Georgios Karras
Associate Professor
The University of Texas MD Anderson Cancer Center
Department of Genetics
A single mutation can increase disease risk hundred-fold. For example, mutations in DNA repair genes such as BRCA1 dramatically increase the rate at which new mutations accumulate, driving biological heterogeneity during tissue aging and cancer. Yet because most mutations are detrimental, it remains unclear how cells tolerate and even exploit high mutational burdens in tumors and populations.
My lab studies how cellular plasticity allows cells to minimize the cost of mutation under stress. We have shown that the molecular chaperone HSP90, a sentinel of protein homeostasis, can buffer deleterious mutations in human cells, permitting genetic variation to accumulate without immediate functional consequences. We also found that HSP90’s buffering capacity is finite and is challenged by proteotoxic stress arising from the tumor microenvironment, tissue aging, and external or metabolic exposures. When HSP90 function is compromised, hidden mutations are revealed and become accessible to natural selection, leading to increased heterogeneity and accelerated evolution.
Using clinically relevant and unconventional model systems and single-cell spatial methods, we study how proteostasis, mutation, and stress interact in space and time to shape tumor progression, therapy resistance, and aging.
Rotation students in my lab gain exposure to a range of experimental approaches, including single-cell DNA sequencing, cell competition assays, and genome editing, while developing training in evolutionary biology, metabolism, and gene-environment interaction.
Education & Training
Ph.D., Ludwig Maximilian University of Munich, 2010
Research Info
Protein Homeostasis and Cancer Evolution