B.S., Universidad Nacional de Mar del Plata, Argentina, 1995
PhD, University of Alabama at Birmingham, 2002
Postdoc, UNC Chapel Hill
Silvia Goicoechea, Research Assistant Professor
Alejandra Valdivia, PhD, Postdoctoral Fellow
The research in the lab is centered in understanding the mechanisms of regulation of Rho family of small GTPases. Rho GTPases control almost every aspects of cell behavior, such as the organization of the cytoskeleton, cell migration, cell–cell and cell–matrix adhesion, cell cycle progression, gene expression and cell polarity. These processes have been shown to play essential roles both in normal cell function, as well as in abnormal cell behavior, including metastasis, atherosclerosis, inflammation and hypertension.
Rho GTPases function as a link between surface receptors and the actin cytoskeleton. Rho proteins act as molecular switches by cycling between an active (GTP bound) and an inactive (GDP bound) state. The activation of Rho proteins is mediated by specific guanine-nucleotide exchange factors (GEFs), which catalyze the exchange of GDP for GTP. In their active state, GTPases interact with high affinity with one of several downstream effectors to modulate their activity and localization. The signal is terminated by hydrolysis of GTP to GDP a reaction that is stimulated by GTPase activating proteins (GAPs). In addition, guanine nucleotide dissociation inhibitors (GDIs) negatively regulate Rho GTPases by sequestering Rho proteins and interfering with both the GDP/GTP exchange and the GTP hydrolysis
Current projects in the lab address the role of GTPases in podosomes and invadopodia formation, the regulation of Rho-GEFs by scaffolding proteins, the mechanisms of regulation of RhoGDI and the function of RhoA in the nucleus.
- S.M. Goicoechea , S. Awadia and R. Garcia-Mata. 2014. I'm coming to GEF you. Regulation of RhoGEFs during cell migration. Cell Adhesion & Migration (in press)
- C. Guilluy, L. Osborne, L. Van Landeghem, L. Sharek, R. Superfine, R. Garcia-Mata, and Keith Burridge. 2014. Isolated nuclei adapt to force and reveal a mechanotransduction pathway within the nucleus, Nature Cell Biology (Mar 9. doi: 10.1038/ncb2927. [Epub ahead of print])
- S.M. Goicoechea , R. Garcia-Mata, J. Staub, A. Valdivia, L. Sharek, C.A. McCulloch, R. Hwang, R. Urrutia, J.J. Yeh, H.J, Kim, and C. Otey. 2014. Palladin promotes invasion of pancreatic cancer cells by enhancing invadopodia formation in cancer-associated fibroblasts, Oncogene (6;33(10):1265-73)
- Zhang X, Tao Y, Wang J, Garcia-Mata R, Markovic-Plese S. 2013. Simvastatin inhibits secretion of Th17-polarizing cytokines and antigen presentation by DCs in patients with relapsing remitting MS. Eur J Immunol. 43, 281-289.
- V. Krishna Subbaiah, P. Massimi, S. Shi Boon, M.P. Myers, L. Sharek, R. Garcia-Mata and L. Banks. 2012. The Invasive Capacity of HPV Transformed Cells Requires the hDlg-dependent enhancement of SGEF/RhoG Activity. PLoS Pathogens, 8(2):e1002543.
- V.A. Bankaitis, R. Garcia-Mata and C.J. Mousley. 2012. Golgi Membrane Dynamics and Lipid Metabolism. Current Biology, 22, R414-R424.
- E. Boulter and R. Garcia-Mata. 2012. Role of RhoGDI1 in the regulation of RhoGTPases. I. Methods in Molecular Biology,827:97-105.
- Boulter, E., Estrach, S., Garcia-Mata, R., and Feral, C., 2011. Off the beaten paths: alternative and crosstalk regulation of Rho GTPases. FASEB J. (Oct 28. Epub ahead of print).
- Roney KE, O'Connor BP, Wen H, Holl EK, Guthrie EH, Davis BK, Jones SW, Jha S, Sharek L, Garcia-Mata R, Bear JE, Ting JP. 2011. Plexin-b2 negatively regulates macrophage motility, rac, and cdc42 activation. PLoS One.;6(9): e24795.
- C. Guilluy, R. Garcia-Mata and K. Burridge. 2011. Rho protein crosstalk: another social network? Trends in Cell Biology 21, 718-726.
- C. Guilluy , A.D. Dubash, and R. Garcia-Mata. 2011. Analysis of RhoA and Rho GEF activity in whole cells and the cell nucleus. Nature Protocols 6, 2050-2060.
- R. Garcia-Mata, E. Boulter and K. Burridge. 2011. The Invisible Hand: Regulation of Rho GTPases by RhoGDIs. Nature Reviews in Molecular and Cell Biology.12:493-504 (featured on the cover).
- C. Guilluy , V. Swaminathan , R. Garcia-Mata, E. O'Brien III, R. Superfine, and K. Burridge. 2011. The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins. Nat Cell Biol 13:722-727. .
- A.D. Dubash, M. Srougy, C. Guilluy, E. Boulter , K. Burridge and R. Garcia-Mata. 2011. The Small GTPase RhoA Localizes to the Nucleus and is Activated by Net1 and DNA Damage Signals. PLoS one 6, e17380.
- E. Boulter*, R. Garcia-Mata*, C. Guilluy, A.D. Dubash, G. Rossi, P.J. Brennwald and K. Burridge.2010. Regulation of RhoGTPase crosstalk, degradation and activity by RhoGDI1. Nature Cell Biology, 12, 477-483 (*equal contribution).
- S. Goicoechea, H. Prentice-Dunn, B. Bednarski, R. Garcia-Mata, X. Ding, H.J. Kim, and C.A. Otey. 2009. Palladin Expression Contributes to Invasive Motility in Human Breast Cancer Cells. Oncogene. 2009;28: 587-98
- R. Garcia-Mata, A.D. Dubash, L. Sharek, H.S. Carr, J.A. Frost and K. Burridge. 2007. The nuclear RhoA-exchange factor Net1 interacts with proteins of the Dlg family, affects their localization and influences their tumor suppressor activity. Mol. Cell. Biol, 27: 8683-8697.
- A.D. Dubash, K. Wennerberg, R. García-Mata, M.M. Menold, W.T. Arthur, K. Burridge. 2007. A novel role for Lsc/p115 RhoGEF and LARG in regulating RhoA activity downstream of adhesion to fibronectin. J. Cell Sci. 120: 3989-3998.
- J. Van Buul, M. Allingham, T. Samson, J. Meller, E. Boulter, R. Garcia-Mata and K. Burridge. 2007. RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration. J. Cell Biol. 178: 1279-1293.
- R. Garcia-Mata and K. Burridge. 2007. Catching a GEF by its tail. Trends in Cell Biology. 17, 36-43.
- S. Goicoechea, D. Arneman, A. Disanza, R. Garcia-Mata, G. Scita and C. A. Otey. 2006. Palladin binds to Eps8 and enhances the formation of dorsal ruffles and podosomes in vascular smooth muscle cells. J Cell Sci. 119:3316-24
- R. Garcia-Mata, K. Wennerberg, W. T. Arthur, N. K. Noren, S. M. Ellerbroek and K. Burridge. 2006. Analysis of activated GAPs and GEFs in cell lysates. Methods Enzymol. 406:425-37
- T. Szul, R. Garcia-Mata, E. Brandon, S. Shestopal, C. Alvarez and E. Sztul. 2005. Dissection of membrane dynamics of the ARF-guanine nucleotide exchange factor GBF1. Traffic. 6:374-85
- R. Garcia-Mata and E. Sztul. 2003. The membrane-tethering protein p115 interacts with GBF1, an ARF guanine-nucleotide-exchange factor. EMBO Rep. 4:320-5
- R. Garcia-Mata, T. Szul, C. Alvarez and E. Sztul. 2003. ADP-ribosylation factor/COPI-dependent events at the endoplasmic reticulum-Golgi interface are regulated by the guanine nucleotide exchange factor GBF1. Mol Biol Cell. 14:2250-61
- C. Alvarez, R. Garcia-Mata, E. Brandon and E. Sztul. 2003. COPI recruitment is modulated by a Rab1b-dependent mechanism. Mol Biol Cell. 14:2116-27
- R. Garcia-Mata, Y. S. Gao and E. Sztul. 2002. Hassles with taking out the garbage: aggravating aggresomes. Traffic. 3:388-96
- C. Alvarez, R. Garcia-Mata, H. P. Hauri and E. Sztul. 2001. The p115-interactive proteins GM130 and giantin participate in endoplasmic reticulum-Golgi traffic. J Biol Chem. 276:2693-700
- R. Garcia-Mata, Z. Bebok, E. J. Sorscher and E. S. Sztul. 1999. Characterization and dynamics of aggresome formation by a cytosolic GFP-chimera. J Cell Biol. 146:1239-54
- D. S. Nelson, C. Alvarez, Y. S. Gao, R. Garcia-Mata, E. Fialkowski and E. Sztul. 1998. The membrane transport factor TAP/p115 cycles between the Golgi and earlier secretory compartments and contains distinct domains required for its localization and function. J Cell Biol. 143:319-31