The lab focuses on understanding cell signaling, morphology, trafficking, and effector function of immune cells and tumour cells. We focus on the small GTPase Rap1 which has been shown to regulate many of these biological processes. Our latest work focuses on the the interplay between receptor signaling and cytoskeletal dynamics.
- The role of the Rap GTPases in controlling the trafficking and activation of B-lymphocytes
- Regulation and function of marginal zone B cells
- The role of the Rap GTPases in tumor cell motility and tumour metastasis
(Collaborative project with Dr. Cal Roskelley)
- Durand, C.A., M. Richer, K. Brenker, M. Graves, I. Shanina, K. Choi, M.S. Horwitz, K.D. Puri, and M.R. Gold (2013) Selective pharmacological inhibition of phosphoinositide 3-Kinase p110delta opposes the progression of autoimmune diabetes in non-obese diabetic (NOD) mice, Autoimmunity 46: 62-73.
- Tse, K.W.K., K.B.L. Lin, M. Dang-Lawson, A. Guzman-Perez, G.E. Aspnes, L. Buckbinder, and M.R. Gold, Small molecule inhibitors of the Pyk2 and FAK kinases modulate chemoattractant-induced migration, adhesion and Akt activation in follicular and marginal zone B cells (2012) Cell. Immunol. 275: 47-54.
- Freeman, S.A., V. Lei, M. Dang-Lawson, K. Mizuno, C.D. Roskelley, and M.R. Gold (2011) Cofilin-mediated F-actin severing is regulated by the Rap GTPase and controls the cytoskeletal dynamics that drive lymphocyte spreading and BCR microcluster formation, J. Immunol. 187: 5887-5900. Reviewed in J. Immunol. “In this Issue” 187: 5471, 2011.
- Freeman SA, McLeod SJ, Dukowski J, Austin P, Lee CCY, Miller-Martin B, Kubes P, McCafferty DM, Gold MR, Roskelley CD (2010) Preventing the activation or cycling of the Rap1 GTPase alters adhesion and cytoskeletal dynamics and blocks metastatic melanoma cell extravasation into the lungs. Cancer Research. 2010 Jun 1;70(11):4590-601.
- Lin KB, Tan P, Freeman SA, Lam M, McNagny KM, Gold MR. (2010) The Rap GTPases regulate the migration, invasiveness and in vivo dissemination of B-cell lymphomas. Oncogene. 2010 Jan 28;29(4):608-15.
- Durand CA, Hartvigsen K, Fogelstrand L, Kim S, Iritani S, Vanhaesebroeck B, Witztum JL, Puri KD, Gold MR. (2009) Phosphoinositide 3-kinase p110 delta regulates natural antibody production, marginal zone and B-1 B cell function, and autoantibody responses. J Immunol. 2009 Nov 1;183(9):5673-84.
- Tse KW, Dang-Lawson M, Lee RL, Vong D, Bulic A, Buckbinder L, Gold MR.(2009) B cell receptor-induced phosphorylation of Pyk2 and focal adhesion kinase involves integrins and the Rap GTPases and is required for B cell spreading. J Biol Chem. 2009 Aug 21;284(34):22865-77.
- Lin, K.B.L., S.A. Freeman, S. Zabetian, H. Brugger, M. Weber, V. Lei, M. Dang-Lawson, K.W.K. Tse, R. Santamaria, F.D. Batista, and M.R. Gold (2008) The Rap GTPases regulate B cell morphology, immune synapse formation, and signaling by particulate B cell ligands, Immunity 28: 75-87. Cover photo. Reviewed in Nature Rev. Immunol. 8: 168, 2008.
- Lee, R.L., J. Westendorf, and M.R. Gold (2007) Differential role of reactive oxygen species in the activation of mitogen-activated proteins kinases and Akt by CD40, the B cell antigen receptor, and CXCR4, J. Cell Commun. Signaling 1: 33-43.
- Durand, C.A., J.Westendorf, K.W.K. Tse, and M.R. Gold (2006) The Rap GTPases mediate CXCL13- and sphingosine 1-phosphate-induced chemotaxis, adhesion, and Pyk2 tyrosine phosphorylation in B-lymphocytes, Eur. J. Immunol. 36:2235-2249.
- McLeod, S.J., A.J. Shum, R.L. Lee, F. Takei, and M.R. Gold (2004) The Rap GTPases regulate integrin-mediated adhesion, cell spreading, actin polymerization, and Pyk2 tyrosine phosphorylation in B lymphocytes, J. Biol. Chem. 279: 12009-12019.
- Christian, S.L., R.L. Lee, S.J. McLeod, A.E. Burgess, A.H.Y. Li, M. Dang-Lawson, K.B.L. Lin, and M.R. Gold (2003) Activation of the Rap GTPases in B lymphocytes modulates B cell antigen receptor-induced activation of Akt but has no effect on MAP kinase activation, J. Biol. Chem. 278: 41756-41767.
- McLeod, S.J., A. H.Y. Li, R.L. Lee, A.E. Burgess, and M.R. Gold (2002) The Rap GTPases regulate B cell migration towards the chemokine SDF-1 (CXCL12). Potential role for Rap2 in promoting B cell migration, J. Immunol. 169: 1365-1371.
- Christian, S.L, P.V. Sims, and M.R. Gold (2002) The B cell antigen receptor regulates the transcriptional activator b-catenin via protein kinase C-mediated inhibition of glycogen synthase-3, J. Immunol. 169: 758-769.
- Ting, H.C., S.L. Christian, A.E. Burgess, and M.R. Gold (2002) Activation and phosphatidylinositol 3-kinase-dependent phosphorylation of protein kinase C-epsilon by the B cell antigen receptor, Immunology Lett. 82: 205-215.
- Zhu, N., L.M. Ramirez, R.L. Lee, N.S. Magnuson, G.A. Bishop, and M.R. Gold (2002) CD40 signaling in B cells regulates the expression of the Pim-1 kinase via the NF-B pathway, J. Immunol. 168: 744-754.
- Lin KB, Freeman SA, Gold MR. (2010) Rap GTPase-mediated adhesion and migration: A target for limiting the dissemination of B-cell lymphomas? Cell Adhesion and Migration 2010 Jul 4;4(3).
- Gold, M.R. (2008) B cell development: Important work for ERK, Immunity 28: 488-490.
- Gold, M.R. (2006) AKTion on mantle cell lymphoma, Blood 108: 1425-1426.
- Gold, M.R. (2003) Akt is TCL-ish: implications for B-cell lymphoma, Trends in Immunology 24: 104-108.
- Gold, M.R. (2002) To make antibodies or not: Signaling by the B cell antigen receptor, Trends in Pharmacological Sciences, 23: 316-324.