M.S. California State Polytechnic University, Pomona, 1992
Ph.D. Oregon Health & Science University, Portland, OR, 2001
1996 - 2004Â Â Â Â Instructor, Medical School Immunology, Oregon Health & Science University, Portland, OR
1997 - 2004Â Â Â Â Instructor, Clinical Laboratory Science Program, Oregon Health & Science University, Portland, OR
2002 â€“ 2004Â Â Â Instructor, Biotechnology Department, Portland Community College, Portland, OR
2002 â€“ 2011Â Â Â Faculty Member, Annual International Course on 3D Microscopy of Living Cells, University ofÂ British Columbia, Vancouver, BC, Canada
Work in my lab focuses on antigen recognition and activation of CD4+ T lymphocytes.
CD4+Â T lymphocytes recognize antigenic peptide fragments presented on the surface of antigen presenting cells (APC) by major histocompatiblility complex (MHC) class II proteins. Triggering of the T cell antigen receptor (TCR) by binding to the MHC:peptide ligand induces dramatic morphological changes as the T cell flattens against the APC and increases contact area forming stable T-APC conjugates. This initial antigen recognition is followed by large-scale spatial and temporal molecular rearrangements of plasma membrane proteins and intracellular signaling molecules. These rearrangements lead to the formation of an ordered structure at the T-APC interface termed theÂ immunological synapse. The synapse is involved in T cell signaling as well as the site for delivery of T cell effector functions. We have previously shown that molecules from the APC are transferred to the T cell across the immune synapse in a process called trogocytosis.
Work in our lab focuses on two important areas related to T lymphocyte biology:
â€¢ Â The biological consequences for individual T cells after the capture of APC membrane fragments from T-APC immunological synapse, a process termed â€œtrogocytosisâ€쳌;
â€¢ Â The impact of the herbicide Atrazine on the activation of CD4+ T cells and the mechanism underlying a significant increase in Foxp3+ regulatory T cells
We are examining the biological significance of intercellular transfer of molecules from APC to T cells (termed trogocytosis). We have previously shown that upon dissociation from APC, T cells capture MHC:peptide molecules from the immunological synapse and imaging data suggests that these molecules continue to signal to the T cell. Our work suggests that these trogocytosed molecules sustain intracellular signalingÂ leading to selective survival of the trogocytosis positive cells, in vitro. Â We are currently investigating whether this signaling influences effector subset differentiation and effector cytokine production. Our working hypothesis is that trogocytosisÂ contributes to control of theÂ immune response by sustainingÂ cell-autonomous signaling resulting in sustained effector cytokine production and skewing of CD4+ T cells to a TH2-like phenotype.Â
Immunotoxicology of Atrazine
We are examining the impact on Atrazine on thethe activation and differentiation of CD4+ T cells. Â Atrazine is a very widely applied herbicide that the USGS Â estimates contaminates 70% of the ground water in the US. It has been linked to birth defects, Â cancer, immune developmental defects andÂ modulation of immune cell effector functions. We have shown that Atrazine inhibits lymphocyte proliferation and lymphocyte effector function. Â In addition, we have shown that the frequency of Foxp3 positive regulatory T cells doubles in atrazine-treated cultures. We have recently found that male and female T cells repsonde differently to atrazine exposure. Â We are now examining the impact of Atrazine-induced elevated estrogen on the induction of Tregs and Atrazine-associated inhibion of T cell activation.
American Association of Immunologists
University of Montana Center for Environmental Health Sciences
Scientific Director, University of Montana Molecular Histology and Fluorescence Imaging Core Facility
UM Interdepartmental Immunology Graduate Degree Track
UM DBS Cellular, Molecular, Microbial Biology Graduate Program