Donna L. Farber, PhD

Profile Headshot

Overview

Academic Appointments

  • George H. Humphreys, II Professor of Surgical Sciences (in Surgery)
  • Professor of Microbiology & Immunology

Administrative Titles

  • Division Chief, Surgical Sciences
  • Principal Investigator, Columbia Center for Translational Immunology

Credentials & Experience

Education & Training

  • BS, Microbiology, University of Michigan, Ann Arbor
  • PhD, Biochemistry and Molecular Biology, University Of California
  • Fellowship: Pasteur Institute (Institut Pasteur)
  • Fellowship: Yale University School of Medicine

Research

Immune memory and protective immunity Influenza immune responses Transplantation immunology Autoimmunity

Research in our 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.

Grants

VACCINE INDUCED IMMUNITY IN THE YOUNG AND AGED (Federal Gov)

May 1 2019 - Apr 30 2024

TISSUE COMPARTMENTALIZATION OF HUMAN LYMPHOCYTES (Federal Gov)

Jun 25 2018 - May 31 2023

IMMUNOBIOLOGY AND ALVEOLAR PHYSIOLOGY OF THE AGING LUNG (Federal Gov)

Jan 1 2019 - Dec 31 2022

DEVELOPMENT OF LUNG T CELL RESPONSES IN INFANT RESPIRATORY IMMUNITY (Federal Gov)

Aug 1 2017 - Jul 31 2022

AN INTEGRATED MAP OF THE IMMUNE SYSTEM IN HUMANS ACROSS TISSUES AND AGES (Private)

Jul 1 2019 - Jun 30 2022

HUMAN ANTI-VIRAL IMMUNE RESPONSES IN TISSUES AND CIRCULATION (Federal Gov)

Jan 1 2017 - Dec 31 2021

THE IMPACT OF T CELL CHIMERISM ON REJECTION FOLLOWING LUNG TRANSPLANTATION (Private)

Jul 1 2018 - Jun 30 2021

THE ROLE OF GAMMA-DELTA T CELLS IN HUMAN EARLY LIFE IMMUNITY (Private)

Dec 1 2019 - May 31 2021

IMPACT OF TISSUE LOCATION ON ANTITUMOR ACTIVITY OF HUMAN NK CELLS (Private)

Jan 1 2018 - Dec 31 2020

ANTIGEN-INDEPENDENT ANTIBODY DIVERSIFICATION IN GALT OF YOUNG CHILDREN (Federal Gov)

Jun 1 2018 - May 31 2020

DISSECTING HUMAN TISSUE RESIDENT MEMORY T CELL HETEROGENEITY USING SINGLE CELL PROTEOGENOMICS (Private)

Feb 1 2019 - Jan 31 2020

LUNG RESIDENT NICHES FOR MEMORY CD4 T CELLS (Federal Gov)

Dec 15 2014 - Nov 30 2019

MECHANISMS OF ANESTHETIC EFFECTS ON TACHYKININ INDUCED AIRWAY TONE (Federal Gov)

Sep 20 2015 - Aug 31 2019

TISSUE IMMUNE RESPONSES IN THE HUMAN PANCREAS (Private)

Aug 15 2017 - Aug 14 2019

ROLE OF TISSUE RESIDENT MEMORY T CELLS IN BOTH ACUTE AND CHRONIC REJECTION FOLLOWING LUNG TRANSPLANTATION (Private)

Jul 1 2018 - Jun 30 2019

CANCER CENTER SUPPORT GRANT (Federal Gov)

Jul 1 2014 - Jun 30 2019

DNA ELEMENTS UNDERLYING CELIAC AND CROHN S SUSCEPTIBILITY (Federal Gov)

Jun 1 2018 - May 31 2019

HUMAN ATLAS OF NEONATAL DEVELOPMENT AND EARLY-LIFE IMMUNITY (Private)

Apr 1 2018 - Mar 31 2019

OBESITY, INFLAMMATION AND LUNG INJURY AFTER LUNG TRANSPLANTATION (Federal Gov)

May 23 2013 - Mar 31 2018

THERAPEUTIC TARGETING OF INTRINSIC T CELL SUPPRESSION DURING ANTI-TUMOR IMMUNITY (Private)

Jul 1 2015 - Jun 30 2017

TRANSLATIONAL AND NAIVE CD4 T CELLS AND B CELLS IN INFANT VACCINE RESPONSES (Federal Gov)

Sep 1 2015 - Mar 31 2017

LONGEVITY AND TURNOVER OF HUMAN NAIVE T CELLS IN LYMPHOID TISSUE (Federal Gov)

Sep 16 2013 - Sep 15 2016

A NOVEL MOUSE MODEL FOR IMMUNE-MEDIATED SKIN FIBROSIS IN SCLERODERMA (Federal Gov)

Jul 1 2013 - Mar 31 2016

A NOVEL MOUSE MODEL FOR IMMUNE-MEDIATED SKIN FIBROSIS (Private)

Jul 1 2013 - Jun 30 2015

RESIDENT AND RECUITED MEMORY CD3 T CELLS IN (Private)

Jul 1 2012 - Jun 30 2015

EQUIPMENT APPLICATION: CRYOSTAT ROLE OF RESPIRATORY INNATE LIKE LYMPHOCYTES/NUOCYTES DURING DIVERSE VIRAL INFECTIONS (Federal Gov)

May 1 2013 - Apr 30 2014

PROBING MECHANISMS FOR LUNG HOMING OF MEMORY CD4 T CELLS BY AN SHRNA SCREENING APPROACH (Federal Gov)

Sep 1 2012 - Apr 30 2014

SHAPING ANTIVIRAL IMMUNITY BY THE INFLAMMATORY,REGULATORY AND TISSUE ENVIRONMENT (Federal Gov)

Jul 1 2010 - Apr 30 2014

MUCOSAL MEMORY T CELLS AT THE VANGUARD OF HUMAN HOST DEFENSE (Federal Gov)

Sep 27 2010 - Aug 31 2012

SHAPING ANTIVIRAL IMMUNITY BY THE INFLAMMATOR, REGULARTORY A ND ISSUE ENVIRONMENT (Federal Gov)

May 1 2011 - Jul 31 2012

SHAPING ANTIVIRAL IMMUNITY BY THE INFLAMMATORY, REGULATORY A ND ISSUE ENVIRONMENT (Federal Gov)

May 1 2011 - Jul 31 2012

NEW MODEL TO HELP INVESTIGATE FACTORS THAT SHAPE ANTIVIRAL I MMUNITY (Federal Gov)

Aug 1 2010 - Jul 31 2012

GENERATION AND REGULATION OF ISLET-REACTIVE MEMORY CD4 T CEL LS IN T CELLS IN T 1D (Private)

Jul 1 2010 - Feb 28 2012

COMPARTMENTALIZATION OF ANT-VIRAL CD4 T CELL MEMORY (Federal Gov)

Aug 1 2010 - Jul 31 2011

Selected Publications

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.

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. (2014) Lung resident niches for the generation and maintenance of influenza-specific memory T cells. Mucosal Immunology. 7:501-10.

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., Gordon, C.L. and Farber, D.L. (2014) Tissue resident T cells, in situ immunity and transplantation. Immunol. Reviews. 258:150-166. 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.

Turner, D.L. and Farber, D.L. (2014) Mucosal resident memory CD4 T cells in protection and immunopathology. Front. Immunol. 5:331 Free article

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. (2015) Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit diet-induced obesity. Nature, 519:242-6. PMCID:PMC4447235

Thome, J.J.C. and Farber, D.L. (2015) Emerging concepts in tissue-resident T cells: lessons from humans. Trends. Immunol. 36:428-35. PMCID:PMC4491028

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. Derm. 135: 2688-96. PMCID:PMC4640961

Thome, J.J.C., Bickham, K.L., Kubota, M. Ohmura, Y., Matsuoka, N., Gordon, C., Granot, T., Griesemer, A., Lerner, H., Kato, T., and Farber, D.L. (2016) Early-life compartmentalization of T-cell differentiation and regulatory function in mucosal and lymphoid tissues.  Nature Medicine. 22:72-77. PMCID:PMC4703455

Trischler, J., Shiomi, T., Turner, D.L., Sklepkiewicz, P.L., Goldklang, M.P., Farber, D.L. and D’Armiento, J.M. (2016) Immune Modulation of the T cell Response in Asthma through Wnt10b. Amer. J. Resp. Cell and Mol. Biol. 54:584-93. 

Zuber, J., Rosen, S., Shonts, B., Sprangers, B., Savage, T., Richman, S., Yang, S., Lau, S.P., DeWolf, S., Farber, D.L., Vlad, G., Zorn, E., Wong, W., Emond, J., Levin, B., Martinez, M., Kato, T., Sykes, M. (2015) Macrochimerism in intestinal transplantation: association with lower rejection rates and multivisceral transplants, without GVHD.  Am. J. Transplant. 15:2691-703. 

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.

Farber,D.L., Netea,M., Radbruch,A., Rajewsky,K. and Zinkernagel, R. (2016) Immunological memory: lessons from the past and a look to the future.  Nat. Rev. Immunol. 16: 124-8.

Connors, T.J., Baird, J. and Farber, D.L. (2016) Viral Bronchiolitis in children (correspondance)      N. Engl. J. Med. 374:1791-2.

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(10):e85832. doi:10.1172/jci.insight.85832.  PMCID: PMC4959801

Murray, A.J., Kwon, K.J., Farber, D.L. and Siliciano, R.F. (2016) The latent reservoir for HIV-1: how immunologic memory and clonal expansion contribute to HIV persistence. J. Immunol. 197:407-417. PMCId:PMC4936486 

Zuber J., Shonts, B., Lau, S.-P., Obradovic, A., Fu, J., Yang, S., Lambert, M., Coley, S., Weiner, J., Thome, J.J.C., DeWolf, S., Farber, D.L., Shen, Y., Caillat-Zucman, S., Bhagat, G., Griesemer,A., Martinez,M., Kato, T. and Sykes,M. (2016) Bidirectional intragraft alloreactivity drives the repopulation of human intestinal allografts and correlates with clinical outcome. Sci. Immunol. 1:eaah3732. PMCID:PMC5323244  

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. PMCID: PMC5367636

Nish, S, Zens, K. D. Kratchmarov, R., Lin,W.-H., Adams,W., Chen,Y.-H., Yen,B., Rothman, N., Bhandoola,A., Xue,H.-H., Farber, D.L. and Reiner, S. (2017) CD4+ T Cell Effector Commitment Coupled to Self-renewal by Asymmetric Cell Divisions. J. Exp. Med.  214:39-47. PMCID:PMC5206501

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. PMCID: PMC5339671

Weiner, J., Farber, D.L., Kato, T. and Sykes, M. (2017) Long-term persistence of innate lymphoid cells in the gut after intestinal transplantation. Transplantation, [Epub ahead of print] PMID:27941430

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. PMCID:PMC5415308

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. Nat. Biotech. In Press. 

Yocum, G., Turner, D.L., Danielsson, J. Barajas, M., Zhang, Y., Xu, D. Harrison, N., Homanics, G., Farber, D.L., and Emala, C. (2017) GABAA Receptor α4 Subunit Knockout Enhances Lung Inflammation and Airway Reactivity in a Murine Asthma Model. Am. J. Physiol.-Lung Cell. Mol. Physiol.doi: 10.1152/ajplung.00107.2017 (epub ahead of print).

Snyder, M.E. and Farber, D.L. (2017) Thymic-peripheral crosstalk in lymphoodepletion therapy. Am. J. Trans. 17:1970-1971.

Klose, C.S.N., Mahlakõiv, T., Moeller, J. B., Rankin, L.C., Flamar, A.-L., Kabata, H., Monticelli, L.A., Moriyama, S., Garbès Putzel, G., Rakhilin, N., Shen, X., Kostenis, E., König, G.M., Senda, T., Carpenter, D., Farber, D.L. and Artis, D. (2017) The neuropeptide neuromedin 2 stimulates innate lymphoid cells and promotes type 2 inflammation. Nature: In Press.

Turner, D.L., Goldklang, M., Trischler, J., Cvetkovski, F., D’Armiento, J.M., and Farber, D.L. (submitted) Biased Generation and in situ activation of lung tissue-resident memory CD4 T cells in the pathogenesis of allergic asthma. J. Immunol. In revision.

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., 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. In Press.

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. In Press.

Carpenter, D.J., Matsuoka, N., Granot, T., Kumar, B.V., Senda, T., Thome, J.J.C., Gordon, C.L., Miron, M., Weiner, J., Lerner, H., Friedman, A., Griesemer, A.D., Farber, D.L. (2017) Human immunology studies using organ donors: impact of clinical variations on immune parameters in tissues and circulation. Am. J. Trans. doi: 10.1111/ajt.14434. [Epub ahead of print].

Zens, K.D., Connors, T., and Farber, D.L. (2017) Tissue compartmentalization of T cell responses during early life. Semin. Immunopath. In Press.

Kumar, B.V., Connors, T. and Farber, D.L. (submitted) Human T cells in health and homeostasis. Immunity.