Constantinos Koumenis, Ph.D.
Richard H. Chamberlain Professor of Radiation 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
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
Fax: 215-898-0090
Lab: 215-898-0078
Publications
Links
Search PubMed for articles
Program Project Grant (P01): Unfolded Protein Response in Cancer
Program Project Grant P01: Translational Studies in FLASH Particle Radiotherapy
Lab Web page
Search PubMed for articles
Program Project Grant (P01): Unfolded Protein Response in Cancer
Program Project Grant P01: Translational Studies in FLASH Particle Radiotherapy
Lab Web page
Education:
BS (Pharmacy with honors)
Aristotle University, Thessaloniki, Greece, 1989.
PhD (Biochemistry)
University of Houston, Houston, Texas, 1994.
Permanent linkBS (Pharmacy with honors)
Aristotle University, Thessaloniki, Greece, 1989.
PhD (Biochemistry)
University of Houston, Houston, Texas, 1994.
Description of Research Expertise
KEYWORDS:Tumor Microenvironment, Tumor Metabolism, Integrated Stress Response, drug screens, radiosensitizers.
RESEARCH INTERESTS: Develop novel, more physiologically relevant animal models of incidental radiation damage and employing novel radiation delivery technologies (such as FLASH RT) in order to develop biomarkers of response to RT and to improve the therapeutic window of RT.
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
Ni H, Reitman ZJ, Zou W, Akhtar MN, Paul R, Huang M, Zhang D, Zheng H, Zhang R, Ma R, Ngo G, Zhang L, Diffenderfer ES, Motlagh SAO, Kim MM, Minn AJ, Dorsey JF, Foster JB, Metz J, Koumenis C, Kirsch DG, Gong Y, Fan Y.: FLASH radiation reprograms lipid metabolism and macrophage immunity and sensitizes medulloblastoma to CAR-T cell therapy. Nat Cancer. Page: 10.1038/s43018-025-00905-6, Feb 2025.Verginadis II, Citrin DE, Ky B, Feigenberg SJ, Georgakilas AG, Hill-Kayser CE, Koumenis C, Maity A, Bradley JD, Lin A.: Radiotherapy toxicities: mechanisms, management, and future directions. Lancet 405: 338-352, Jan 2025.
Amit U, Uslu U, Verginadis II, Kim MM, Motlagh SAO, Diffenderfer ES, Assenmacher CA, Bicher S, Atoche SJ, Ben-Josef E, Young RM, June CH, Koumenis C.: Proton radiation boosts the efficacy of mesothelin-targeting chimeric antigen receptor T cell therapy in pancreatic cancer. Proc Natl Acad Sci U S A 121: e2403002121, Jul 2024.
.Chowdhury P, Velalopoulou A, Verginadis II, Morcos G, Loo PE, Kim MM, Motlagh SAO, Shoniyozov K, Diffenderfer ES, Ocampo EA, Putt M, Assenmacher CA, Radaelli E, Lu J, Qin L, Liu H, Leli NM, Girdhani S, Denef N, Vander Stappen F, Cengel KA, Busch TM, Metz JM, Dong L, Lin A, Koumenis C.: Proton FLASH radiotherapy ameliorates radiation-induced salivary gland dysfunction and oral mucositis and increases survival in a mouse model of head and neck cancer. Mol Cancer Ther APR 2024.
Leli NM, Koumenis C. : A Novel Ubiquitin Complex Regulates Aneuploid Epithelial Tumors by Moderating an Integrated Stress Response Cancer Discov 1(13), March 2023.
Verginadis II, Avgousti H, Monslow J, Skoufos G, Chinga F, Kim K, Leli NM, Karagounis IV, Bell BI, Velalopoulou A, Salinas CS, Wu VS, Li Y, Ye J, Scott DA, Osterman AL, Sengupta A, Weljie A, Huang M, Zhang D, Fan Y, Radaelli E, Tobias JW, Rambow F, Karras P, Marine JC, Xu X, Hatzigeorgiou AG, Ryeom S, Diehl JA, Fuchs SY, Puré E, Koumenis C. : . A stromal Integrated Stress Response activates perivascular cancer-associated fibroblasts to drive angiogenesis and tumour progression. Nat Cell Biol. 24(6): 940-953, June 2022.
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.