Faculty

JoAnn Trejo

Associate Professor

Ph.D., Physiology and Pharmacology
University of California, San Diego

Curriculum Vitae [.pdf]

Research Interests:

  • Signaling: Characterization of GPCR-G protein coupling and -effector signaling
  • Protein trafficking: GPCR endocytosis and sorting to endosomes and lysosomes
  • Cancer: GPCR function in breast cancer tumorigenesis, invasion and metastasis

Research Synopsis:

Our laboratory is interested in the regulatory mechanisms that control signal transduction by G protein-coupled receptors (GPCRs). The heptahelical GPCRs belong to the largest family of cell surface signaling receptors encoded in the human genome. GPCRs signal to diverse extracellular stimuli and control vast physiological responses and are the targets of nearly half the drugs currently in use for the treatment of a variety of human diseases.

The focus of our work is on protease-activated receptors (PARs), which are GPCRs that signal in response to extracellular proteases.  PARs play crucial roles in hemostasis and thrombosis, as well as in inflammatory and proliferative responses triggered by vascular injury. PARs are also important for vascular development and have been implicated in tumor progression (see Figure). PARs are activated by a unique irreversible proteolytic mechanism and therefore signaling must be tightly regulated.  Desensitization and trafficking of proteolytically activated PARs control the magnitude, duration and spatial aspects of receptor signaling. We have identified and study novel modes of PAR endocytic sorting and signal regulation in endothelial and fibroblast cell model systems. We are currently performing siRNA library screens of ubiquitin modifying enzymes and regulators of GPCR signaling to identify new molecules and modes of signal regulation.

Our laboratory also studies PAR function in breast cancer progression. PARs are overexpressed in several types of malignant cancer, transmit signals in response to tumor-generated proteases and promote tumor growth, invasion and metastasis.  Inappropriate regulation of PAR signaling in breast carcinoma due to dysregulated trafficking causes persistent signaling and cellular invasion. We study the function of PAR cross-talk with ErbB family members in breast carcinoma invasion and metastasis. We also study the function of PAR signaling in regulation of endothelial barrier permeability and the control breast carcinoma transendothelial cell migration.

Our laboratory is a highly interactive research team that is composed of postdoctoral fellows, graduate students and research associates. See Lab Members.

Recent Publications:

  • Wolfe, B.L., Marchese, A., and Trejo, J . (2007) Ubiquitination differentially regulates clathrin-dependent internalization of protease-activated receptor-1. J. Cell Biol 177:905-916. Abstract
  • Arora, P., Ricks, T.K., and Trejo, J. (2007) Protease-activated receptor signalling, endocytic sorting and dysregulation in cancer. (Review) Commentary. J. Cell Sci., 120:921-928. Abstract
  • Wolfe, B.L., and Trejo, J. (2007) Clathrin-dependent mechanisms of G protein-coupled    receptor endocytosis.  (Review) Traffic, 8:1-9. Abstract
  • Traynelis, S.F., and Trejo, J.(2007) Protease-activated receptor signaling: new roles and regulatory mechanisms.  (Review) Curr. Opin. Hematol., 14:230-235. Abstract
  • Paing, M.M., Johnston, C.A., Siderovski, D.P., and Trejo, J. ( 2006) Clathrin adaptor AP2 regulates thrombin receptor constitutive internalization and endothelial cell resensitization. Mol Cell Biol 26(8):3231-3242. Abstract
  • Camerer, E, and Trejo, J. (2006) Cryptic messages: Is non-coagulant tissue factor reserved for cell signaling? Commentary. Proc Natl Acad Sci 103(39): 14259-14260. Abstract
  • Gullapalli, A., Wolfe, B.L., Griffin, C.T., Magnuson, T., and Trejo, J. ( 2006) An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: Evidence for retromer, Hrs and Tsg101 independent functions of sorting nexins. Mol Biol Cell 17(3):1228-1238. Abstract
  • Dho, S.E., Trejo, J, Siderovski, D.P., and McGlade, C.J. (2006) Dynamic regulation of mammalian numb by GPCR and PKC activation: Structural determinants of numb association with the cortical membrane. Mol. Biol. Cell 17:4142-4155. Abstract
  • Morris, D.R., Ding, Y., Ricks, T.K., Gullapalli, A., Wolfe, B.L., and Trejo, J. ( 2006) Protease-activated receptor-2 is essential for factor VIIa and Xa-induced signaling, migration and invasion of breast cancer cells. Cancer Res 67(1):1-7. Abstract