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Deborah J. Fowell, Ph.D.

Contact Information

Phone Numbers

Administrative: (585) 273-1400

Office: (585) 273-3680

Fax: (585) 273-2452

Research Labs

Lab: (585) 273-2902

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Program for Advanced Immune Bioimaging

Lab: (585) 273-2902

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Biography

Research

Regulation of Immunity at Tissue Sites of Infection and Autoimmunity

The acquisition and execution of CD4 effector function are tightly regulated and spatially compartmentalized. In the lymph node (LN), naïve CD4+ T cells acquire specialized functions by means of expression of distinct cytokines and acquire distinct homing properties. Therefore both the function and subsequent localization of effector cells appears to be pre-determined during differentiation in the LN. However, once CD4 effectors leave the lymph node their physical and functional fate is less well understood. The location and inflammatory context in which effector T cells are reactivated at the infection site are likely to determine the success of a given immune response. Our research focuses on mechanisms of immune regulation at tissue sites of inflammation.

Our studies with the protozoa Leishmania major suggest that this centrally (LN) generated effector repertoire can be further edited at the infected tissue site. Cytokine production in the inflamed tissue can be modulated at a number of levels including chemokine-driven differential recruitment of effector cells, the provision of signals for effector cell function and suppression by regulatory T cells (Tregs). The concept that tissue resident pathogens may subvert the centrally generated cytokine repertoire has important therapeutic implications. Novel therapies that focus on manipulating the local infection site to encourage appropriate recruitment or activation of effectors may be particularly beneficial.

Regulatory T cells play important immuno-modulatory roles at sites of inflammation in both infection and autoimmunity. Nonetheless, their mode of suppression remains controversial and is likely to be context dependent and modified by the inflammatory milieu. We focus on the molecular consequences of Treg encounter for the CD4+ T cells and have identified important points of control for early IL-2 production and for Th differentiation and effector function. Regulatory T cells can readily be found at sites of inflammation in infectious and autoimmune settings. It is clear that their activity also needs to be regulated in order to enable protective immunity to proceed but that these mechanisms of control may exacerbate autoimmune pathology. We are interested in the functional fate of Tregs at sites of inflammation, particularly in the context of autoimmune diabetes.

Credentials

Faculty Appointments

Education

1988
BS | Bristol University, UK
Cellular Pathology

1992
PhD | Oxford University, UK
Immunology

Awards

2013
Deans Professorship
Sponsor: URMC

2011
Basic Science Mentoring Award
Location: URMC

2010
Graduate Student Society Faculty Award
Location: University of Rochester Medical School

2007
Mary Jane Kugel Award
Sponsor: Juvenile Diabetes Research Foundation

2006 - 2007
Discovery Concept Fund
Sponsor: Johnson and Johnson

2000 - 2004
HHMI Junior Faculty Start-up Award
Sponsor: Hughes
Location: University of Rochester

2000
Pew Scholars Nominee
Location: University of Rochester

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Publications

Journal Articles

10/18/2016
Meli AP, Fontés G, Avery DT, Leddon SA, Tam M, Elliot M, Ballesteros-Tato A, Miller J, Stevenson MM, Fowell DJ, Tangye SG, King IL. "The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance." Immunity.. 2016 Oct 18; 45(4):831-846.

9/15/2016
Billroth-MacLurg AC, Ford J, Rosenberg A, Miller J, Fowell DJ. "Regulatory T Cell Numbers in Inflamed Skin Are Controlled by Local Inflammatory Cues That Upregulate CD25 and Facilitate Antigen-Driven Local Proliferation." The Journal of immunology : official journal of the American Association of Immunologists.. 2016 Sep 15; 197(6):2208-18. Epub 2016 Aug 10.

9/2016
Lambert Emo K, Hyun YM, Reilly E, Barilla C, Gerber S, Fowell D, Kim M, Topham DJ. "Live Imaging of Influenza Infection of the Trachea Reveals Dynamic Regulation of CD8+ T Cell Motility by Antigen." PLoS pathogens.. 2016 Sep 0; 12(9):e1005881. Epub 2016 Sep 19.

Books & Chapters

2001
Chapter Title: The Th1/Th2 Paradigm in infections
Book Title: Immunology of Infectious Disease
Author List: Mosmann, T. & Fowell, DJ
Edited By: Kaufmann, Sher & Ahmed
Published By: ASM press2001

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