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 Description:

     Research in the laboratory is focused on immunological memory and specifically on memory T cells as essential mediators of protective immunity. While it was previously thought that memory T cells mediate their protective responses through rapid migration and surveillance through tissues, it is now become clear that localization and establishment of non-circulating memory T cells resident in tissue sites is integral to immune protection. We are incorporating fundamental studies on mouse models with novel translational approaches on human samples to investigate tissue immune responses. We have identified a new subset of non-circulating tissue-resident memory T cells (TRM) in the lung that mediate optimal protective immunity in a mouse model of influenza infection. Current studies into mechanisms for how memory T cells become targeted to and maintained in the lung use total transcriptome profiling and bioinformatics approaches. We have identified novel roles for specific integrins and inflammatory mediators in this process, and are studying the signaling pathways involved in resident memory T cell generation and functional recall.
     For our translational studies, we have established a unique collaboration and research protocol with the organ procurement organization for the New York Metropolitan area (LiveOnNY ; http://www.donatelifeny.org/) and transplant surgeons at New York Presbyterian (NYP) where we obtain multiple lymphoid and mucosal tissues from research-consented human organ donors. These studies are part of an NIH-funded Program on “Tissue compartmentalization of human lymphocytes”, involving immunologists, molecular biologists and computational biologists in five institutions to study human adaptive and innate lymphocyte compartmentalization and maintenance in human tissues throughout the human lifespan. Additionally, because memory T cells are critically important to generate in vaccines, we have ongoing studies on infant immunity, to investigate how protective responses can be established in babies who are most susceptible to infection and immune pathologies. These infant studies involve both mouse models and also sampling of site-specific responses in human infants intubated due to virus infection in collaboration with clinicians in the Pediatric Critical care Division at Morgan Stanley/NYP.

Laboratory Personnel:
Renee McKell, M.S., Laboratory Manager
Damian Turner, Ph.D., Postdoctoral Fellow
Minjun Yu, Ph.D., Postdoctoral Fellow
Tomer Granot, Ph.D., Postdoctoral Research Scientist
Matsuoka Nobuhide, M.D., Procurement Surgeon
Claire Gordon, M.D., Associate Research Scientist
Naomi Yudanin, M.S., Ph.D. Candidate
Joseph Thome, M.S., Ph.D. Candidate
Kyra Zens, M.S., Ph.D. Candidate
Jun Kui Chen, B.S., Ph.D. Candidate
Filip Cvetkovski, B.S., Graduate Student
Thomas Connors, M.D., Pediatric Critical Care Fellow

Selected Publications (last 4 years)

Thome, J.J.C., Yudanin, N.A., Ohmura, Y., Kubota, M., Grinshpun, B., Sathaliyawala, T., Kato, T., Lerner, H., Shen, Y. and Farber, D.L. (2014) Spatial map of human T cell compartmentalization and maintenance over decades of life. Cell. 159:814-28. PMCID:PMC4243051

Brestoff,J.R., Kim,B.S., Saenz,S.A., Stine,R.R., Monticelli,L.A., Sonnenberg,G.A., Thome,J.J.T., Farber,D.L., Lutfy,K., Seale, P., and Artis, D. (2014) Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit diet-induced obesity. Nature, doi: 10.1038/nature14115. [Epub ahead of print]

Zens, K.D. and Farber, D.L. (2015) Memory CD4 T cell responses to influenza virus. Current Topics in Microbiology and Immunology. 386:399-421.

Farber, D.L. , Yudanin, N.A. and Restifio, N.P. (2014) Human Memory T cells: generation, compartmentalization and homeostasis. Nature Reviews Immunology.14:24-35. (featured on cover) PMCID:PMC4032067

Turner, D.L., Bickham, K.L., Thome, J.J.T., Kim, C., D’Ovidio, F., Wherry, E.J. and Farber, D.L. (2014) Lung resident niches for the generation and maintenance of influenza-specific memory T cells. Mucosal Immunology. 7:501-10.

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.
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.)

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.

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., 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)

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.

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