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Research Description:
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.
Education:
B.S. (Biology), University of Buenos Aires, Argentina, 1983. Ph.D. (Biology), University of Buenos Aires, Argentina, 1989. Postdoctoral Fellow, Department of Cell Biology, Duke University Medical Center, 1993-1999.
Important Publications:
- Zuo H, M Gandhi, MM Edreira, D Hochbaum, VL Nimgaonkar, P Zhang, J DiPaola, V Evdokimova, DL Altschuler and YE Nikiforov. Downregulation of Rap1GAP through promoter hypermethylation and loss of heterozygosity promotes invasion and progression of thyroid tumors. Cancer Research 70:1389-1397, 2010
- Edreira M, S Li, D Hochbaum, S Wong, AA Gorfe, F Ribeiro-Neto, VL Woods and DL Altschuler. Phosphorylation-induced conformational changes in Rap1b: Allosteric effects on switch domains and effector loop. J Biol Chem 284:27480-27486, 2009
- Hochbaum D, K Hong, G Barila, F Ribeiro-Neto and DL Altschuler. Epac, in synergy with PKA, is required for cAMP-mediated mitogenesis. J Biol Chem 283:4464-4468, 2008
- Hong K, L Lou, S Gupta, F Ribeiro-Neto and DL Altschuler. A novel Epac-Rap-PP2A signaling module controls cAMP-dependent Akt regulation. J Biol Chem 283:23129-23138, 2008
- Ribeiro-Neto F, A Leon, J Urbani-Brocard, L Lou, A Nyska and DL ltschuler. cAMP-dependent oncogenic action of Rap1b in the thyroid gland. J Biol Chem 279(45):46868-46875 , 2004
- Hochbaum D, T Tanos, F Ribeiro-Neto, D Altschuler and OA Coso. Activation of JNK by Epac is independent of its activity as a Rap guanine nucleotide exchanger. J Biol Chem 278(36):33738-33746 , 2003
- Lou L, J Urbani, F Ribeiro-Neto and DL Altschuler. cAMP inhibition of Akt is mediated by activated and phosphorylated Rap1b. J Biol Chem 277(36):32799-32806, 2002
- Ribeiro-Neto F, J Urbani, N Lemee, L Lou and DL Altschuler. On the mitogenic properties of Rap1b: cAMP-induced G(1)/S entry requires activated and phosphorylated Rap1b. Proc Natl Acad Sci USA 99:5418-5423, 2002
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