How Targeted Therapies Exploit Signaling (src) and Metabolic (Glucose) Overdependencies in Cancer Homeostasis

Friday, May 17, 2013 - 2:00pm
Frederic de Hoffman Auditorium, Salk Institute for Biological Studies
Thomas Graeber, Ph.D.

Associate Professor, Molecular and Medical Pharmacology

University of California, Los Angeles

How Targeted Therapies Exploit Signaling (src) and Metabolic (Glucose) Overdependencies in Cancer Homeostasis

Abstract: 
Unbiased inquiries into signaling and metabolism using phospho-proteomics have repeatedly pointed us to networks involving negative and positive feedback, cross-talk, synergy, and unexpected results.  Examples include negative feedback of Src signaling in kinase inhibitor-resistant Bcr-Abl-driven leukemias (Rubbi et al.); feed-forward, synergistic amplification of signaling upon metabolic stress leading to catastrophic death (Graham et al.); synergistic co-treatments that can prevent kinase inhibitor resistance; and the identification of druggable tyrosine signaling in prostate cancer, a tumor type in which tyrosine signaling mutations are rare (Drake et al.). In sum, these examples provide illustrations of how the signaling and metabolic states of cancer cells, while homeostatic, can be relatively unstable to disruptive perturbations.
Bio: 
Dr. Graeber received his B.S. in Physics from UCLA and his Ph.D. in Physics/Cancer Biology from Stanford University with Amato Giaccia studying the role of p53 in hypoxia-induced apoptosis. He did postdoctoral fellowships in signal transduction with Ke Shuai (UCLA), and in bioinformatics and proteomics with David Eisenberg (UCLA) investigating oncogenic autocrine and kinase signaling. He is now faculty in the Department of Molecular and Medical Pharmacology at UCLA and a member of the Crump Institute for Molecular Imaging. He is an American Cancer Society Research Scholar.