QUICK LINKS 


  • Link1
  • Link2
  • Link3

 
Denise Wingett
Associate Professor, Department of Biological Sciences
Department: Biological Sciences
Year arrived at BSU: 2003
Mailing Address:

Department of Biology
Boise State University
Boise, ID 83725-1515
Office Location: Science/Nursing 102C
Office Number: 208-426-2921
Office Fax: 208-426-1040
E-Mail Address: denisewingett@boisestate.edu
Academic Degrees | Teaching | Reseach Interests | Recent Publications | Graduate Students
   
ACADEMIC DEGREES
 
  • B.S., Boise State University, Chemistry, 1986
  • Ph.D., Washington State University, Biophysics and Biochemistry, 1991
  • Postdoctoral Fellow, Washington State University, Microbiology Dept., 1992-1994
  • Research Assistant Professor, Neuroimmunology Dept., Portland VA Medical Center/Oregon Health Sciences University, 1994-1995
  • Afilliate Faculty, Boise VA Medical Center, 1995-1998
  • Medical Research Scientist, Boise VA Medical Center, 1998-present
  • Assistant Research Professor, Div. of Gerontology and Geriatric Medicine, Univ. Washington School of Medicine, 2002-present
TEACHING
 
  • Biology 297 Introduction to Bioinformatics
  • Biology 310 Cell Biology
  • Biology 420/420G Immunology
  • Biology 446/546 Bioinformatics
  • Biology 466/566 Advanced topics in Cancer and Immunology
  • Biology 497/597Advanced topics in Immunology
  • Biology 498/598 Infection and Immunity

 
RESEARCH INTERESTS
 

IMMUNOLOGY, NANOBIOLOGY, AND THERAPUETIC INTERVENTIONS FOR HUMAN DISEASE

 

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 including nanotechnology based approaches.

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 oxidenanomaterials on the immune response and treatment of human diseases including cancerCancer cells killed by nanoparticles and autoimmunity. Nanoparticles 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 cancer therapy and drug delivery.


Cancer cells killed by nanoparticles

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. 

 

 
RECENT PUBLICATIONS [click to open]
  • 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 immune dysfunction. J Virol  63: 4498-4506,1989.

  • Wingett D, Reeves R, and Magnuson NS: Stability changes in pim-1 proto-oncogene mRNA following mitogen stimulation of normal lymphocytes. J Immunol  147: 3653‑3659, 1991.

  • Wingett D, Reeves R, and Magnuson NS:  Characterization of the testes-specific pim-1 transcript in rat. Nucleic Acids Res 20: 3183-3189, 1992.

  • 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.

  • Wingett D, Long A, Kelleher 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.

  • 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 proteo-lipidprotein is the autoantigen. J Neurosci Res 45: 104-116, 1996.

  • Wingett D, Forcier K, and Nielson CP: Glucocorticoid-medicated inhibition of RANTES expression in human T lymphocytes. Febs Lett 398: 308-311, 1996.

  • 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.

  • 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.

  • 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.

  • Wingett D, Forcier K, and Nielson CP: A role for CD99 in T cell activation. Cell Immunol 193: 17-23, 1999.

  • Nielson CP, and Wingett D: Endothelial cell and cAMP regulation of T-cell CD40 ligand: relevance of calcium/calmodulin-dependent kinase IV signaling. Immunol 105: 430-440, 2002.

  • 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.

  • 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.

  • Nielson CP, 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.

  • Matthies KGM, Hodzic A, and Wingett D: Differential regulation of soluble and membrane CD40L protein in T cells. Cell Immunol 241: 47-58, 2006.

  • Olson RD, Headley MB, Hodzic A, Walsh GM, and Wingett D: In Vitro and In Vivo Immunosuppressive Activity of a Novel Anthracycline, 13-deoxy, 5-iminodoxorubicin. International Immunopharmacology, 7: 734-743, 2007.

  • Kongara MR, Feris K, Bell J, Wingett DG, Hanley C, and Punnoose A: Selective toxicity of zinc oxide nanoparticles to prokaryotic and eukaryotic systems.  Applied Physics Letters, 90: 213901-213902, 2007.

  • Hanley C, Layne J, Punnoose A, Reddy KM, Coombs I, Coombs A, Feris K, and Wingett D: Preferential killing of cancer cells and activated human T cells using zinc oxide nanoparticles, Nanotechnology, 19, 1-10, 2008.

  • Wang H, Wingett D, Engelhard MH, Reddy KM, Layne J, Turner P, Feris K, Tenne D, Wang C, and  Punnoose A:  FITC encapsulated fluorescent ZnO particles with cell-specific toxicity for cancer treatment and biomedical applications, Journal of Material Science: Materials in Medicine, in press, 2008.

  • Masterson A, and Wingett D: Functional and phenotypic differences of natural killer cells from asthmatics, in preparation.
   
GRADUATE & UNDERGRADUATE STUDENTS
 
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
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

Nathan Dewey 2008, Toxicity effects of metal oxide nanoparticles in cancer cells
Boise State University

 

 

Graduate Students
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..

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
2006-current, Effects of metal oxide based nanoparticles in immune response, Boise State University.
Ashley Masterson
2006-current, Pro-inflammatory effects of cAMP in the regulation of T cell CD40L gene expression and asthma, Boise State University.
Awarded NSF G K-12 Fellowship, 2008. 

Janet Layne
2007-current, Toxicity effects of metal oxide nanoparticles in cancer, Boise State University. Boise State University.