"Oncogenic Roles of Cellular Heterogeneity Inferred from Gene Expression Control"
Recent studies suggest that cellular heterogeneity promotes cancer progression and resistance to chemotherapy. However, prior studies indicate that cellular heterogeneity can also weaken drug resistance. Overall, the role of nongenetic mammalian cell heterogeneity (noise) in oncogenic processes is unclear. Examining the such effects of noise requires quantitative, mean-decoupled noise control, which was only recently established for mammalian cells. We developed mammalian synthetic gene circuits to decouple noise from the mean of Puromycin resistance gene expression in Chinese Hamster Ovary (Flp-In™-CHO) cells. In low Puromycin concentrations, the high-noise gene circuit delayed long-term adaptation, whereas it facilitated adaptation in high Puromycin. Therefore, cellular heterogeneity promotes or hinders the evolution of drug resistance, depending on the level of stress. Using a new platform for gene circuit integration, we are currently working to discover how metastasis-related phenotypes depend on specific protein-level distributions that we impose into various cancer cell lines.
Register in advance for this meeting
About the Speaker
Gábor Balázsi received his undergraduate Physics degree at the Babeş-Bolyai University in 1996 in Cluj/Kolozsvár, Romania. In 2001 he completed a Physics PhD in noise-induced spatiotemporal dynamics at the University of Missouri at Saint Louis. From 2002 - 2005, as a Systems Biology postdoctoral fellow at Northwestern University in Chicago, he studied gene-regulatory network response to environmental perturbations. From 2005 - 2006, as a Synthetic Biology postdoctoral fellow at the Center for Biodynamics at Boston University he developed synthetic gene circuits to study how cellular diversity promotes drug resistance. As Assistant and then Associate Professor at the University of Texas MD Anderson Cancer Center, from 2006 – 2014, with his team he built a growing library of expression-controlling synthetic gene circuits in yeast and human cells. He was a recipient of the 2009 NIH Director’s New Innovator Award, which aims to “stimulate highly innovative research and support promising new investigators”. Since 2014 and 2020, as the Henry Laufer Associate Professor and then Professor of Physical and Quantitative Biology at Stony Brook University, with his laboratory he has developed and has evolved synthetic gene circuits, advancing the understanding of gene network evolution, drug resistance and cancer progression. His research is part-experimental and part-computational, fostering interdisciplinary training while advancing the frontiers of quantitative biology.
