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03. November 2023
14:00 PM - 15:00 PM

Borschkegasse 8a
1090 Vienna

Lecture Hall

Alexis Lomakin

Medical University of Vienna
Institute for Pathobiochemistry & Genetics


How does 'form-follows-function' in therapy-induced cancer cell senescence?

Quantifiable changes in cell morphology are one of the most commonly used observable biomarkers of (pre-)cancerous lesions in epithelial tissues and organs. One noticeable morphological alteration is the stereotypic increase of the whole-cell size in tumor cells undergoing nuclear expansion due to polyploidization. Such enlarged cells are thought to experience senescence/aging associated with permanent cell cycle arrest and functional decline. This is why, entire generations of medical students and biology majors for decades were taught to ignore these cells in functional studies as they are the cells in the process of degeneration. For this reason, inducing senescent polyploid cancer cells was also considered a desired outcome during chemotherapeutic interventions. However, recent studies show that these cells can seed tumor relapse upon chemotherapy withdrawal, suggesting that senescent polyploid cancer cells are capable of evading classic senescence programs. The molecular and cellular mechanisms of this evasion remain unclear partly due to lack of knowledge about the fundamental biology of cancer cells in a therapy-induced senescence (TIS) state. In my talk, I will describe our current research program addressing whether TIS cancer cells scale the rate of metabolic reactions according to their size, and whether it is beneficial or detrimental when it comes to survival under stress.

About the speaker:
Alexis pursued his Ph.D. degree in Cell Biology and advanced Microscopy by participating in the NIH Fogarty International Collaboration Consortium Russia-Netherlands-USA, whose main goal was to study the effect of mitotic anticancer drugs on interphase cell functions (Lomakin et al. Developmental Cell, 2009). Obtaining a Leukemia & Lymphoma Society/LLS, USA Fellowship, he became a Postdoc at the Harvard Medical School Dana-Farber Cancer Cell Biology Program in Boston. There, he described a new type of regulation behind the epithelial-to-mesenchymal transition/EMT based on nongenetic mechanisms involving mechanochemical pathways controlling cell shape plasticity (Lomakin et al. Nature Cell Biology, 2015). Thanks to support from the Marie Skłodowska-Curie Fellowship Program and a King’s Fellowship Scheme, Alexis established his first independent lab at King's College London, UK with the objective to discover the physico-chemical mechanisms through which morphology can template signaling and metabolic functions of cancer cells (Lomakin et al. Science, 2020). He is currently a PI at the Center for Pathobiochemistry & Genetics, MedUni Wien, where his team combines quantitative microscopy and -omics approaches to decode the logic and exploit therapeutic vulnerabilities of cell size change in cancer & aging (Belhadj et al. Aging Cell, 2023).