TITLE: “Cellular plasticity and fate choices in developing tissues and single cancer cells”
ABSTRACT: While cellular processes are often reproducible and precise, cells may also alter their molecular states and adopt new fates in response to stimuli, a phenomena referred to as “plasticity”. I am interested in understanding the control principles governing cellular plasticity and fate decisions in response to mutational and pharmacologic stresses in tissue development and cancer. I will first describe my work on quantitative approaches to monitor and control developmental signaling during fly embryogenesis. My findings reveal the complex and counterintuitive effects of pathogenic germline mutations in the highly conserved Ras signaling pathway on spatiotemporal patterning and morphogenesis. This work has implications for a large class of developmental abnormalities and our understanding of their origins and potential treatments. The second part of my talk is motivated by recent studies revealing how rare and transient non-genetic fluctuations in individual cancer cells enable them to survive pharmacologic stress, such as molecularly targeted therapies. Unlike the binary nature of Darwinian selection whereby mutations are either present or not, non-genetic fluctuations can exist on one, or even multiple continuums of variation. How this non-genetic variability maps to the eventual resistant fates upon drug exposure is an emerging paradigm of cellular plasticity. Integrating novel theoretical and experimental frameworks, I will present my findings on 1. Identifying the origins and nature of the unique transcriptional molecular states underlying this plasticity; and 2. Connecting these molecular states to their eventual drug-resistant fates by tracking thousands of uniquely barcoded cell lineages. Moving forward, my group will adapt these quantitative approaches and concepts to measure, model, and engineer plasticity and its roles in tissue development and disease.