 Ph.D. (1992) |
Deborah
Fowell
Associate Professor of Microbiology & Immunology Primary Academic Appointment: Center Affiliation: GEBS Cluster Affiliations: |
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| Contact Information: |
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| University
of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box 609 Rochester, New York 14642 |
Phone:
(585) 273-3680 Fax: (585) 273-2452 E-Mail: deborah_fowell@urmc.rochester.edu Fowell Lab Group |
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- Research Focus
- Differentiation of CD4 T lymphocytes in infectious and autoimmune disease.
- Research Overview
- Upon antigen challenge, CD4+ (helper) T cells develop from uncommitted precursors into terminally differentiated effector T cells characterized by discrete cytokine gene expression patterns. Th1 effectors (via interferon-gamma and lymphotoxin production) efficiently confront intracellular pathogens through activation of phagocytes and cytotoxic lymphocytes. Conversely, Th2 effectors (via interleukin-4 (IL-4) IL-5 and IL-13 secretion) mediate mucosal immunity and the expulsion of intestinal helminths. Importantly, Th1 and Th2 cells antagonize the growth and biological effects of one another leading to highly polarized populations on immune challenge. Many disease states, both autoimmune and infectious, result from the development of a robust immune response that has been inappropriately polarized. We are interested in how these effector populations are established. Our data suggests multiple check points in effector differentiation, at least one at the level of T cell signaling on initial activation and one at the population level for expansion and survival of effectors.
- A critical component of the immune system is tight regulation; ensuring appropriate termination of immune responses following pathogen clearance and avoiding the inappropriate activation of immune responses to self tissues resulting in autoimmunity. Regulation is in part mediated by a distinct CD4+ T lineage called regulatory T cells (T regs). Removal of T regs from the immune system renders rodents susceptible to multiple autoimmune diseases. We are interested in the signals that drive differentiation of T regs and the mechanisms of their regulatory activity.
- We exploit the genetics of susceptibility to disease in inbred mouse strains to uncover important cellular and molecular components of effector T cell development. Our current studies focus on the basic mechanisms that regulate effector T cell differentiation, including:
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- Lymphocyte signaling for effector lineage commitment (Immunity
11:399, Immunity 6:559)
- Development of immune responses in vivo following
parasite infection (Bioessays 21:510)
- Development and activity of regulatory T cells in prevention of autoimmune disease.
- Lymphocyte signaling for effector lineage commitment (Immunity
11:399, Immunity 6:559)
- Click here to see recent images of the Fowell Lab Group.
- Recent Publications
- Sojka DK, Huang YH, Fowell DJ Mechanisms of regulatory T-cell suppression - a diverse arsenal for a moving target. Immunology. 2008 Mar 14;
- Katzman SD, Fowell DJ "Pathogen-imposed skewing of mouse chemokine and cytokine expression at the infected tissue site." J Clin Invest. 2008 Jan 10;
- Zhao X, Zheng B, Huang Y, Yang D, Katzman S, Chang C, Fowell D, Zeng WP "Interaction between GATA-3 and the Transcriptional Coregulator Pias1 Is Important for the Regulation of Th2 Immune Responses." J Immunol. 2007 Dec 15;179(12):8297-304
- Au-Yeung BB, Fowell DJ "A Key Role for Itk in Both IFN{gamma} and IL-4 Production by NKT Cells." J Immunol. 2007 Jul 1;179(1):111-9
- Sukiennicki TL, Fowell DJ "Distinct Molecular Program Imposed on CD4+ T Cell Targets by CD4+CD25+ Regulatory T Cells." J Immunol. 2006 Nov 15;177(10):6952-61
- Kobie JJ, Shah PR, Yang L, Rebhahn JA, Fowell DJ, Mosmann TR. "T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 5'-adenosine monophosphate to adenosine." J Immunol. 2006 Nov 15;177(10):6780-6
- Au-Yeung BB, Katzman SD, Fowell DJ. "Cutting edge: Itk-dependent signals required for CD4+ T cells to exert, but not gain, Th2 effector function." J Immunol. 2006 Apr 1;176(7):3895-9.
- Sojka DK, Hughson A, Sukiennicki TL, Fowell DJ. "Early kinetic window of target T cell susceptibility to CD25+ regulatory T cell activity." J Immunol. 2005 Dec 1;175(11):7274-80.
- Morales-Tirado V, Johannson S, Hanson E, Howell A, Zhang J, Siminovitch KA, Fowell DJ. "Cutting edge: selective requirement for the Wiskott-Aldrich syndrome protein in cytokine, but not chemokine, secretion by CD4+ T cells." J Immunol. 173:726-30, 2004.
- Mosmann T, Fowell DJ. The Th1/Th2 paradigm in infections. Editors: Kaufmann SHE, Sher A, Ahmed R: Immunology of Infectious Diseases. ASM Press, 2001.
- Gurunathan S, Stobie L, Prussin C, Sacks DL, Glaichenhaus N, Fowell DJ, Locksley RM, Chang JT, Wu CY, Seder RA. Requirements for the maintenance of Th1 immunity in vivo following DNA vaccination: a potential immunoregulatory role for CD8+ T cells. J Immunol. 165:915-24, 2000.
- Pippig SD, Pena-Rossi C, Long J, Godfrey WR, Fowell DJ, Reiner SL, Birkeland ML, Locksley RM, Barclay AN, Killeen N. Robust B cell immunity but impaired T cell proliferation in the absence of CD134 (OX40). J Immunol. 163:6520-9, 1999.
- Heath VL, Hutchings P, Fowell DJ, Cooke A, Mason DW. Peptides derived from murine insulin are diabetogenic in both rats and mice, but the disease-inducing epitopes are different: evidence against a common environmental cross-reactivity in the pathogenicity of type 1 diabetes. Diabetes. 48:2157-65, 1999.
- Fowell DJ, Shinkai K, Liao XC, Beebe AM, Coffman RL, Littman DR, Locksley RM. Impaired NFATc translocation and failure of Th2 development in itk-deficient CD4+ T cells. Immunity 11:399-409, 1999.
- Fowell DJ, Locksley RM. Leishmania major infection of inbred mice: unmasking genetic determinants of infectious diseases. BioEssays 21:510-8, 1999.
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