Department of Radiation Oncology

Constantinos (Costas) Koumenis

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Constantinos (Costas) Koumenis, Ph.D.

Richard H. Chamberlain Professor of Research Oncology
Department: Radiation Oncology
Graduate Group Affiliations

Contact information
University of Pennsylvania, Perelman School of Medicine
3400 Civic Center Blvd., Bldg 421
Smilow Center for Translational Research, Room 8-124
Philadelphia, PA 19104-5156
Office: 215-898-0076
Fax: 215-898-0090
Lab: 215-898-0078
Education:
BS (Pharmacy with honors)
Aristotle University, Thessaloniki, Greece, 1989.
PhD (Biochemistry)
University of Houston, Houston, Texas, 1994.
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Description of Research Expertise

KEYWORDS:
Tumor Microenvironment, Tumor Metabolism, Integrated Stress Response, drug screens, radiosensitizers.

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.

My laboratory is primarily interested in two broad areas:

1. 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.

2. 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 accepting 2 new rotation students.

Selected Publications

Tameire Feven, Verginadis Ioannis I, Leli Nektaria Maria, Polte Christine, Conn Crystal S, Ojha Rani, Salas Salinas Carlo, Chinga Frank, Monroy Alexandra M, Fu Weixuan, Wang Paul, Kossenkov Andrew, Ye Jiangbin, Amaravadi Ravi K, Ignatova Zoya, Fuchs Serge Y, Diehl J Alan, Ruggero Davide, Koumenis Constantinos: ATF4 couples MYC-dependent translational activity to bioenergetic demands during tumour progression. Nat Cell Bio 21(7): 889-899, Jul 2019.

Bell BI, Koduri S, Salas Salinas C, Monslow J, Puré E, Ben-Josef E, Koumenis C, Verginadis II: Interleukin 6 Signaling Blockade Exacerbates Acute and Late Injury From Focal Intestinal Irradiation. Int J Radiat Oncol Biol Phys 103(3): 719-727, Mar 2019.

An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles. Ortiz A, Gui J, Zahedi F, Yu P, Cho C, Bhattacharya S, Carbone CJ, Yu Q, Katlinski KV, Katlinskaya YV, Handa S, Haas V, Volk SW, Brice AK, Wals K, Matheson NJ, Antrobus R, Ludwig S, Whiteside TL, Sander C, Tarhini AA, Kirkwood JM, Lehner PJ, Guo W, Rui H, Minn AJ, Koumenis C, Diehl JA, Fuchs SY: An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles. Cancer Cell 35(1): 33-45, Jan 2019.

Ojha R, Leli NM, Onorati A, Piao S, Verginadis II, Tameire F, Rebecca VW, Chude CI, Murugan S, Fennelly C, Noguera-Ortega E, Liu S, Xu X, Krepler C, Xiao M, Xu W, Wei Z, Frederick DT, Boland G, Mitchell TC, Karakousis GC, Schuchter LM, Flaherty KT, Zhang G, Herlyn M, Koumenis C, Amaravadi RK.: ER Translocation of the MAPK Pathway Drives Therapy Resistance in BRAF-Mutant Melanoma. Cancer Discov 9(3): 396-415, Dec 2018.

Baumann BC, Verginadis II, Zeng C, Bell B, Koduri S, Vachani C, MacArthur KM, Solberg TD, Koumenis C, Metz JM: Assessing the Validity of Clinician Advice That Patients Avoid Use of Topical Agents Before Daily Radiotherapy Treatments. JAMA Oncol 4(12): 1742-1748, Dec 2018.

Bi Y, Verginadis II, Dey S, Lin L, Guo L, Zheng Y, Koumenis C.: Radiosensitization by the PARP inhibitor olaparib in BRCA1-proficient and deficient high-grade serous ovarian carcinomas. Gynecol Oncol 150(3): 534-544, Sep 2018.

Walton ZE, Patel CH, Brooks RC, Yu Y, Ibrahim-Hashim A, Riddle M, Porcu A, Jiang T, Ecker BL, Tameire F, Koumenis C, Weeraratna AT, Welsh DK, Gillies R, Alwine JC, Zhang L, Powell JD, Dang CV: Acid Suspends the Circadian Clock in Hypoxia through Inhibition of mTOR. Cell 174(1): 72-87, Jun 2018.

Nguyen HG, Conn CS, Kye Y, Xue L, Forester CM, Cowan JE, Hsieh AC, Cunningham JT, Truillet C, Tameire F, Evans MJ, Evans CP, Yang JC, Hann B, Koumenis C, Walter P, Carroll PR, Ruggero D: Development of a stress response therapy targeting aggressive prostate cancer. Sci Transl Med 10(439), May 2 2018.

Wang Y, Xu H, Liu T, Huang M, Butter PP, Li C, Zhang L, Kao GD, Gong Y, Maity A, Koumenis C, Fan Y: Temporal DNA-PK activation drives genomic instability and therapy resistance in glioma stem cells. JCI Insight 3(3), Feb 8 2018.

Bu Y, Yoshida A, Chitnis N, Altman BJ, Tameire F, Oran A, Gennaro V, Armeson KE, McMahon SB, Wertheim GB, Dang CV, Ruggero D, Koumenis C, Fuchs SY, Diehl JA: A PERK-miR-211 axis suppresses circadian regulators and protein synthesis to promote cancer cell survival. Nat Cell Bio 20(1): 104-115, Jan 2018.

Brady LK, Wang H, Radens CM, Bi Y, Radovich M, Maity A, Ivan C, Ivan M, Barash Y, Koumenis C: Transcriptome analysis of hypoxic cancer cells uncovers intron retention in EIF2B5 as a mechanism to inhibit translation. PLoS Biol 15(9): e2002623, Sep 29 2017.

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Last updated: 08/27/2019
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