UCLA Neuroscience Program Ph.D. Admissions Neuroscience Faculty UCLA and Beyond  



John Colicelli
Signal Transduction in Cancer and Neurobiology

Work Email Address:  colicelli@mednet.ucla.edu

Laboratory Address:
BSRB 34610
Mailing Address:
173717 mail code
Work Address:
BSRB 350C
Phone Numbers:
(310) 206-1400 Laboratory
(310) 825-1251 Office

Selected Publications:

Hu, H., Milstein, M., Bliss, J.M., Thai, M., Malhotra, G. and Colicelli, J. Integration of TGFb and RAS Signaling Silences a RAB5 GEF and Enhances Growth Factor-Directed Cell Migration. Molecular and Cellular Biology 2008; 28: 1573-1583.
Milstein, M., Mooser, C., Malhotra, G., Hu, H., Fejzo, M., Slamon, D., Dry, S., Goodglick, L. and Colicelli, J. RIN1 Is a Breast Tumor Suppressor Gene. Cancer Research 2007; 67: 11510-11516.
Bliss, J.M. Venkatesh, B. Colicelli, J. The RIN Family of RAS Effectors. Methods in Enzymology 2006; 407: 335-344.
Hu H, Bliss JM, Wang Y, Colicelli J RIN1 is an ABL tyrosine kinase activator and a regulator of epithelial-cell adhesion and migration.. Current biology : CB. . 2005; 15(9): 815-23.
Colicelli J Human RAS superfamily proteins and related GTPases.. Science's STKE [electronic resource] : signal transduction knowledge environment. . 2004; 2004(250): RE13.
Dhaka A, Costa RM, Hu H, Irvin DK, Patel A, Kornblum HI, Silva AJ, O'Dell TJ, Colicelli J The RAS effector RIN1 modulates the formation of aversive memories.. The Journal of neuroscience : the official journal of the Society for Neuroscience. . 2003; 23(3): 748-57.
Wang Y, Waldron RT, Dhaka A, Patel A, Riley MM, Rozengurt E, Colicelli J The RAS effector RIN1 directly competes with RAF and is regulated by 14-3-3 proteins.. Molecular and cellular biology. . 2002; 22(3): 916-26.
Wang Y, Colicelli J RAS interaction with effector target RIN1.. Methods in enzymology. . 2001; 332: 139-51.
Lim YM, Wong S, Lau G, Witte ON, Colicelli J BCR/ABL inhibition by an escort/phosphatase fusion protein.. Proceedings of the National Academy of Sciences of the United States of America. . 2000; 97(22): 12233-8.
Atienza JM, Suh M, Xenarios I, Landgraf R, Colicelli J Human ERK1 induces filamentous growth and cell wall remodeling pathways in Saccharomyces cerevisiae.. Journal of Biological Chemistry. . 2000; 275(27): 20638-46.
Atienza JM, Susanto D, Huang C, McCarty AS, Colicelli J Identification of inhibitor specificity determinants in a mammalian phosphodiesterase.. Journal of Biological Chemistry. . 1999; 274(8): 4839-47.
Han L, Wong D, Dhaka A, Afar D, White M, Xie W, Herschman H, Witte O, Colicelli J Protein binding and signaling properties of RIN1 suggest a unique effector function.. Proceedings of the National Academy of Sciences of the United States of America. . 1997; 94(10): 4954-9.
Afar DEH, Han L, McLaughlin J, Wong S, Dhaka A, Parmar K, Rosenberg N, Witte ON, Colicelli J Regulation of the Oncogenic Activity of BCR-ABL by a Tightly Bound Substrate Protein RIN1.. Immunity 1997; 6: 773-782.
Spain BH, Bowdish KS, Pacal AR, Staub SF, Koo D, Chang CY, Xie W, Colicelli J Two human cDNAs, including a homolog of Arabidopsis FUS6 (COP11), suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction in yeast and mammalian cells.. Molecular and cellular biology. . 1996; 16(12): 6698-706.
Spain BH, Koo D, Ramakrishnan M, Dzudzor B, Colicelli J Truncated forms of a novel yeast protein suppress the lethality of a G protein alpha subunit deficiency by interacting with the beta subunit.. Journal of Biological Chemistry. 1995; 270(43): 25435-44.
Han L, Colicelli J A human protein selected for interference with Ras function interacts directly with Ras and competes with Raf1.. Molecular and cellular biology. . 1995; 15(3): 1318-23.
Pillai R, Fluckiger Staub S, Colicelli J Mutational mapping of kinetic and pharmacological properties of a human cardiac cAMP phosphodieterase.. Journal of Biological Chemistry 1994; 269: 30676-30681.
Pillai R, Kytle K, Reyes A, Colicelli J Use of a yeast expression system for the isolation and analysis of drug-resistant mutants of a mammalian phosphodiesterase.. Proceedings of the National Academy of Sciences of the United States of America. . 1993; 90(24): 11970-4.
Research Interest:

The research program in my laboratory is focused on the characterization of mammalian signal transduction pathways that control mitosis and cell remodeling. Genetic disruptions of these same pathways can lead to altered cell function and pathologies such as cancer. Biochemical and genetic techniques are employed to analyze the role of RAS and ABL signaling in normal and transformed cells. There is a particular focus on RIN1, a protein that interacts with both RAS and ABL family proteins. RIN1 binds specifically to activated RAS, a common oncoprotein. This interaction is competitive with other RAS effectors that bind to the same location. RIN1 can inhibit RAS-mediated transformation of cells by blocking these other pathways. The RIN1 protein also has a domain that mediates interaction with the ABL protein, a tyrosine kinase that is mutationally activated in some human leukemias. The association of RIN1 with BCR/ABL (an oncogenic mutant form of ABL) leads to enhanced transformation in vitro and accelerated leukemogenesis in vivo. When the ABL-binding domain of RIN1 is fused to a tyrosine phosphatase, however, this interaction can be co-opted to block BCR/ABL-mediated transformation and leukemogenesis. This type of "escort/inhibitor" strategy may prove useful for intervention in multiple types of tumors. Our research has also demonstrated that RIN1 is expressed at highest levels in mature forebrain neurons. Disruption of the RIN1 gene results in elevated long term potentiation and enhanced learning in mutant mice. We are investigating the function of RIN1 as a negative modulator of neuronal plasticity.