Professor Donna Farber Phone: 212-305-6030 Lab Phone: 212-342-0599 Fax: 212-305-4038 Email: df2396@columbia.edu Website: farberlab.org

Professor Donna Farber
Phone: 212-305-6030
Lab Phone: 212-342-0599
Fax: 212-305-4038
Email: df2396@columbia.edu
Website: farberlab.org

Donna Farber, Ph.D.

George H. Humphreys, II Professor of Surgical Sciences (in Surgery), Chief, Division of Surgical Sciences and Professor of Microbiology & Immunology
Fellow, American Association for the Advancement of Science
Ph.D., University of California, Santa Barbara

Immunological memory and memory T cells

Research
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.

Professor Farber is a Distinguished Fellow of the American Association of Immunologists.

 

Selected Publications

  1. Matsumoto, R., Gray, J., Rybkina, K., Oppenheimer, H., Levy, L. Friedman, L.M., Khamaisi, M., Meng, W., Rosenfeld, A.M., Guyer, R.S., Bradley, M.C., Chen, D., Atkinson, M.A., Brusko, T.M., Brusko, M., Connors, T.J., Luning Prak, E.T., Hershberg, U., Sims, P.A., Hertz, T., and Farber, D.L. (2023) Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity. Nature Immunol. 24: 1370-1381. PMC10529876.

  2. Connors, T.J., Szabo, P.A., Matsumoto, R., Guyer, R., Levitin, H.M., Verma, S., Thapa, P., Dogra, P., Poon, M.M.L., Gray, J., Rybkina, K., Bradley, M.C., Idzikowski, E., McNichols, J., Kubota, M., Pethe, K., Yates, A.J, Brusko, M., Brusko, T.M., Sims, P.A., and Farber, D.L. (2023) Site-specific development and progressive maturation of human tissue resident memory T cells over infancy and childhood. Immunity 56: 1894-1909. PMC10527943.

  3. Poon, M. M. L., Caron, D. P., Wang, Z., Wells, S. B., Chen, D., Meng, W., Szabo, P. A., Lam, N., Kubota, M., Matsumoto, R., Rahman, A., Luning Prak, E. T., Shen, Y., Sims, P. A. and Farber, D. L. (2023) Tissue adaptation and clonal segregation of human memory T cells in barrier sites. Nature Immunology 24: 309–319. https://doi.org/10.1038/s41590-022-01395-9

  4. Ural, B.B., Caron, D.P., Dogra, P., Wells, S.B., Szabo, P.A., Granot, T., Senda, T., Poon, M.M.L., Lam, N., Thapa, P., Lee, Y., Kubota, M., Matsumoto, R. and Farber, D.L. (2022) Inhaled particulate accumulation with age impairs immune function and architecture in human lung lymph nodes. Nature Medicine 28: 2622–2632. https://doi.org/10.1038/s41591-022-02073-x

  5. Chait, M., Mine, Y., Shakil, S., Ku, A., Dogra, P., Connors, T.J., Szabo, P.A., Gray, J.I,. Wells, S.B., Kubota, M., Matsumoto, R., Poon, M.M.L., Snyder, M.E., Baldwin, M.R., Sims, P.A., Saqi, A., Farber D.L. and Weisberg, S.P. (2022) Immune and epithelial determinants of age-related risk and alveolar injury in fatal COVID-19. JCI Insight 7: e157608. https://doi.org/10.1172/jci.insight.157608

  6. Weisel, N.M., Joachim, S., Smita, S., Callahan, D., Elsner, R., Conter, L., Chikina, M., Farber, D.L., Weisel, F. and Shlomchik, M.J. (2022) Surface phenotypes of naïve and memory B cells in mouse and human tissues. Nature Immunology 23: 135-145.

  7. Thapa P., Guyer R.S., Yang A.Y., Parks C.A., Brusko T.M., Brusko M., Connors T.J. and Farber D.L. (2021) Infant T cells are developmentally adapted for robust lung immune responses through enhanced T cell receptor signaling. Science Immunology 6: eabj0789.

  8. Poon M.L., Rybkina K., Kato Y., Kubota M., Matsumoto R., Bloom N.I., Zhang Z., Hastie K.M., Grifoni A., Weiskopf D., Wells S.B., Ural B.B., Lam N., Szabo P.A., Dogra P., Lee Y.S., Gray J.I., Bradley M.C., Brusko M.A., Brusko T.M., Saphire E.O., Connors T.J., Sette A., Crotty S. and Farber D.L. (2021) SARS-CoV-2 infection generates tissue-localized immunological memory in humans. Science Immunology 6: eabl9105.

  9. Poon, M.M.L., Byington, E., Meng, W., Kubota, M., Matsumoto, R., Grifoni, A., Weiskopf, D., Dogra, P., Lam, N., Szabo, P. A., Ural, B. B., Wells, S. B., Rosenfeld, A.M., Brusko,M.A., Brusko, T.M., Connors, T.J., Sette, A., Sims, P.A., Luning Prak, E.T., Shen, Y. and Farber, D.L. (2021) Heterogeneity of human anti-viral immunity shaped by virus, tissue, age, and sex. Cell Reports 37: 110071.

  10. Miron, M., Meng, W., Rosenfeld, A.M., Dvorkin, S., Poon, M.M.L., Lam, N., Kumar, B.V., Louzoun, Y., Luning Prak, E.T. and Farber, D.L. (2021) Maintenance of the human memory T cell repertoire by subset and tissue site. Genome Medicine 13: 100.

  11. Weisberg, S.P., Ural, B. B. and Farber, D.L. (2021) Tissue specific immunity for a changing world. Cell 184: 1517-1529. [Special issue on “Biology for an uncertain future”]

  12. Szabo, P.A., Dogra, P., Gray, J.I., Wells, S.B., Connors, T.J., Weisberg, S.P., Krupska, I., Matsumoto, R., Poon, M.M.L., Idzikowski, E., Morris, S.E., Pasin, C., Yates, A.J., Ku, A., Chait, M., Davis-Porada, J., Zhou, J., Steinle, M., Mackay, S., Saqi, A., Baldwin, M.R., Sims, P.A. and Farber, D.L. (2021) Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19. Immunity 54: 797–814.e6.

  13. Okla, K., Farber, D.L. and Zhou, W. (2021) Tissue-resident memory T cells in tumor immunity and immunotherapy. J. Exp. Med. 218: e20201605.

  14. Paik, D. and Farber, D.L. (2021) Influenza infection fortifies local lymph nodes to promote lung resident heterosubtypic immunity. J. Exp. Med. 218: e20200218. [Highlighted in JEM Immunology collection 2021: https://rupress.org/jem/collection/19938/JEM-Immunology-Collection-2021]

  15. Weisberg, S.P., Connors, T.J., Zhu, Y., Baldwin, M.R., Lin, W.-H, Wontakal, S., Szabo, P.A., Wells, S.B., Dogra, P., Gray, J., Idzikowski, E., Stelitano, D., Bovier, F.T., Davis-Porada, J., Matsumoto, R., Poon, M.M.L., Chait, M., Mathieu, C., Horvat, B., Decimo, D., Hudson, K.E., Dei Zotti, F., Bitan, Z.C., La Carpia, F., Ferrara, S.A., Mace, E., Milner, J., Moscona, A., Hod, E., Porotto, M. and Farber, D.L. (2021) Distinct Antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum. Nature Immunology 22: 25-31. [Highlighted in The New York Times https://www.nytimes.com/2020/11/05/health/covid-children-antibodies.html and multiple lay press outlets.]

  16. Yun, T.J., Igarashi, S., Pereira, M.R., Zorn, E., Goodrum, F., Rahman, A., Sims, P.A., Farber, D.L. and Reizis, B. (2021) Human plasmacytoid dendritic cells recognize cytomegalovirus-infected cells and mount a prolonged interferon-biased response. Science Immunology 6: eabc7302.

  17. Dogra, P., Rancan, C., Ma, W., Toth, M., Senda, T., Carpenter, D., Thapa, P., Szabo, P., Shen,Y., Fong, L., Lanier, L. and Farber, D.L. (2020) Tissue determinants of human NK development, function and residence. Cell 180: 749-763.

  18. Weisberg, S.P., Carpenter, D.J., Chait, M., Dogra, P., Gartrell-Corrado, R.D., Chen, A.X., Campbell, S., Liu, W., Saraf, P., Snyder, M.E., Kubota, M., Danzl, N.M., Schrope, B.A., Rabadan, R., Saenger, Y., Chen, X. and Farber, D.L. (2019) Tissue-resident memory T cells mediate immune homeostasis in the human pancreas through the PD-1/PD-L1 pathway. Cell Rep. 29: 3916-3932.e5. PMCID: PMC6939378.

  19. Snyder, M. E., Finalyson, M. O., Connors, T.J., Senda, T., Carpenter, D., Bush, E., Marboe, C., Benvenuto, L., Shah, L., Robbins, H., Hook, J.L., Sykes, M., D'Ovidio, F, Bacchetta, M., Sonett, J.R., Lederer, D.J., Arcasoy, S., Sims, P.A. and Farber, D.L. (2019) Generation and persistence of human tissue-resident memory T cells in lung transplantation. Science Immunology 4: eaav5581. PMCID: PMC6435356.

  20. 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. (2019) Human intestinal allografts contain functional hematopoietic stem and progenitor cells that are maintained by a circulating pool. Cell Stem Cell 24: 227-239.

  21. 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.

  22. Kumar, B.V., Kratchmarov, R., Miron, M., Carpenter, D.J., Senda, T., Lerner, H., Friedman, A., Reiner, S.L., and Farber, D.L. (2018) Functional heterogeneity of human tissue-resident memory T cells based on dye efflux capacities. JCI Insight 3: e123568.

  23. Kumar, B.V., Connors, T.J. and Farber, D.L. (2018) Human T cell development, localization, and function throughout life. Immunity 48: 202-213.

  24. 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.

  25. 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.

  26. 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 Reports 20: 2921-2934.

  27. 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.

  28. 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.

  29. 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.

  30. 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.

  31. 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.

  32. 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.

  33. 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. Science Immunology 1: eaah6506.

  34. 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. https://doi.org/10.1172/jci.insight.85832

  35. 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.

  36. 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 Medicine 22: 72-77.

  37. Connors, T.J., Ravindranath, T.M., Bickham, K.L., Gordon, C.L., Zhang, F., Levin, B., Baird, J.S. and Farber, D.L. (2015) Airway CD8 T-cells are associated with lung injury during infant viral respiratory tract infection. Am. J. Respir. Cell. Mol. Biol. 54: 822-830. https://doi.org/10.1165/rcmb.2015-0297OC

  38. 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.

  39. 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.

  40. Thome, J.J. and Farber, D.L. (2015) Emerging concepts in tissue-resident T cells: lessons from humans. Trends Immunol. 36: 428-435.

  41. 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.

  42. 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.

  43. 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

  44. 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.

  45. 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

  46. 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.

  47. 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. PMCID: PMC3624369.

  48. Sonnenberg, G.F., Monticelli, L.A., Alenghat, T., Fung, T.C., Hutnick, N.A., Kunisawa, J., Shibata, N., Grunberg, S., Sinha, R., Zahm, A.M., Tardif, M.R., Sathaliyawala, T., Kubota, M., Farber, D.L., Collman, R.G., Shaked, A., Fouser, L.A., Weiner, D.B., Tessier, P.A., Friedman, J.R., Kiyono, H., Bushman, F.D., Chang, K.M. and Artis, D. (2012) Innate lymphoid cells orchestrate anatomical containment of lymphoid-resident commensal bacteria and prevent systemic immune activation. Science 336: 1321-5. PMCID: 3659421.

  49. 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.

  50. 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.

  51. 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. PMCID: PMC3131107.

  52. 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.

  53. 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.

  54. Teijaro, J.R., Njau, M.P., Verhoeven, D., Chandran, S., Nadler, S.G., Hasday, J. and Farber, D.L. (2009). Costimulation modulation uncouples protection from immunopathology in memory T cell responses to influenza virus. J. Immunol. 182: 6834-43. PMID: 19454679.