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John Colicelli, Ph.D.

Work Email Address:
colicelli@mednet.ucla.edu

Laboratory Address:
Laboratory
BSRB 34610

UNITED STATES

Mailing Address:
Department
173717 mail code
615 Charles E. Young Drive
Los Angeles, CA 90095
UNITED STATES

Work Address:
Office
BSRB 350C

UNITED STATES

Lab Number:
(310) 206-1400
Office Phone Number:
(310) 825-1251



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Department / Division Affiliations
Co-Director, Howard Hughes Undergraduate Research Program
Professor and Vice Chair, Biological Chemistry
Member, ACCESS Program: Dept. of Biological Chemistry, Access Biochemistry, Biophysics, Structural Biology Home Area, Access Cell and Developmental Biology Home Area, Brain Research Institute, JCCC Signal Transduction and Therapeutics Program Area, Training Grants in Cellular and Molecular Biology, Genetics, Tumor Cell Biology

Research Interest:

Signal Transduction in Cancer and Neurobiology

<p>The research program in my laboratory is focused on the characterization of mammalian signal transduction pathways that control cell behavior and fate. 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 signaling in normal and transformed cells. There is a particular focus on RIN1, a downstream RAS effector protein. RIN1 interacts with and stimulates ABL family tyrosine kinases, which regulate actin remodeling, and RAB5 proteins, which regulate endocytosis.</P> <p> RIN1 binds specifically to activated RAS, a common oncoprotein. But RIN1 overexpression inhibits transformation of fibroblast and epithelial cells. This could result from a competitive block of other RAS effector pathways or activation of anti-tumor pathways, or both. We are investigating the specific role of RIN1 as a suppressor of breast tumor initiation and progression. We are also examining the role of RIN1 in leukemias and lymphomas, which often involve increased ABL activity.</P> <p> RIN1 is expressed at highest levels in mature forebrain neurons. Disruption of the RIN1 gene results in elevated long term potentiation and enhanced aversive memories in mutant mice. We are investigating the function of RIN1 as a negative modulator of neuronal plasticity and memory.</P> <p> Recent studies suggest that RIN2 and RIN3, two genes closely related to RIN1, have related but distinct signaling functions.</p>

Bio:

John Colicelli is a cell biologist and biochemist. He joined the Department of Biological Chemistry in the UCLA School of Medicine in 1990. He became a full professor in 2003. Dr. Colicelli earned his B.A. in Chemistry at Rutgers University and his M.S. and Ph.D. in Biochemistry from Columbia University in New York. He was a postdoctoral fellow at Cold Spring Harbor Laboratory. Dr. Colicelli's research is focused on molecular signal transduction in cancer biology and neuronal plasticity. He teaches cell biology at the graduate and undergraduate levels. Dr. Colicelli serves as a Departmental Vice Chair and as a member of the School of Medicine Faculty Executive Committee.

Publications:

Balaji K, Mooser C, Janson CM, Bliss JM, Hojjat H, Colicelli J. RIN1 Orchestrates the Activation of RAB5 GTPases and ABL Tyrosine Kinases to Determine EGFR Fate. J. Cell Sci 2012; (in press): .
Janson, C.M., Kasahara, N., Prendergast, G.C. and Colicelli, J. RIN3 Is a Negative Regulator of Mast Cell Responses to SCF. PLoS ONE 2012; (in press): .
M. Thai, P.Y. Ting, J. McLaughlin, D. Cheng, M. Müschen, O.N. Witte and J. Colicelli ABL Fusion Oncogene Transformation and Inhibitor Sensitivity Are Mediated by the Cellular Regulator RIN1. Leukemia 2011; 25(2): 290-300.
Colicelli John ABL tyrosine kinases: evolution of function, regulation, and specificity. Science signaling. 2010; 3(139): re6.
Cao, X. Tanis, K.Q. Koleske, A.J. Colicelli, J. Enhancement of ABL Kinase Catalytic Efficiency by a Direct Binding Regulator is Independent of Other Regulatory Mechanisms. Journal of Biological Chemistry. 2008; 283: 31401-31407.
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.
Wang Y, Colicelli J RAS interaction with effector target RIN1. Methods in enzymology. . 2001; 332: 139-51.
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.
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.
Balaji Kavitha, Mooser Chelsea, Janson Christine M, Bliss Joanne M, Hojjat Houmehr, Colicelli John RIN1 orchestrates the activation of RAB5 GTPases and ABL tyrosine kinases to determine the fate of EGFR. Journal of cell science. 2012; 125(Pt 23): 5887-96.
Janson Christine, Kasahara Noriyuki, Prendergast George C, Colicelli John RIN3 is a negative regulator of mast cell responses to SCF. PloS one. 2012; 7(11): e49615.
John Colicelli ABL Tyrosine Kinases: Evolution of Function, Regulation and Specificity. Science Signaling 2010; 3: re5.
Colicelli John Signal transduction: RABGEF1 fingers RAS for ubiquitination. Current biology : CB. 2010; 20(15): R630-2.
Joanne M. Bliss, Erin E. Gray, Ajay Dhaka, Thomas J. O'Dell and John Colicelli Fear learning and extinction are linked to neuronal plasticity through Rin1 signaling. Journal of Neuroscience Research. 2010; 88(4): 917-26.
Dzudzor Bartholomew, Huynh Lucia, Thai Minh, Bliss Joanne M, Nagaoka Yoshiko, Wang Ying, Ch'ng Toh Hean, Jiang Meisheng, Martin Kelsey C, Colicelli John Regulated expression of the Ras effector Rin1 in forebrain neurons. Molecular and Cellular Neurosciences. 2010; 43(1): 108-16.
Cao Xiaoqing, Tanis Keith Q, Koleske Anthony J, Colicelli John Enhancement of ABL kinase catalytic efficiency by a direct binding regulator is independent of other regulatory mechanisms. The Journal of biological chemistry. 2008; 283(46): 31401-7.
Deininger Katrin, Eder Matthias, Kramer Edgar R, Zieglgänsberger Walter, Dodt Hans-Ulrich, Dornmair Klaus, Colicelli John, Klein Rüdiger The Rab5 guanylate exchange factor Rin1 regulates endocytosis of the EphA4 receptor in mature excitatory neurons. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105(34): 12539-44.
Milstein Marc, Mooser Chelsea K, Hu Hailiang, Fejzo Marlena, Slamon Dennis, Goodglick Lee, Dry Sarah, Colicelli John RIN1 is a breast tumor suppressor gene. Cancer research. 2007; 67(24): 11510-6.
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.
Hu Hailiang, Bliss Joanne M, Wang Ying, Colicelli John 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.
Dhaka Ajay, Costa Rui M, Hu Hailiang, Irvin Dwain K, Patel Apoor, Kornblum Harley I, Silva Alcino J, O'Dell Thomas J, Colicelli John 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 Ying, Waldron Richard T, Dhaka Ajay, Patel Apoor, Riley Maggie M, Rozengurt Enrique, Colicelli John 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, 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.
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.
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, 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.