JoAnn Trejo, Ph.D.
Professor of Pharmacology Assistant Vice Chancellor for Health Sciences Faculty Affairs
JoAnn Trejo, Ph.D.
Professor of Pharmacology
Assistant Vice Chancellor for Health Sciences Faculty Affairs
Research Interests
Our research is focused on cell signaling and how it controls vascular inflammation and cancer. We study the function of G protein-coupled receptors, specifically protease-activated receptors, the tumor suppressor alpha-arrestin ARRDC3 and ubiquitin-driven inflammatory signaling. We discovered that ubiquitination of a subset of GPCRs initiates p38 inflammatory signaling and endothelial dysfunction. A major challenge is to understand how this pathway is regulated. We also discovered a new GPCR lysosomal sorting pathway that is regulated by the adaptor proteins ALIX and alpha-arrestin ARRDC3 – this pathway is dysregulated in invasive cancer. Another challenge is to understand how and why GPCRs sort into the ALIX and ARRDC3- dependent lysosomal sorting pathway and the impact of the tumor suppressor ARRDC3 on GPCR signaling and cancer progression.
Selected Publications
Molinar-Inglis, C. A. Birch, D. A. Nicholas, L. Orduña-Castillo M. Cisneros-Aguirre, A. Patwardhan, B. Chen,J. Grimsey, L. J. Coronel, H. Lin, P.K.G. Menzies, M. A. Lawson, H. H. Patel and J. Trejo (2021). aPC/PAR1confers endothelial anti-apoptotic activity via a discrete β-arrestin-2-mediated Sphk1-S1PR1-Akt signaling axis.Proc. Natl. Acad. Sci. USA. Dec 7, 118(49):e2106623118, DOI: 10.1073/pnas.2106623118C.R. Rada, H. Mejia-Pena, N.J. Grimsey, I.C. Cordova, J. Olson, J. Wozniak, D. J. Gonzalez, V. Nizet and J. Trejo (2021). Heat shock protein 27 activity is linked to endothelial barrier recovery after proinflammatory GPCR- induced disruption. Sci. Signaling. Aug 31;14(698):eabc1044.
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. J. Cell Biol. 210:1117-1131
N. J. Grimsey, R. Narala, C. C. Rada, S. Mehta, B.S. Stephens, I. Kufareva, J. Lapek, D. J. Gonzalez, T.M. Handel, J. Zhang and J. Trejo (2018). A tyrosine switch on NEDD4-2 E3 ligase transmits GPCR inflammatory signaling. Cell Reports, 18:24(12):3312-3323
Y. Lin, J. M. Wozniak, N. J. Grimsey, S. Girada, A. Patwardhan, O. Molinar-Inglis, T.H. Smith, J.D. Lapek, D. J. Gonzalez and J. Trejo (2020). Phospho-proteomic analysis of protease-activated receptor-1 biased signaling reveals unique modulators of endothelial barrier function. Proc. Natl. Acad. Sci. USA, Mar 3;117(9):5039-5048.
Patwardhan, N. Cheng and J. Trejo (2021). Post-Translational Modifications of G Protein-Coupled Receptors Control Cellular Signaling Dynamics in Space and Time. Pharm. Rev. Jan;73(1):120-151.
A.K.S. Arakaki, W.-A. Pan, H. Wedegaertner, I. Roca-Mercado, L. Chinn, T. S. Gujral and J. Trejo (2021). Alpha-arrestin ARRDC3 tumor suppressor function is linked to GPCR-induced TAZ activation and breast cancer metastasis. J. Cell Sci. 134(8):jcs254888