; Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine
Oncoproteins are well-known drivers of cancer and participate in virtually all steps of oncogenic transformation. Among these, RAS oncoproteins are drivers of tumor initiation and progression and therapies targeting these directly or their downstream pathways have resulted in unprecedented clinical benefit in cancer. However, recent advances in genomic medicine have revealed that many of the known RAS oncoproteins and their regulators are also involved in the pathogenesis of a group of congenital disorders termed RASopathies. In these individuals, germline pathogenic variants give rise to phenotypes that can shed light on the physiological function of the proto-oncoprotein. Our laboratory’s research has been focused on understanding the role of RAS oncoproteins in both cancer and congenital disorders. During my talk I will discuss our recent efforts in characterizing a non-classical RAS GTPase termed RIT1, which is mutated in both cancer and RASopathies. We have identified a novel mechanism of regulation for this GTPase and have developed unique cellular and animal models to understand the role of RIT1 at the organismal level. Our work provides novel insights into the regulation, function, and pathogenesis of RAS oncoproteins.
Dr. Pau Castel is an Assistant Professor at the Department of Biochemistry and Molecular Pharmacology at the New York University School of Medicine. Dr. Castel performed his graduate work at Memorial Sloan Kettering Cancer Center under the supervision of Dr. José Baselga and undertook postdoctoral studies at the University of California San Francisco in the laboratory of Dr. Frank McCormick. His research is aimed at understanding the molecular mechanisms underlying oncoprotein transformation in cancer and congenital disorders, including RASopathies and the neurofibromatoses. His laboratory employs biochemical, signal transduction, and mouse genetics to study oncoproteins of the Ras-MAPK and PI3K pathways with the goal of developing rational-based therapies for these disorders.
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