- Ras superfamily GTPases, oncogenes, signal transduction, and target-based anti-cancer drug discovery
The broad goal of our research is to delineate the molecular basis for cancer. One major emphasis of our studies is the study of Ras oncoproteins, which are key regulators of signal transduction pathways that control normal cell growth and differentiation. Mutated Ras proteins are found in 30% of human cancers and promote cancer cell growth, invasion, and metastasis. We are evaluating how aberrant Ras proteins alter the regulation of cell cycle progression, programmed cell death, and gene expression to promote oncogen sxdsxdesis. One facet of these studies involves a dissection of the complex signaling mechanisms that are deregulated by Ras in cancer cells, including the Raf-MEK-ERK mitogen-activated protein kinase cascade. A long-term goal of these studies is to use this information for the development of anti-Ras drugs as novel approaches for cancer treatment (e.g., farnesyltransferase and kinase inhibitors). Another major aspect of our studies involves the study of Ras-related proteins. The human Ras proteins are but a small branch of a larger superfamily of Ras-related GTPases. While Ras proteins are mediators of positive growth regulation, Ras-related proteins control a range of diverse cellular processes that include actin cytoskeletal organization ( Rho proteins) and negative growth regulation (DBC2, Rerg, NOEY2). A major goal of our studies has been to determine whether the aberrant activities of Ras-related proteins also contribute to malignant transformation. In particular, we have focused on the study of Rho family small GTPases, regulators of actin cytoskeletal organization and gene expression, and mediators of tumor cell invasion and metastasis. We utilize human cell culture and mouse models, as well as genetic studies in C. elegans to study mechanisms of signal transduction. Our studies focus on the role of aberrant signaling in the development and growth of cancers of the breast, ovary, pancreas, colon, lung and skin.
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