Professor of Pharmacology
Ph.D., University of California, San Diego
Key Words: proteases, G protein-coupled receptors, signal transduction, membrane trafficking, ubiquitination, inflammation, endothelial cells, breast cancer
The focus of our research is on protease signaling in vascular endothelial cells and breast cancer progression. Endothelial cells line blood vessels and form a semi-permeable barrier. Endothelial dysfunction contributes to many pathological conditions including cardiovascular disease, cancer and sepsis progression. During vascular inflammation and injury breakdown of the endothelial barrier occurs. We are examining how activation of GPCRs, specifically PARs, by distinct proteases differentially regulates endothelial barrier breakdown (pro-inflammatory signaling) versus cytoprotection (anti-inflammatory signaling) through selective activation of specific signaling pathways. The molecular mechanisms by which ubiquitin and subcellular compartmentalization mediate endothelial PAR signaling is being actively investigated. We also discovered that signaling by PAR1 is dysregulated in invasive breast cancer and consequently promotes tumor progression. We are examining how the endocytic machinery and the tumor suppressor ARRDC3 contribute to dysregulation of PAR1 trafficking and signaling to the Hippo pathway.
Selected Publications | PubMed Listing
U.J.K. Soh and J. Trejo. (2011) Activated protein C promotes protease-activated receptor-1 cytoprotective signaling through beta-arrestins and dishevelled-2 scaffolds. Proc. Natl. Acad. Sci. USA.108: E1372-E1380
M.R. Dores, B. Chen, H. Lin, U.J.K. Soh, M.M. Paing, W. A. Montagne, T. Meerloo and J. Trejo. (2012) ALIX binds a YPX3L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. J. Cell Biol. 197: 407-419
H. Lin and J. Trejo. (2013) Transactivation of the PAR1-PAR2 heterodimer by thrombin elicits beta-arrestin-mediated endosomal signaling. J. Biol. Chem. 288:11203-1121
M. R. Dores and J. Trejo. (2014) Atypical regulation of G protein-coupled receptor intracellular trafficking by ubiquitination. Curr. Opin. Cell Biol. 27: 44-50.
A.G. Soto, T.H. Smith, B. Chen, S. Bhattcharya, I. Canto Cordova, T. Kenakin, N. Vaidehi and J. Trejo. (2015) N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. Proc. Natl. Acad. Sci. USA 117:E3600-3608
N.J. Grimsey, B. Aguilar, T.H. Smith, P. Le, A.L. Soohoo, M.A. Puthenveedu, V. Nizet and J.Trejo. (2015) Ubiquitin plays an atypical role in GPCR-induced p38 MAP kinase activation on endosomes. Journal Cell Biology 210:1117-1131.