Inhibition of Hsp27 radiosensitizers head and neck cancer by modulating DNA repair. Intl. J. Radiat Oncol Biol Phys 87(1): 168-75, Sep 2013 Notes: granted supported.
Dey S, Tameire F, Koumenis C: PERK-ing up autophagy during MYC-induced tumorigenesis. Autophagy 9(4): 612-4, Apr 2013.
Sayers CM, Papandreou I, Guttmann DM, Maas NL, Diehl JA, Witze ES, Koong AC, Koumenis C: Identification and characterization of a potent activator of p53-independent cellular senescence via a small-molecule screen for modifiers of the integrated stress response. Mol Pharmacol 83(3): 594-604, Mar 2013.
Hart LS, Cunningham JT, Datta T, Dey S, Tameire F, Lehman SL, Qiu B, Zhang H, Cerniglia G, Bi M, Li Y, Gao Y, Liu H, Li C, Maity A, Thomas-Tikhonenko A, Perl AE, Koong A, Fuchs SY, Diehl JA, Mills IG, Ruggero D, Koumenis C: ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth. J Clin Invest 122(12): 4621-34, Dec 2012.
Cerniglia GJ, Karar J, Tyagi S, Christofidou-Solomidou M, Rengan R, Koumenis C, Maity A: Inhibition of autophagy as a strategy to augment radiosensitization by the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235. Mol Pharmacol 82(6): 1230-40, Dec 2012.
Chitnis NS, Pytel D, Bobrovnikova-Marjon E, Pant D, Zheng H, Maas NL, Frederick B, Kushner JA, Chodosh LA, Koumenis C, Fuchs SY, Diehl JA: miR-211 is a pro-survival micro-RNA that regulates chop expression in a PERK-dependent manner. Mol Cell 48(3): 353-64, Nov 2012.
Bhattacharya S, Huangfu W-C, Dong G, Qian J, Baker D P, Karar J, Koumenis C, Diehl J A, Fuchs S Y: Anti-tumorigenic effects of Type 1 interferon are subdued by integrated stress responses. Oncogene Oct 2012 Notes: Epub ahead of print.
Karar J, Cerniglia GJ, Lindsten T, Koumenis C, Maity A: Dual PI3K/mTOR inhibitor NVP-BEZ235 suppresses hypoxia-inducible factor (HIF)-1α expression by blocking protein translation and increases cell death under hypoxia. Cancer Biol Ther 13(11): 1102-11, Sep 2012.
Tuttle S, Hertan L, Daurio N, Porter S, Kaushick C, Li D, Myamoto S, Lin A, O'Malley BW, Koumenis C: The chemopreventive and clinically used agent curcumin sensitizes HPV (-) but not HPV (+) HNSCC to ionizing radiation, in vitro and in a mouse orthotopic model. Cancer Biol Ther 13(7): 575-84, May 2012.
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Last updated: 04/02/2014
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