Quantification of Mutational Processes and Phenotypic Switches
We aim to quantify mutational processes and phenotypic transitions in mammalian cells and cancer model systems, combining experimental evolution and mathematical modeling. To this end, we develop quantitative frameworks inspired by the Luria-Delbrück fluctuation assay to quantify the phenotypic switch to the persister phenotype and mutation rates in cancer cells exposed to growth-inhibitory targeted therapies. Our work also includes inference methods to quantify genomic mutation rates using sequencing data from controlled experimental setups. Furthermore, we are advancing computational methods to evaluate the potential effects of natural selection in shaping the phenotypes arising during a Mutation Accumulation experiment carried out in single-celled organisms.
Working on this topic: Simone Pompei, Mattia Corigliano, Valentina Guarino
Key publications:
M Russo, S Pompei, A Sogari, M Corigliano, G Crisafulli, A Puliafito, S Lamba, J Erriquez, A Bertotti, M Gherardi, F Di Nicolantonio, A Bardelli, M Cosentino Lagomarsino. A modified fluctuation-test framework characterizes the population dynamics and mutation rate of colorectal cancer persister cells. Nat Genet 54(7):976-984 2022
M Russo, G Crisafulli, A Sogari, NM Reilly, S Arena, S Lamba, A Bartolini, V Amodio, A Magrì, L Novara, I Sarotto, ZD Nagel, CG Piett, A Amatu, A Sartore-Bianchi, S Siena, A Bertotti, L Trusolino, M Corigliano, M Gherardi, M Cosentino Lagomarsino, F Di Nicolantonio, A Bardelli. Adaptive mutability of colorectal cancers in response to targeted therapies. Science 366 6472, 1473-1480 2019