Constantinos Koumenis, PhD

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.

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. : 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 effica