Donna Farber, Ph.D.
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.
For more information, visit our lab website.
- Miron, M., Kumar, B.V., Meng, W., Granot, T., Carpenter, D.J., Senda, T., Chen, D., Rosenfeld, A.M., Zhang, B., Lerner, H., Friedman, A.L., Hershberg, U., Shen, Y., Rahman, A., Luning Prak, E.T. and Farber, D.L. (2018) Human lymph nodes maintain TCF-1(hi) memory T cells with high functional potential and clonal diversity throughout life. J. Immunol. 201: 2132-2140.
- Fu, J., Zuber, J., Martinez, M., Shonts, B., Obradovic, A., Wang, H., Lau, S.P., Xia, A., Waffarn, E.E., Frangaj, K., Savage, T.M., Simpson, M.T., Yang, S., Guo, X.V., Miron, M., Senda, T., Rogers, K., Rahman, A., Ho, S.H., Shen, Y., Griesemer, A., Farber, D.L., Kato, T. and Sykes, M. (2018) Human intestinal allografts contain functional hematopoietic stem and progenitor cells that are maintained by a circulating pool. Cell Stem Cell https://doi.org/10.1016/j.stem.2018.11.007 [epub ahead of print]
- Kumar, B.V., Connors, T.J. and Farber, D.L. (2018) Human T cell development, localization, and function throughout life. Immunity 48: 202-213.
- Carpenter, D.J., Granot, T., Matsuoka, N., Senda, T., Kumar, B.V., Thome, J.J.C., Gordon, C.L., Miron, M., Weiner, J., Connors, T., Lerner, H., Friedman, A., Kato, T., Griesemer, A.D. and Farber, D.L. (2018) Human immunology studies using organ donors: Impact of clinical variations on immune parameters in tissues and circulation. Am. J. Transplant. 18: 74-88.
- Klose, C.S.N., Mahlakoiv, T., Moeller, J.B., Rankin, L.C., Flamar, A.L., Kabata, H., Monticelli, L.A., Moriyama, S., Putzel, G.G., Rakhilin, N., Shen, X., Kostenis, E., Konig, G.M., Senda, T., Carpenter, D., Farber, D.L. and Artis, D. (2017) The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation. Nature 549: 282-286.
- Kumar, B.V., Ma, W., Miron, M., Granot, T., Guyer, R.S., Carpenter, D.J., Senda, T., Sun, X., Ho, S.H., Lerner, H., Friedman, A.L., Shen, Y. and Farber, D.L. (2017) human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites. Cell Rep. 20: 2921-2934.
- Nish, S.A., Zens, K.D., Kratchmarov, R., Lin, W.W., Adams, W.C., Chen, Y.H., Yen, B., Rothman, N.J., Bhandoola, A., Xue, H.H., Farber, D.L. and Reiner, S.L. (2017) CD4+ T cell effector commitment coupled to self-renewal by asymmetric cell divisions. J. Exp. Med. 214: 39-47.
- Kumar, B.V., Ma, W. Miron, M., Granot, T., Guyer, R.S., Carpenter, D.J., Senda, T., Ho, S.-H., Lerner, H., Friedman, A.L., Shen, Y., and Farber, D.L. (2017) Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites. Cell Reports 20: 2921-2934.
- Zens, K.D., Chen, J.-K., Guyer, R.S., Wu, F.L., Cvetkovski, F., Miron, M. and Farber, D.L. (2017) Reduced generation of lung-tissue resident memory T cells during infancy. J. Exp. Med. 214: 2915-2932.
- Meng, W., Zhang, B., Schwartz, G.W., Rosenfeld, A.M., Ren, D., Thome, J.J.C., Carpenter, D., Matsuoka, N., Granot, T., Farber, D.L., Shlomchik, M.J., Hershberg, U. and Luning Prak, N.T. (2017) An atlas of B cell clonal distribution in the human body. Nature Biotech. 35: 879-884.
- Granot, T., Senda, T., Carpenter, D., Matsuoka, N., Weiner, J., Gordon, C.L., Miron, M., Kumar, B.V., Griesemer, A., Ho, S.-H., Lerner, H., Thome, J.J.C., Connors, T., Reizis, B., and Farber, D.L. (2017) Dendritic cells display subset and tissue-specific maturation dynamics over human life. Immunity 46: 504-515.
- Gordon, C.L., Miron, M., Thome, J.J.C., Matsuoka, N., Weiner, J., Rak, M., Igarashi, S., Granot, T., Lerner, H., Goodrum, F. and Farber, D.L. (2017) Tissue-reservoirs of T cell immunity in persistent human CMV infection. J. Exp. Med. 214: 651-667.
- Thome, J.J.C., Grinshpun, B., Kumar, B.V., Kubota, M., Ohmura, Y., Lerner, H., Sempowski, G.D., Shen, Y. and Farber, D.L. (2016) Longterm maintenance of human naive T cells through in situ homeostasis in lymphoid tissue sites. Sci. Immunol. 1: eaah6506.
- Zens, K.D., Chen, J.-K. and Farber, D.L. (2016) Vaccine-generated lung tissue-resident memory T cells provide heterosubtypic protection to influenza virus infection. J. Clin. Invest. Insight 1: e85832. doi:10.1172/jci.insight.85832.
- Connors, T.J., Ravindranath,T.M., Bickham,K.L., Gordon,C.L., Zhang, F., Levin,B., Baird, J.S. and Farber, D.L. (2016) Airway CD8 T-cells are associated with lung injury during infant viral respiratory tract infection. Amer. J. Resp. Cell and Mol. Biol. 54: 822-830.
- Thome, J.J., Bickham, K.L., Ohmura, Y., Kubota, M., Matsuoka, N., Gordon, C., Granot, T., Griesemer, A., Lerner, H., Kato, T. and Farber, D.L. (2016) Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues. Nature Med. 22: 72-77.
- Yu, M., Owens, D.M., Ghosh, S. and Farber, D.L. (2015) Conditional PDK1 ablation promotes epidermal and T-cell-mediated dysfunctions leading to inflammatory skin disease. J. Invest. Dermatol. 135: 2688-2696.
- Brestoff, J.R., Kim, B.S., Saenz, S.A., Stine, R.R., Monticelli, L.A., Sonnenberg, G.F., Thome, J.J., Farber, D.L., Lutfy, K., Seale, P. and Artis, D. (2015) Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature 519: 242-246.
- Thome, J.J. and Farber, D.L. (2015) Emerging concepts in tissue-resident T cells: lessons from humans. Trends Immunol. 36: 428-435.
- 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.
- 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 519: 242-246.
- 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: 814-828. PMCID: PMC4243051
- Farber, D.L., Yudanin, N.A. and Restifo, N.P. (2014) Human memory T cells: generation, compartmentalization and homeostasis. Nature Rev. Immunol. 14: 24-35.
- Turner, D.L., Bickham, K.L., Thome, J.J., Kim, C.Y., D'Ovidio, F., Wherry, E.J. and Farber, D.L. (2013) Lung resident niches for the generation and maintenance of tissue-resident memory T cells. Mucosal Immunol. 7: 501-510
- Sathaliyawala, T., Kubota, M., Yudanin, N., Turner, D., Camp, P., Thome, J.J.C., Bickham, K.L., Lerner, H., Goldstein, M., Sykes, M., Kato, T. and Farber, D.L. (2013). Distribution and compartmentalization of circulating and tissue-resident memory subsets. Immunity 38: 187-197. PMCID: PMC3557604.
- Teijaro, J.R., Turner, D., Nam, Q., Wherry, E.J., LeFrancois, 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. PMCID: PMC3221837.
- 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. PMCID: PMC3320042.
- 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. PMCID: PMC2937635.
- Bushar, N.D., Schmidt, M., Corbo, E., 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. Natl. Acad. USA 107: 827-31. PMCID: PMC2818906.