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Amy S. McKee, PhD- Assistant Professor

Division of Allergy and Clinical Immunology


12700 E. 19th Avenue, B164, R2

Aurora, CO 80045

Phone: 303-724-7214

Fax: 303-724-7212

Amy.McKee@ucdenver.edu

1993-1997 BS (Biology) Colorado State University, Ft. Collins, CO
1997-1998 MS (Anatomy and Neurobiology) Colorado State University, Ft. Collins, CO
1998-2003 PhD (Immunology) Cornell University, Ithaca, NY
2004-2010 Postdoctoral Fellow, HHMI and National Jewish Medical Center, Denver, CO
2011-2013 Instructor, University of Colorado Denver, Aurora, CO

Innate immune receptor-mediated activation of dendritic cells

Pathogenesis of T-cell mediated granulomatous inflammation

Cellular and molecular basis of metal and particulate adjuvant activity

The primary focus of my laboratory is to dissect the mechanisms by which the metals aluminum and beryllium enhance T cell responses via effects on the innate immune system (i.e. act as adjuvants).  Aluminum salts have been used as adjuvants in human subunit vaccines for over a century with very little understanding of how they enhance T cell and antibody responses. Beryllium salts also have adjuvant properties. However beryllium exposure leads to debilitating pulmonary lung disease (chronic beryllium disease or berylliosis) in genetically susceptible individuals. Dendritic cells (DCs) are innate immune cells distributed throughout peripheral tissues and express a variety of innate immune receptors. Engagement of innate immune receptors on DCs alters the expression of genes in DCs that lead to their accelerated migration from peripheral tissues to draining lymph nodes where naive T cells circulate. Their increased presence and expression of costimulatory molecules enable them to induce expansion and differentiation of naive CD4 T cells into effector and memory T cells. We are currently studying the innate immune receptor pathways activated in response to aluminum or beryllium exposure and the effects that these pathways have on DC migration and T cell priming. Ultimately, we aim to determine how metals are recognized by the innate immune system, the molecular mechanisms behind the adjuvant properties of metals and the role that the innate immune system plays in the pathogenesis of chronic beryllium disease.

McKee AS, Mack DG, Crawford F and Fontenot AP. MyD88 Dependence of Beryllium-Induced Dendritic Cell Trafficking and CD4+ T Cell Priming. Mucosal Immunol. 2015; Advance Online Publication.
 
Mack DG, Falta MT, McKee AS, Martin AK, Simonian PL, Crawford F, Gordon T, Mercer RR, Hoover MD, Marrack P, Kappler JW, Tuder RM, Fontenot AP. Regulatory T cells modulate granulomatous inflammation in an HLA-DP2 transgenic murine model of beryllium-induced disease. Proc Natl Acad Sci U S A. 2014; 111:8553-8.
 
McKee AS, Burchill MA, Munks MW, Jin L, Kappler J, Friedman RS, Jacobelli J, and Marrack P. Host DNA released in response to aluminum adjuvant enhances MHC class II-mediated antigen presentation and prolongs CD4 T-cell interactions with dendritic cells. Proc. Natl. Acad. Sci. U S A. 2013; 110:E1122-31.
Dai S. Falta MT, Bowerman NA, McKee AS, Fontenot AP. T cell recognition of beryllium. Curr Opin Immunol. 2013; pii: S0952-7915(13)00127-1.
Huang Y, Aydintug MK, Loomis J, Macleod MK, McKee AS, Kirchenbaum G, Jakubzick CV, Kedl RM, Sun D, Jacobelli J, O'Brien RL, Born WK. Antigen-Specific Regulation of IgE Antibodies by Non-Antigen-Specific gamma-delta T Cells. J Immunol. 2013; 190: 913-21.
Macleod MK, McKee AS, David A, Wang J, Mason R, Kappler JW, Marrack P. Vaccine adjuvants aluminum and monophosphoryl lipid A provide distinct signals to generate protective cytotoxic memory CD8 T cells. Proc Natl Acad Sci U S A. 2011; 108:7914-9.
MacLeod M, David A, McKee AS, Crawford F, Kappler JW, and Marrack, P. CD4 memory T cells provide accelerated B cell help because they express CXCR5. J Immunol. 2011; 186:2889-96.
McKee AS, MacLeod, MK, Kappler, JW, and Marrack, P. Immune mechanisms of protection: can adjuvants rise to the challenge? BMC Biol. 2010; 8:37.
Munks MW, McKee AS, MacLeod M, Powell R, Brinkmann V, Zychlisky A, Degan JL, Reisdorf N, Kappler JW, and Marrack P. Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo. Blood. 2010; 116:5191-9.
 
McKee AS, Munks, MW, MacLeod, MK, Fleenor, CJ, Van Rooijen, N., Kappler JW, Marrack P. Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to work as an adjuvant for specific immunity. J Immunol. 2009; 183:4403-14.
 
Marrack P, McKee AS, Munks, MW. Towards an understanding of the adjuvant action of aluminum. Nat Rev Immunol. 2009; 9:287-93.
 
MacLeod M, McKee AS, Crawford F, White J, Kappler J, Marrack P. CD4 memory T cells divide poorly in response to antigen because of their cytokine profile. Proc. Natl. Acad. Sci. U S A. 2008;105:14521-6.
 
McKee AS, Munks M, Marrack P. How do adjuvants work? Important considerations for new generation adjuvants. Immunity. 2007; 27(687-690).
 
McKee AS, MacLeod M, White J, Crawford F, Kappler J and Marrack P. Gr1+IL-4 producing innate cells are induced in response to Th2 stimuli and suppress Th-1 dependent antibody responses. Int Immunol. 2008; 20:659-69.
 
Jorgensen T, McKee AS, Wang M, Kushnir E, White J, Kappler J, Marrack P. Bim and Bcl-2 mutually affect each other’s expression. J Immunol. 2007; 179: 3417-24.
 
Kane CM, Cervi L, Sun J, McKee AS, Masek KS, Shapira S, Hunter CA, Pearce EJ. Helminth antigens modulate TLR-initiated dendritic cell activation. J Immunol. 2004; 173:7454-61.
 
Pearce EJ, M Kane C, Sun J, J Taylor J, McKee AS, Cervi L. Th2 response polarization during infection with the helminth parasite Schistosoma mansoni. Immunol Rev. 2004; 201:117-26.
 
McKee AS, Dzierszinski F, Boes M, Roos DS, Pearce EJ. Functional inactivation of immature dendritic cells by the intracellular parasite Toxoplasma gondii. J Immunol. 2004; 173:2632-40.
 
McKee AS, Pearce EJ. CD25+CD4+ cells contribute to Th2 polarization during helminth infection by suppressing Th1 response development. J Immunol. 2004; 173:1224-3.
 
Straw AD, MacDonald AS, Denkers EY, Pearce EJ. CD154 plays a central role in regulating dendritic cell activation during infections that induce Th1 or Th2 responses. J Immunol. 2003; 170:727-734.
 
MacDonald AS, Straw AD, Dalton NM, Pearce EJ. Cutting edge: Th2 response induction by dendritic cells: a role for CD40. J Immunol. 2002; 168:537-40.
 
MacDonald AS, Straw AD, Bauman B, Pearce EJ. 2001. CD8a- dendritic cell activation status plays a critical role in influencing Th2 response development. J Immunol. 2001; 167:1982-8.