Deborah J. Fowell, Ph.D.

Deborah J. Fowell, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 609
Rochester, NY 14642

Office: (585) 273-3680
Lab: (585) 273-2902
Administrative: (585) 273-1400
Fax: (585) 273-2452

Research Bio

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.

Awards & Honors (National)

Mary Jane Kugel Award | Juvenile Diabetes Research Foundation 2007
HHMI Junior Faculty Start-up Award | University of Rochester 2000 - 2004

Awards & Honors (Local)

Basic Science Mentoring Award | URMC 2011
Graduate Student Society Faculty Award | University of Rochester Medical School 2010
Discovery Concept Fund | Johnson and Johnson 2006 - 2007
Pew Scholars Nominee | University of Rochester 2000

Recent Journal Articles

Showing the 5 most recent journal articles. 47 available »

2012 Jul 2
Hyun YM, Sumagin R, Sarangi PP, Lomakina E, Overstreet MG, Baker CM, Fowell DJ, Waugh RE, Sarelius IH, Kim M. "Uropod elongation is a common final step in leukocyte extravasation through inflamed vessels." The Journal of experimental medicine.. 2012 Jul 2; 209(7):1349-62. Epub 2012 Jun 18.
2012 Feb 1
Huang YH, Sojka DK, Fowell DJ. "Cutting edge: Regulatory T cells selectively attenuate, not terminate, T cell signaling by disrupting NF-?B nuclear accumulation in CD4 T cells." The Journal of immunology : official journal of the American Association of Immunologists.. 2012 Feb 1; 188(3):947-51. Epub 2012 Jan 06.
2012
Mock DJ, Hollenbaugh JA, Daddacha W, Overstreet MG, Lazarski CA, Fowell DJ, Kim B. "Leishmania induces survival, proliferation and elevated cellular dNTP levels in human monocytes promoting acceleration of HIV co-infection." PLoS pathogens. 2012 8(4):e1002635. Epub 2012 Apr 05.
2011 Nov 8
Sojka DK, Fowell DJ. "Regulatory T cells inhibit acute IFN-? synthesis without blocking T-helper cell type 1 (Th1) differentiation via a compartmentalized requirement for IL-10." Proceedings of the National Academy of Sciences of the United States of America.. 2011 Nov 8; 108(45):18336-41. Epub 2011 Oct 24.
2011 Oct 4
Singleton KL, Gosh M, Dandekar RD, Au-Yeung BB, Ksionda O, Tybulewicz VL, Altman A, Fowell DJ, Wülfing C. "Itk controls the spatiotemporal organization of T cell activation." Science signaling. 2011 Oct 4; 4(193):ra66.

Current Appointments

Dean's Associate Professorship - Department of Microbiology and Immunology, Center for Vaccine Biology and Immunology (SMD)
Associate Professor - Department of Microbiology and Immunology, Center for Vaccine Biology and Immunology (SMD) - Primary

Education

PhD | Immunology | Oxford University, UK1992
BS | Cellular Pathology | Bristol University, UK1988

Post-Doctoral Training & Residency

UCSF, San Francisco, CA. Infectious Disease Division (Mentor: Richard Locksley) 1998
Oxford University, UK. (Mentor: Don Mason) 1994