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Faculty Detail    
Name LAURIE E HARRINGTON
  
Campus Address BBRB 471- Zip 2170
Phone  (205) 996-9795
E-mail  lharring@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor
Center  Center for AIDS Research  Center for AIDS Research Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Ctr for Clinical & Translational Sci  Ctr for Clinical & Translational Sci Professor
Center  Multiple Sclerosis Center  Multiple Sclerosis Center Professor
Center  UAB Immunology Institute  UAB Immunology Institute Professor

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Immunology 
Microbiology 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Laurie E. Harrington received her B.S. degree from the University of Vermont in 1997 and her Ph.D. in Immunology from Emory University in 2001. In late 2001, she began her postdoctoral studies at the University of Alabama at Birmingham, investigating the heterogeneity of CD4 T cell responses during autoimmune and protective immune responses. Laurie joined the Department of Cell Biology, now Cell, Developmental and Integrative Biology, as an Assistant Professor in 2007.



Research/Clinical Interest
Title
Protective and Pathogenic CD4 T Cell Responses
Description
In my laboratory the focus will be on two main areas of research: (1) the roles of and lineage relationships between effector CD4 T cell subsets during chronic inflammatory disorders, and (2) the factors critical for the development and maintenance of CD4 T cell memory. (1) CD4 T cells have a vital role in the development of multiple autoimmune chronic inflammatory disorders. It is now appreciated that the onset of some of these chronic inflammatory diseases is associated with the induction of effector CD4 T cells, as well as with the decline in regulatory CD4 T cells. In my laboratory, two different murine disease models, experimental autoimmune encephalitis (EAE; a model for multiple sclerosis) and colitis, will be utilized to dissect the contributions of distinct subsets of effectors cells during chronic inflammation. The laboratory will employ/develop novel transgenic mice to identify cytokine-producing cells and understand their impact on autoimmunity. In addition to exploring how distinct subsets of effector CD4 T cells contribute to chronic inflammation, my laboratory will examine the role of specific transcription factors, specifically STAT4 and Tbet, in mediating pathogenesis. In the laboratory we will explore the essential roles for these transcription factors during disease pathogenesis by more closely examining the effector T cells as well as globally at gene regulation in the absence of these transcription factors, with the hopes that these studies may provide insights into the requirements, and thus potential targets, for chronic inflammation. (2) Memory T cells provide protection against secondary infections, and therefore it is critical to understand the mechanisms by which these cells differentiate. Data from my postdoctoral studies indicate that following an acute viral infection, effector CD4 T cells are capable of surviving long-term and transitioning into memory cells. In my laboratory, experiments will be performed to examine whether all effector cells can enter into the memory pool and if so, what factors are required not only for physical, but also functional maintenance. Moreover, the laboratory will examine the requirement for specific transcription factors in the development of functional effector and memory cells, as well as the role of these molecules in the functional recall response. These studies will provide information regarding the factors needed to maintain a functional memory compartment which is integral for the rational design of vaccines and therapeutic interventions.

Selected Publications 
Publication PUBMEDID
McWilliams, I.L., Rajbhandari, R., Nozell, S., Benveniste, E., and Harrington, L.E. STAT4 controls GM-CSF production by both Th1 and Th17 cells during EAE. Journal of Neuroinflammation (in press).   
Yeh, W.I., McWilliams, I.L., and Harrington, L.E. IFNγ inhibits Th17 differentiation and function via Tbet-dependent and Tbet-independent mechanisms. (2014) Journal of Neuroimmunology 267:20-27.  24369297 
Mollo, S.B., Ingram, J.T., Kress, R.L., Zajac, A.J., and Harrington, L.E. Virus-specific CD4 and CD8 T cell responses in the absence of Th1-associated transcription factors. (2014) Journal of Leukocyte Biology 95:705-713.  24231259 
Mollo, S.B., Zajac, A.J., and Harrington, L.E. Temporal requirements for B cells in the establishment of CD4 T cell memory. (2013) The Journal of Immunology 191(12):6052-9.  24218454 
Beurel, E., Kaidanovich-Beilin, O., Yeh, W.I., Song, L., Palomo, V., Michalek, S.M., Woodgett, J.R., Harrington, L.E., Eldar-Finkelman, H., Martinez, A., Jope, R.S. Regulation of Th1 cells and experimental autoimmune encephalomyelitis by glycogen synthase kinase-3. (2013) The Journal of Immunology 190(10):5000-11.  23606540 
Qin, H., Yeh, W.I., De Sarno, P., Holdbrooks, A.T., Liu, Y., Muldowney, M.T., Reynolds, S.L., Yanagisawa, L.L., Fox, T.H. 3rd, Park, K., Harrington, L.E., Raman, C., Benveniste, E.N. Signal transducer and activator of transcription-3/suppressor of cytokine signaling-3 (STAT3/SOCS3) axis in myeloid cells regulates neuroinflammation. (2012) Proc Natl Acad Sci U S A. 109(13):5004-5009.  22411837  
Yeh, W.I., McWilliams, I.L., and Harrington, L.E. Autoreactive Tbet-positive CD4 T Cells Develop Independent of Classic Th1 Cytokine Signaling during EAE. (2011) The Journal of Immunology 187:4998-5006.  21984703 
Beurel, E., Yeh, W.I., Michalek, S.M., Harrington, L.E., and Jope, R.S. Glycogen synthase kinase-3 is an early determinant in the differentiation of pathogenic Th17 cells. (2011) The Journal of Immunology 186:1391-1398.  21191064 
Mackerness, K.J., Cox, M.A., Lilly, L.M., Weaver, C.T., Harrington, L.E., and Zajac, A.J. Pronounced virus-dependent activation drives exhaustion but sustains Interferon-g transcript levels. (2010) The Journal of Immunology 185:3643-3651.  20720198 
Harrington, L.E., Janowski, K.M., Oliver, J., Zajac, A.J., and Weaver, C.T. Memory CD4 T cells emerge from an IFNg competent effector cell population. (2008) Nature 452:356-360.  18322463 
Maynard, C.L., Harrington, L.E., Janowski, K.M., Oliver, J.R., Zindl, C.L., Rudensky, A.Y., and Weaver, C.T. Regulatory T cells expressing interleukin-10 develop from Foxp3+ and Foxp3- precursor cells in the absence of interleukin-10. (2007) Nature Immunology 8:931-41.  17694059 
Weaver, C.T., Hatton, R.D., Mangan, P.R., and Harrington, L.E. IL-17 family cytokines and the expanding diversity of effector T cell lineages. (2007) Annual Reviews in Immunology 25:821-852.  17201677 
Hatton, R.D., Harrington, L.E., Luther, R., Wakefield, T., Murphy, K.M., and Weaver, C.T. A distal conserved sequence element controls Ifng gene expression by T cells and NK cells. (2006) Immunity 25:717-729.  17070076 
Mangan, P.R., Harrington, L.E., O’Quinn, D.B., Helms, W.S., Bullard, D.C., Elson, C.O., Hatton, R.D., Wahl, S.M., Schoeb, T.R., and Weaver, C.T. Transforming growth factor-beta induces development of the T(H)17 lineage. (2006) Nature 441:231-234.  16648837 
Harrington, L.E., Mangan, P.R., and Weaver, C.T. Expanding the effector CD4 T-cell repertoire: the Th17 lineage. (2006) Current Opinion in Immunology 18:349-356.   16616472 
Harrington, L.E., Hatton, R.D., Mangan, P.R., Turner, H., Murphy, T.L., Murphy, K.M., and Weaver, C.T. IL-17-producing CD4 effector T cells develop via a lineage distinct from Th1 and Th2. (2005) Nature Immunology 6:1123-1132.  16200070 
Harrington, L.E., van der Most, R.G., Whitton, J.L., and Ahmed, R. Recombinant vaccinia virus induced T cell immunity: quantitation of the response to the virus vector and the foreign epitope. (2002) Journal of Virology 76: 3329-3337.   11884558  
Harrington, L.E., Galvan, M., Baum, L.G., Altman, J.D., and Ahmed, R. Differentiating between memory and effector CD8 T cells by altered expression of cell surface O-glycans. (2000) Journal of Experimental Medicine 191:1241-1246.  10748241 
 

Keywords
CD4 T cells, autoimmunity, immunological memory, cytokines