Wed@Hariri/Meet Our Fellows: Kirill Korolev

The Tug of War between Beneficial and Deleterious Mutations in Cancer

Abstract: The conventional view is that only a handful of mutations are needed for cancer progression, yet tumor genomes carry thousands of genetic changes. I will present a combination of theory, computation, and data analysis suggesting that most cancer mutations are damaging to the tumor. Cancer progression is then akin a tug-of-war between a few strong mutations that promote cancers and many weak mutations that hold it back. I will present a stochastic model of this competition and show that majority of genetic lesions fail to become clinical cancers. This model explained several paradoxical observations and allowed us to estimate the fitness cost of passenger mutations using large genomics and clinical data sets. The load of damaging mutations presents a possible target for anticancer therapy, but taking advantage of this load may be nontrivial. Our analysis shows that the outcome of tumorigenesis is non-monotonic in many parameters that control cancer evolution and a successful intervention requires an accurate computational model for tumor evolution. Finally, I will present our simulations of human evolution to suppress cancer and explain why some cancers occur only after a million of stem cell divisions while trillions of cell divisions are required to create a successful tumor in other tissues.

Bio: Kirill Korolev was selected as an Institute Junior Faculty Fellow in fall 2015. He is an assistant professor in the Department of Physics and Graduate Program in Bioinformatics at BU, which he joined in 2013. After receiving his PhD in theoretical physics from Harvard University in 2010, he spent three years at the Massachusetts Institute of Technology as a Pappalardo Postdoctoral Fellow. Professor Korolev uses mathematical modeling, computation, and statistical analysis of data to understand evolution and population dynamics in a variety of practical contexts. The main focus of his group is on the spatial organization of microbial colonies, evolution in cancer tumors, and invasions of exotic species or pests. He is also interested in sudden transitions in complex system such as an onset of dysbiosis in the gut microbiome. Overall, his work seeks simplicity in the complexity of dynamic and evolving collectives.