Denise Wingett
Associate Professor
Department of Biology
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Denise Wingett
Associate Professor Department of Biology |
|
| Year arrived at BSU: | 2003 |
| Mailing Address: | Department of Biology, Boise State University, Boise, ID 83725-1515 |
| Office Location: | Science Nursing Building 102C |
| Office phone: | 208-426-2921 |
| FAX: | 208-426-4267 |
| e-mail address: | denisewingett@boisestate.edu |
Boise State University
Biology 310 Cell Biology, 2005-2007.
Biology 498/598 Infection and Immunity, 2006.
Biology 420/420G Immunology, 2005-2007.
Biology 446/546 Bioinformatics, 2003 and 2006.
Biology 466/566 Advanced topics in Cancer and Immunology, 2005.
Biology 297 Introduction to Bioinformatics, 2004.
Biology 497/597Advanced topic in Immunology, 1999.
Washington State University
Microbiology 412/512 Immunology, 1993
IMMUNOLOGY, HUMAN DISEASE, AND THERAPUETIC INTERVENTIONS
The overall focus of our laboratory investigates how the immune system is involved in the pathogenesis of human diseases, including asthma, autoimmunity and cancer, and novel ways to treat disease.
Asthma and beta-adrenergic agonists: A long standing interest of our laboratory has been to determine the underlying basis for the negative side effects of a commonly used class of asthma medications. Although beta-adrenergic agonists are effective in relieving the symptoms of asthma, serious concerns regarding their safety have persisted for more than 20 years. Recently, the FDA halted a large-scale study designed to examine the safety of these medications due to serious and life-threatening exacerbations and placed a black box warning on these drugs. In an effort to understand the molecular basis for adverse side effects, we have determined that an important regulatory protein (CD40L) expressed on T cells of the immune system is abnormally regulated by these drugs. Beta-agonists, by increasing cAMP levels in the cell, can elevate the expression of CD40L protein on T cells from asthmatics. This response is predicted to promote the underlying inflammatory responses contributing to disease. Conversely, beta-agonists decrease the expression of CD40L in healthy subjects. The goal of our research is to determine the molecular and cellular mechanisms leading to dysregulated CD40L protein expression in asthma. These finding should further our understanding of disease mechanisms, therapeutic intervention, and potentially lead to the identification of at-risk populations for adverse drug response.
Nanotechnology and biomedical applications: An active area of research in our lab is investigating the potential applications of metal oxide nanomaterials on the immune response and treatment of human diseases including cancer and autoimmunity. Nanoparticles (NP) with sizes in the 1 – 100 nm range, comparable to the sizes of naturally occurring biological molecules, are very attractive materials for manipulating biological structures and systems. When reduced to the nanoscale, many benign materials develop toxicity or other novel attributes, presumably due to the increased reactivity of the material surface. We have determined that different nanoparticle systems induce toxicity in a cell-specific and microenvironment-dependent manner. By controlling nanoparticle selectivity to specific cell types by design, we are currently exploring novel biomedical applications including drug delivery, cancer therapy, and treatment of immune disorders.
Novel drug candidates and inflammatory disease: We are investigating the potential utility of novel anthracycline drug analogs for the treatment of autoimmune diseases. The compound, DIDOX, belongs to a family of drugs called anthracyclines that are commonly prescribed for the treatment of cancer. Although anthracyclines have potent anti-proliferative effects that make them effective chemotherapeutic agents, a serious side effect of cardiotoxicity can develop 10-20 years later. A new drug analog, DIDOX, has been structurally modified to eliminate the molecular components associated with cardiotoxicity which opens the possibility of using this drug for the treatment of non-life threatening diseases such as psoriasis. We have determined that DIDOX effectively inhibits in vitro T cell responses as well as inflammatory responses in vivo. Future goals will be to evaluate the efficacy of this compound in animal models of psoriasis and other inflammatory diseases and to delineate the molecular mechanisms of immunosuppressive action.
1. Wyatt CR, Wingett D, White JS, Buck CD, Knowles D, Reeves D, and Magnuson NS: Persistent infection of rabbits with bovine leukemia virus associated with development of immune dysfunction. J Virol 63 :4498-4506, 1989.
2. Wingett D, Reeves R, and Magnuson NS: Stability changes in pim-1 proto-oncogene mRNA following mitogen stimulation of normal lymphocytes. J Immunol 147: 3563-3659, 1991.
3. Wingett D, Reeves R, and Magnuson NS: Characterization of the testes-specific Pim-1 transcript in rat. Nucleic Acids Res 20: 3183-3189, 1992.
4. Wingett D, Stone D, Davis WC, and Magnuson NS: Expression of the pim-1 proto-oncogene: Differential inducibility between alpha/beta and gamma/delta-T cells and B cells. Cell Immunol 162:123-130, 1995.
5. Wingett D, and Magnuson NS: Pim-1 proto-oncogene expression in anti‑CD3‑ mediated T cell activation is associated with protein kinase C activation and is independent of raf-1. J Immunol 156: 549-557, 1996.
6. Whitham RD, Wingett D, Wineman J, Mass M, Wegmann K, Vandenbark A, and Offner H: Treatment of relapsing autoimmune encephalomyelitis with T cell receptor V beta-specific antibodies when proteolipid protein is the autoantigen. J Neurosci Res 45: 104-116, 1996.
7. Wingett D, Forcier K, and Nielson CP: Glucocorticoid-medicated inhibition of RANTES expression in human T lymphocytes. Febs Lett 398:308-311, 1996.
8. Hoover DS, Wingett D, Zhang J, Reeves R, and Magnuson NS: Pim-1 protein expression is regulated by its 5’-untranslated region and translation initiation factor eIF-4E. Cell Growth Diff 8: 1371-1380, 1997.
9. Wingett D, Vestal RE, Forcier K, Hadjokas N, and Nielson CP: CD40 is functionally expressed on human breast carcinomas: Variable inducibility by cytokines and enhancement of Fas-mediated apoptosis. Breast Cancer Res Treat 50: 27-36, 1998.
10. Wingett D, Forcier K, and Nielson CP: Regulation of CD40L expression by cyclic AMP: Contrasting proinflammatory and inhibitory actions. Cell Immunol 192: 203-212, 1999.
11. Wingett D, Forcier K, and Nielson CP: A role for CD99 in T cell activation. Cell Immunol 193:17-23, 1999.
12. Nielson CP, and Wingett D: Endothelial cell and cAMP regulation of T cell CD40: Relevance of CaMKIV signaling. Immunol 105: 430-440, 2002.
13. Wingett D, and Nielson CP: Cyclic AMP differentially modulates CD40L expression on human naive and memory CD4+ T cells. Biochem Pharm 64: 1169-1178, 2002.
14. Wingett D, and Nielson CP: Divergence in NK cell and cyclic AMP regulation of T cell CD40L expression in asthmatic subjects. J Leuk Biol 74: 531-541, 2003.
15. Nielson C, and Wingett D: Intensive care and invasive ventilation in the elderly patient, implications of chronic lung disease and comorbidities. Chron Respir Dis 1: 43-54, 2004.
16. Matthies KGM, Hodzic A, and Wingett D: Differential regulation of soluble and membrane CD40L protein in T cells. Cell Immun 241: 47-58, 2006.
17. Olson RD, Headley MB, Walsh GM, and Wingett D: In vitro and in vivo immuno-suppressive activity of a novel anthracycline, 13-deoxy, 5-iminodoxorubicin. Int Immunopharmacol, 7: 734-743, 2007.
18. Reddy KM, Feris K, Bell J, Wingett DG, Hanley C, and Punnoose A: Selective toxicity of zinc oxide nanoparticles to prokaryotic and eukaryotic systems. Appl Phys Lett, 90: 213902, 2007.
19. Wang H, Wingett D, Engelhard ME, Feris K, Reddy KM, Turner P, Layne J, Hanley C, Bell J, Tenne D, Wang C, and Punnoose A: Fluorescent dye encapsulated ZnO particles with cell-specific toxicity for cancer treatment and bio-medical applications. Submitted 2007.
Undergraduate Students:
Mark Headley 2003-2004, Anti-inflammatory effects of a novel anthracycline drug analog, Boise State University
BRIN Summer Research Fellow, 2004
Undergraduate Research Symposium Presentation, 2004
Began Graduate School at Boise State University, 2004
Brandon Priebe, 2003-2004, Anti-inflammatory effects of a novel anthracycline drug analog, Boise State University
BRIN Summer Research Fellow, 2003
Began Dental School, 2004
Burke Hays, 2004, Proinflammatory effects of T cell costimulation and cyclic AMP, Boise State University and Albertson College of Idaho
BRIN Summer Research Fellow, 2004
Alma Hodzic, 2004-2005, Cloning and site-directed mutagenesis of T cell CD40L reporter gene constructs, Boise State University
Awarded BRIN Summer Research Fellow, 2005 (declined)
Began Graduate School at Boise State University, 2005
Sean Chronic, 2007, Toxicity effects of ZnO nanoparticles in cancer cell lines,
Boise State University
Graduate Student Research Projects:
Mark Headley, 2004-2005, Immunomodulatory properties of a novel anthracycline drug analog, M.S. awarded 2005, Boise State University
Began Doctoral Training, University of Washington 2005
Kelli Matthies, 2004-2006, Differential Regulation of Soluble and Membrane CD40L proteins in T cells, M.S. awarded 2006, Boise State University
Currently employed as a research scientist in the pharmaceutical industry
RR
Alma Hodzic, 2005-2007, Molecular mechanisms controlling T cell CD40L gene expression: implications for asthma, M.S. awarded 2007, Boise State University
Currently employed as a research scientist in the pharmaceutical industry
Cory Hanley, 2005-current, Effects of metal oxide based nanoparticles in immune response, Boise State University
Ashley Materson, 2006-current, Pro-inflammatory effects of cAMP in the regulation of T cell CD40L gene expression and asthma, Boise State University
Janet Layne, 2007-current, Toxicity effects of metal oxide nanoparticles in cancer, Boise State University