Faculty Profile


Scott Wetzel

Scott Wetzel

Associate Professor

Email: scott.wetzel@umontana.edu
Office: Charles H. Clapp Building, Room 216
Personal Website
Curriculum Vitae

Current Position

Associate Professor of Immunobiology

Scientific Director, Molecular Histology and Fluorescence Imaging Core Facility

Scientific Director, EMTrix (UM Electron Microscopy Core Facility)

Courses

BIOB 410 - Immunology

BIOB 411 - Immunology Lab

BIOM 502 - Advanced Immunology

BIOB 596 - Principles of Light Microscopy

Education

B.A. University of La Verne, La Verne, CA., 1987

M.S. California State Polytechnic University, Pomona, 1992

Ph.D. Oregon Health & Science University, Portland, OR, 2001

Research Interests

Work in my lab focuses on the activation and subset differentiation of CD4+ T lymphocytes.

  • The biological consequences for individual T cells after the capture of APC membrane fragments from T-APC immunological synapse, a process termed “trogocytosis”;
  • 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

Trogocytosis 

CD4+ 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 the 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.

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 signaling leading to selective survival of the trogocytosis positive cells, in vitro.  More recent work has shown that this trogocytosis-mediated signaling contributes to the control of the immune response by sustaining effector cytokine production and the skewing of CD4+ T cells to a TH2 and/or TFH phenotype.

Immunotoxicology of Atrazine

We are examining the impact on Atrazine on the activation and differentiation of CD4+ T cells.  Atrazine is a very widely applied herbicide that the USGS  estimates contaminates 70% of the ground water in the US. It has been linked to birth defects, cancer, immune developmental defects and  modulation of immune cell effector functions. We have shown that Atrazine inhibits CD4+ T lymphocyte proliferation and effector function.  In addition, we have shown that the frequency of Foxp3 positive regulatory T cells (Treg) doubles in atrazine-treated cultures. This is largely due to elevated levels of cAMP, as Atrazine is a potent phosphidiesterase inhibitor.  We have recently found that male and female T cells repsond differently to atrazine exposure.  Atrazine's other biochemical effect is to induce expression of aromatase, which converts androgens to estrogen. We are now examining the impact of Atrazine-induced elevated estrogen on the induction of Tregs and Atrazine-associated inhibion of T cell activation.

Field of Study

Cellular Immunology

Immunotoxicology

Selected Publications

Publications

Thueson, L.E; Emmons, .E., Browning, D.B., Kreitinger, J.M.; Sheherd, D.M.; Wetzel S.A.  (2015). In vitro Exposure To The Herbicide Atrazine Inhibits T Cell Activation, Proliferation, and Cytokine Production and Significantly Increases The Frequency Of Foxp3+ Regulatory T Cells. Toxicological Sciences. 143:418-29. PMID: 25433234

Osborne, D.G. and Wetzel, S.A. (2012) Trogocytosis leads to sustained signaling in CD4+ T cells. The Journal of Immunology, 189(10):4728-39.  PMID: 23066151

Doherty, M., Osborne, D.G., Browning, D.B., Parker, D.C. Wetzel, S.A. (2010) Anergic CD4+ T cells form mature immunological synapses with enhanced accumulation of c-Cbl and Cbl-b. The Journal of Immunology, 184:3598-3608.  PMCID: PMC2843782

Thauland, T.J.; Y. Koguchi, R.Varma, S.A. Wetzel, M.L. Dustin, and D.C. Parker. (2008).  TH1 and TH2 cells fom morphologically distinct immunological synapses .  The Journal of Immunology,  181:393-9

Blake, D.J.; Wetzel, S.A.; Jean C Pfau, J.C. (2008) Autoantibodies from mice exposed to Libby amphibole asbestos bind SSA/Ro52-enriched apoptotic blebs of murine macrophages. Toxicology, 246:172-9

Scott A. Wetzel and D.C. Parker. (2006) MHC transfer from APC to T cells following antigen recognition. Critical Reviews in Immunology. 26:1-21

Tara J. Dillon, K.D.Carey, S.A. Wetzel, D.C. Parker, P.J.S. Stork. (2005). Regulation of the Small GTPase Rap1 and Extracellular Signal-Regulated Kinases by the Costimulatory Molecule CTLA-4. Molecular Cell Biology, 25(10):4117-4128

Scott A. Wetzel, T. W. McKeithan, D.C. Parker. (2005). Peptide-specific intercellular transfer of MHC class II to CD4+ T cells directly from the immunological synapse upon cellular dissociation. The Journal of Immunology. 174(1): 80-9

Tara J. Dillon, Vladimir Karpitski, Scott A. Wetzel, David C. Parker, Andrey S. Shaw, and Philip J. S. Stork (2003). Ectopic B-Raf expression enhances extracellular signal-regulated kinase (ERK) Signaling in T cells and prevents antigen presenting cell-induced anergy. Journal of Biological Chemistry, 278:35940.

Wetzel, S.A. ; McKeithan, T.W.; Parker D.C. (2002) Live Cell Dynamics and the Role of Costimulation in Immunological Synapse Formation. The Journal of Immunology. 169(11):6092

Sperry P.J.; Cua D.J.; Wetzel S.A.; Adler-Moore, J.A. (1998) Antimicrobial activity of AmBisome and non-liposomal Amphotericin B following uptake of Candida glabrata by murine epidermal Langerhans cells. Medical Mycology 36(3):135 - 141

Primus, F.J.; Finch, M.D.; Wetzel, S.A.; Masci, A.M.; Schlom, J.; Kashmiri, S.V.S. (1994) Monoclonal Antibody Gene Transfer: Implications for Tumor - Specific Cell - Mediated Cytotoxicity. Annals of the New York Academy of Science. 716:154 - 166

Outreach

https://www.researchgate.net/profile/Scott_Wetzel

 

Specialized Research Interests

Trogocytosis, T cell signaling and Immunological synapse biology.

 

Teaching Experience

1996 - 2004        Instructor, Medical School Immunology, Oregon Health & Science University, Portland, OR

1997 - 2004        Instructor, Clinical Laboratory Science Program, Oregon Health & Science University, Portland, OR

2002 – 2004       Instructor, Biotechnology Department, Portland Community College, Portland, OR

2002 – 2011        Faculty Member, International Course on 3D Microscopy of Living Cells, University of British Columbia, Vancouver, BC, Canada

2005 - 2013        Assistant Professor, Division of Biological Sciences and Center for Environmental Health Sciences, University of Montana, Missoula, MT

2013 - Present    Associate Professor, Division of Biological Sciences and Center for Environmental Health Sciences, University of Montana, Missoula, MT

 

 

Affiliations

American Association of Immunologists

University of Montana Center for Environmental Health Sciences

UM Interdepartmental Immunology Graduate Degree Track

UM DBS Cellular, Molecular, Microbial Biology Graduate Program

UM Molecular Bioscience Gratuate Program