Dr. Donna Farber's Research

Memory CD4 T Cells and Immune Responses To Influenza Virus | Mapping The Human Immune ResponseSignaling Pathways For Memory CD4 T Cell Recall And Homeostasis

Research Interests:

The focus of Dr. Farber’s research is on immunological memory, and in particular on memory T cells which direct and coordinate anamnestic immune responses to pathogens and can mediate immunopathology in autoimmune disease and in transplantation. Memory T cells are generated following an initial encounter with antigen and can persist in multiple lymphoid and non-lymphoid peripheral tissue sites. We have recently identified that lungs contain a resident population of memory T cells that are retained in the lung and mediate optimal protective responses to influenza virus. We are investigating how these tissue resident memory T cells are generated and retained in mucosal sites in mouse virus infection models, and how pancreas-homing autoreactive memory T cells are generated and maintained in a mouse model for Type I diabetes. Biochemical and molecular approaches are also being taken to elucidate mechanisms controlling the rapid recall response of memory T cells and their homeostasis and maintenance in mouse models with conditional deletion of key signal transduction intermediates. We have recently begun translational studies on human memory T cells, with a focus on characterizing tissue-specific immune responses in multiple lymphoid and non-lymphoid human tissue obtained from organ donors in collaboration with the New York organ donor network. Other translational studies in progress include analyses of T cell homeostasis and function in human transplant recipients and in Type I diabetes.

Lab members:

Damian Turner, PhD, Postdoctoral Fellow
Kara Bickham, MD, Associate Research Scientist
Minjin Yu, PhD, Postdoctoral Fellow
Renee McKell, Laboratory Manager
Naomi Yudanin, Graduate Student
Joseph Thome, Graduate Student
Jun Kui Chen, Graduate Student
Claire Gordon, Fellow in Transplant Infectious Diseases
Kyra Zens, Graduate Student
Thomas Connors, Fellow in Pediatric Critical Care Medicine

 

Selected Publications:

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Bushar, N.D., Corbo, E., Schmidt, M., Maltzman, J.S. and Farber, D.L.  (2010) Ablation of SLP-76

signaling after T cell priming generates memory CD4 T cells impaired in steady-state and cytokine-driven homeostasis.  Proc. Nat’l. Acad. Sci. U.S.A. 107:827-831.

Teijaro, J.R., Verhoeven, D., Page, C.A. and Farber, D.L. (2010) Memory CD4 T cells Direct Protective Responses to Influenza Virus in the Lung through Helper-independent Mechanisms. J. Virol. 84:9217-26. (selected for editors’ spotlight feature)

Lai, W., Yu, M., Okoye, F.I., Keegan, A.D. and Farber, D.L. (2011) Transcriptional control of rapid recall in Memory CD4 T cells.  J. Immunol.  187: 133-40.

Teijaro, J.R., Turner, D., Nam, Q., Wherry, E.J., LeFrançois, L. and Farber, D.L. (2011) Cutting Edge: Tissue-retentive lung memory CD4 T cells mediate optimal protective responses to influenza. J. Immunol. 187:5510-14.

Monticelli, L.A., Sonnenberg, G.F., Abt, M. C., Alenghat, T., Ziegler, G.K., Doering, T.A., Angelosanto, J.M., Laidlaw, B.J., Yang, C.Y., Sathaliyawala, T., Kubota, M., Turner, D., Diamond, J.M., Goldrath, A.W., Farber, D.L., Collman, R.G., Wherry, E.J., and Artis, D. (2011) Innate lymphoid cells promote lung tissue homeostasis following acute influenza virus infection.  Nature Immunol. 12: 1045-54.

Sathaliyawala, T., Kubota, M., Yudanin, N., Turner, D., Camp, P., Thome, J.C., Bickham, K.L., Lerner, H., Goldstein, M., Sykes, M., Kato, T and Farber, D.L.  (2013) Distribution and compartmentalization of human circulating and tissue-resident memory T cells.  Immunity. 38: 187-197.  (Also see preview article in same issue by Neuenhahn and Busch, D.H., “Whole body anatomy of human T cells”. Immunity. 38:10-12.)

Turner, D.L., Bickham, K.L., Farber, D.L. and Lefrancois, L. (2013) Splenic priming of virus-specific CD8 T cells following influenza infection.  J. Virol. 87:4496-506.

Turner, D.L., Bickham, K.L., Thome, J.J.T., Kim, C., D’Ovidio, F., Wherry, E.J. and Farber, D.L. (2013) Lung resident niches for the generation and maintenance of influenza-specific memory T cells. Mucosal Immunology. Online before print PMID:24064670.

Farber, D.L. , Yudanin, N.A. and Restifio, N.P. (2013) Human Memory T cells: generation, compartmentalization and homeostasis.  Nature Reviews Immunology. In Press.

Turner, D.L., Gordon, C.L. and Farber, D.L. (2014) Tissue resident T cells, in situ immunity and transplantation.  Immunol. Reviews. In Press.