Dr. Altschuler's laboratory studies mechanisms of signal transduction by the second messenger cAMP in cell proliferation. cAMP-dependent protein kinase (PKA) and Exchange protein activated by cAMP (Epac) represent the main effectors of cAMP action. Both pathways converge at the level of the small GTPase Rap1b, via its Epac-mediated activation and PKA-mediated phosphorylation. The role of Rap1 activation (Epac) and phosphorylation (PKA) coordinating the early rate-limiting events in cAMP-dependent cell proliferation are studied using a multidisciplinary approach including molecular and cellular biology techniques in vitro, as well as in vivo validation using transgenic/knock in technologies in endocrine tumor models.
The research in the laboratory of Dr. Fernandez focuses on the pharmacogenomics of adverse drug reactions. The immunogenicity of protein-based therapeutics is a major problem that can lead to life-threatening complications and reduce or eliminate the therapeutic effects of biologics. The objectives of Dr. Fernandez’s research are to elucidate the mechanism of adverse drug reaction by identifying polymorphisms (variations) in genes that can explain why certain patients are predisposed to developing immune responses to biologics, to identify therapeutic strategies that can block and maintain therapeutic drug concentrations, and to develop clinical laboratory tests that can monitor drug bioavailability and immunogenicity to indicate when a drug substitution is appropriate. Dr. Fernandez has extensively studied the immune response to the chemotherapeutic agent, asparaginase, which is an essential component of pediatric acute lymphoblastic leukemia (ALL) therapy.
Dr. Edward Chu is involved in basic, clinical, and translational cancer research. His basic research interests are focused on the characterization of molecular mechanisms underlying the development of cellular drug resistance, especially as it relates to the fluoropyrimidine class of anticancer agents. His research group was the first to identify translational autoregulation as a novel regulatory mechanism in eukaryotes for controlling the expression of the folate-dependent enzymes, thymidylate synthase and dihydrofolate reductase. His clinical/translational research efforts focus on identifying novel drugs and treatment strategies for colorectal cancer and other GI cancers and in developing early phase clinical trials. He has a strong interest in integrating Chinese herbal medicine with standard cancer chemotherapy, with the goal of enhancing clinical activity and reducing toxicities.