B.S., Universidad Nacional de Mar del Plata, Argentina, 1995
PhD, University of Alabama at Birmingham, 2002
Postdoc, UNC Chapel Hill
The research in our lab is centered in understanding the mechanisms of regulation of Rho family of small GTPases. Rho GTPases control many 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. Our lab is particularly interested in the role of Rho GTPases during cell adhesion, migration and cell invasion in both normal and cancer cells. Deregulation in Rho GTPase signaling has been associated with all stages of cancer progression, including proliferation, invasion and metastasis.
In breast cancer patients, the migration of cancer cells away from the primary tumor and their subsequent metastasis to distant organs is the leading cause of mortality. Cancer cells invade other tissues and enter the bloodstream by forming actin-rich membrane protrusions called invadopodia that degrade the extracellular matrix (ECM). Formation of invadopodia involves a dramatic rearrangement of the actin cytoskeleton, a process that is regulated by the Rho family of GTPases. However, very little is known about the molecular mechanisms controlling Rho GTPases activation, or about the identity of their upstream regulators and downstream effectors during invadopodia formation.
CURRENT Laboratory grants
1R21CA194776-01A1, NIH/NCI (Garcia-Mata, PI) 05/12/2016-03/31/2018, "RhoG Signaling in Invadopodia"
1R15 CA199101-01A1 NIH/NCI (Garcia-Mata, PI) 05/01/2016-03/31/2019, "Regulation of Invadopodia formation by RhoG specific GEFs and GAPs"
1R03CA197227-01A1 NIH/NCI (Garcia-Mata, PI), 07/01/2016-6/30/2018, "A Novel RhoG Protein Interaction Network in Invadopodia"
Goicoechea S. M., Zinn A. , Awadia S., Snyder K., and Garcia-Mata R. 2017. A RhoG-mediated signaling pathway that modulates invadopodia formation in breast cancer cells, Journal of Cell Science: doi: 10.1242/jcs.195552
Diaphanous-Related Formin mDia2 and CXCL12 Chemokine Signaling Intersect to Drive Tumor Cell Amoeboid Transitions, M. M. Wyse, S.M. Goicoechea, R. Garcia-Mata, A. L. Nestor-Kalinoski, and K. M. Eisenmann, 2017, Biochem Biophys Res Commun. Jan 21. pii: S0006-291X(17)30136-5. doi: 10.1016/j.bbrc.2017.01.087. [Epub ahead of print]
Garcia-Mata R. 2014. Arrested Detachment: A DEPDC1B-mediated de-adhesion mitotic checkpoint. Dev. Cell 31 , 4 , 387-389.
Aguilar H, Urruticoechea A, Halonen P, Kiyotani K, Mushiroda T, Barril X, Serra-Musach J, Islam A, Caizzi L, Di Croce L, Nevedomskaya E, Zwart W, Bostner J, Karlsson E, Tenorio GP, Fornander T, Sgroi DC, Garcia-Mata R, Jansen MP, García N, Bonifaci N, Climent F, Soler MT, Rodríguez-Vida A, Gil M, Brunet J, Martrat G, Gómez-Baldó L, Extremera AI, Figueras A, Balart J, Clarke R, Burnstein KL, Carlson KE, Katzenellenbogen JA, Vizoso M, Esteller M, Villanueva A, Rodríguez-Peña AB, Bustelo XR, Nakamura Y, Zembutsu H, Stål O, Beijersbergen RL, Pujana MA. 2014. VAV3 mediates resistance to breast cancer endocrine therapy. Breast Cancer Res. May 28;16(3):R53.
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, Apr 2;8(4).
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 Apr;16(4):376-81.
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.
Sesma JI, Kreda SM, Steinckwich-Besancon N, Dang H, García-Mata R, Harden TK, Lazarowski ER. 2012. The UDP-sugar-sensing P2Y14 receptor promotes Rho-mediated signaling and chemotaxis in human neutrophils. Am J Physiol Cell Physiol. 303(5):C490-8.
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.
F. Waheed, P. Speight, Q. Dan, R. Garcia-Mata, K. Szaszi. Affinity precipitation of active Rho-GEFs using a GST-tagged mutant Rho protein (GST-RhoA(G17A)) from epithelial cell lysates. 2012 JoVE e3932.
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. Feb;26(2):469-79.
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.
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.
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 and R. Garcia-Mata. 2010. RhoGDI: A rheostat for the Rho switch. Small GTPses, 1, 65-68.
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. Nat Cell Biol. 12:477-483. (*equal contribution)
A.D. Dubash, M. Menold, T. Samson, E. Boulter, R. Garcia-Mata, R. Doughman, K. Burridge. 2009. Focal Adhesions: New angles on an old structure. International Reviews in Cell and Molecular Biology; 277:1-65.
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. 28: 587-598.
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. (* This manuscript has been awarded "paper of the year 2007" by J. Cell Sci. editors).
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. 119:3316-3324.
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. 406:425-437.
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. 6:374-385.
R. Garcia-Mata and E. Sztul. 2003. The membrane-tethering protein p115 interacts with GBF1, an ARF guanine-nucleotide-exchange factor. EMBO Rep. 4:320-325.
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. 14:2250-2261.
E. Brandon, Y. Gao, R. Garcia-Mata, C. Alvarez and E. Sztul. 2003. Membrane targeting of p115 phosphorylation mutants and their effects on Golgi integrity and secretory traffic. Eur J Cell Biol. 82:411-20.
C. Alvarez, R. Garcia-Mata, E. Brandon and E. Sztul. 2003. COPI recruitment is modulated by a Rab1b-dependent mechanism. Mol Biol Cell. 14:2116-127.
H. Ito, K. Kamei, I. Iwamoto, Y. Inaguma, R. Garcia-Mata, E. Sztul and K. Kato. 2002. Inhibition of proteasomes induces accumulation, phosphorylation, and recruitment of HSP27 and alphaB-crystallin to aggresomes. J Biochem (Tokyo). 131:593-603
R. Garcia-Mata, Y. S. Gao and E. Sztul. 2002. Hassles with taking out the garbage: aggravating aggresomes. Traffic. 3:388-396
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. 276:2693-2700
A. D. Linstedt, S. A. Jesch, A. Mehta, T. H. Lee, R. Garcia-Mata, D. S. Nelson and E. Sztul. 2000. Binding relationships of membrane tethering components. The giantin N terminus and the GM130 N terminus compete for binding to the p115 C terminus. J Biol Chem. 275:10196-10201
R. Garcia-Mata, Y. Gao, C. Alvarez and E. S. Sztul. 2000. The membrane transport factor p115 recycles only between homologous compartments in intact heterokaryons. Eur J Cell Biol. 79:229-239
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. 146:1239-1254
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. 143:319-331
R. Garcia-Mata, R. D. Conde and P. M. Sanllorenti. 1998. Contribution of breakdown in the regulation of mouse liver glutathione S-transferase subunits during protein depletion and re-feeding. Biochim Biophys Acta. 1448:46-50
R. Garcia-Mata, J. Capdevielle, J. C. Guillemot, P. Ferrara, R. D. Conde and P. M. Sanllorenti. 1997. Protein depletion and refeeding change the proportion of mouse liver glutathione S-transferase subunits. Biochim Biophys Acta. 1357:272-280