Systems Biology Analysis of Signaling in Cancer: Extension to ER Cross-talk

Abstract: Systems biology studies develop quantitative, predictive models of biological processes – typically using large data sets and a variety of mathematical and computational tools. Recent studies of the cancer genome have shown that tumors are enriched for coordinated mutations in pathways that regulate key functions such as the cell cycle. My lab seeks to understand the impact of these altered pathways on the cellular signaling network and cell phenotype, using a variety of experimental and mathematical techniques. In this talk, I will discuss recent work examining mutated K-RAS or N-RAS, GTPases that lay in the center of a variety of signaling cascades within the cell. Although K-RAS and N-RAS have similar biochemical activities, it has been demonstrated that K-RAS mutations, much more than N-RAS mutations, sensitize cells to apoptosis following treatment with the inflammatory cytokine, TNFα. Our results indicate that the different RAS mutants affect both positive feedback loops such as autocrine signals and negative feedback mechanisms including phosphatases. These studies may help improve our understanding of how oncogenic mutations alter the inflammatory response to promote tumor growth. I will also discuss ongoing studies in the lab to use these approaches to address priorities in women’s health, including breast and ovarian cancer.

Additional CS events.