About

Donna L. Farber, PhD, is the George H. Humphreys, II Professor of Surgical Sciences (in Surgery) and Professor of Microbiology & Immunology at Columbia University Vagelos College of Physicians and Surgeons. She serves as the Principal Investigator of the Columbia Center for Translational Immunology and is the Chief of the Division of Surgical Sciences. Her research focuses on immunological memory, specifically on memory T cells as essential mediators of protective immunity. Her work has demonstrated that localization and establishment of non-circulating tissue-resident memory T cells (TRM) in tissues are integral to immune protection, with significant findings in lung tissue-resident T cells mediating immunity in influenza infection. She incorporates fundamental studies on mouse models with translational approaches on human samples, collaborating with organ procurement organizations and transplant surgeons to study human lymphocyte compartmentalization and maintenance across the human lifespan. Her ongoing research also investigates infant immunity and how protective responses can be established in vulnerable populations, utilizing both mouse models and human infant samples.

Research topics

• Immunology
• Virology
• Medicine
• Biology
• Pathology
• Genetics
• Environmental health
• Computational biology
• Internal medicine

Selected publications

• <b>A computational pipeline for the spatial analysis of immune cell interactions in lymphoid organs</b>

  Figshare · 2026-04-10

  datasetOpen accessSenior author

  Segmentation files &amp; underlying .qptiffs(HALO output) for:<br>healthy human (D437) : PLN (pleural lung lymph node)<br>Naive mouse: ipLN (intraperitoneal lymph node)

  PublisherDOI

• The human antibacterial factor APOL3 couples lysosomal damage to mitochondrial DNA efflux and type I IFN induction

  Molecular Cell · 2026-02-24

  articleOpen access
  PublisherOA PDFDOI

• Age determines NK cell fate and tissue compartmentalization to CMV infection

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-17

  articleOpen accessSenior authorCorresponding

  ABSTRACT Cytomegalovirus (CMV), a ubiquitous herpesvirus, establishes persistent infection that is controlled by both NK and CD8 T cells. While immunity to CMV is primarily studied in adult mice and humans, most individuals acquire CMV during the early years of life and virus-specific NK and T cell responses during this vulnerable life stage are understudied. Here, we show distinct responses by infant and adult NK cells to CMV infection in both mice and humans resulting from cell-intrinsic features and host T cell responses. Infant mice sustained higher viral loads compared to adults following MCMV infection and exhibited non-redundant requirements for NK cells. Infant MCMV-reactive (Ly49H + ) NK cells preferentially expanded adaptive-like subsets which were maintained in tissues and exhibited a distinct transcriptional profile relative to adult NK cells. This biased differentiation of adaptive-like NK cells was altered over age and controlled in part, by competition with memory T cells. We demonstrate similar dynamics with human NK cells; distinct adaptive-profiles for HCMV-reactive NK cells in early life and childhood that change over age and are inversely associated with anti-viral T cell responses. Together, our results reveal that NK cells develop adaptive-like responses and seed tissues in early life to provide protective memory when T cell immunity is limited. ONE-SENTENCE SUMMARY Memory NK cell generation to cytomegalovirus infection is regulated by age and T cell immunity

  PublisherDOI

• Immune development in early life

  Nature Immunology · 2026-05-22

  article
  PublisherDOI

• <b>A computational pipeline for the spatial analysis of immune cell interactions in lymphoid organs</b>

  Figshare · 2026-04-10

  datasetOpen accessSenior author

  Segmentation files &amp; underlying .qptiffs(HALO output) for:<br>healthy human (D437) : PLN (pleural lung lymph node)<br>Naive mouse: ipLN (intraperitoneal lymph node)

  PublisherDOI

• A lymph node slice culture model to spatially profile early vaccine responses in human tissue 3287

  The Journal of Immunology · 2025-11-01

  articleOpen access

  Abstract Description The activation and spatial interactions of immune and stromal populations in the lymph node (LN) are critical in the formation of adaptive immunity following vaccination. While the induction of immunological memory with vaccination is well established, early responses to vaccines in memory-forming sites such as the LN are less well-characterized in humans. We have developed methods for culturing live human LN slices, which overcome limitations of suspension culture by preserving physiological cell composition, cell-cell interactions, and tissue architecture. To profile acute vaccine responses, we used both LN suspension and slice culture systems stimulated with Merck Measles-Mumps-Rubella (MMR), Pfizer COVID-19 mRNA bivalent booster, or Fluzone influenza vaccines with CITE-seq and 10x Xenium spatial profiling as readouts. CITE-seq revealed an MMR dose-dependent interferon response signature, whereas the Pfizer mRNA vaccine localizes to macrophages, compromising their viability while inducing a glycolytic state in lymphocyte subsets. Xenium profiling recapitulated and provided spatial context for these phenotypes with robust sampling of stromal and innate compartments typically depleted by tissue dissociation. Overall, comparing vaccines with varying antigen/protection profiles in the human LN yielded early, vaccine-specific signatures which may relate to the generation of durable memory responses. Funding Sources Supported by NIH 2U19AI128949-06; DARPA HR001121S0037; NIH 1T32GM145440-01; LiveOnNY and Farber Lab for organ donor tissue samples. Topic Categories Vaccines and Immunotherapy (VAC)

  PublisherOA PDFDOI

• NK cells share a universal signature of memory with B and T cells in mice and humans 3891

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description NK cells, like B and T cells, acquire immune memory; however, our understanding of memory NK cells is primarily limited to specific subsets generated during CMV infection and lacks generalized memory markers. We hypothesized a universal memory signature exists across B, T, and NK cells; thus, we performed whole transcriptional profiling of B, CD4 T, CD8 T, and NK cells over the course of MCMV infection. Indeed, a shared transcriptional signature delineated naïve and memory cells across all lymphocyte populations; including CD55 (DAF, decay accelerating factor), the ectonucleotidase CD39, and the transcription factor Aiolos which were all validated by flow cytometry. As such, naïve cells are CD55hiCD39-Aioloshi and memory are any other combination thereof. The capacity of these markers to delineate memory cells extended to multiple other infectious scenarios and were recapitulated in human memory B and T cells. Single cell transcriptional analysis of human lymphocytes also demonstrated functional distinction between naïve and memory cells. To solidify this memory signature for NK cells, we performed in vitro stimulation and observed upregulation of cytolytic effectors only in memory NK cells. Notably, naïve and memory NK cells exhibit distinct localization throughout the human body. These findings establish a core signature, conserved across cell lineage and species, for identifying memory broadly and provides a foundation for designing strategies to modulate immune memory. Funding Sources NIH AI168634, AI128949, T32AI148099 Topic Categories Viral Immunology (VIR)

  PublisherOA PDFDOI

• Immune mechanisms and predictors of immune protection and vaccine efficacy 4348

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Vaccines have long been pivotal for protection against a host of pathogens, conferring both individual and population-level protection leading to reduced mortality and morbidity across the world. However, vaccine efficacy is highly variable and early predictors of immune response and vaccine-induced memory remain unclear. Here we investigate the early innate-driven mechanisms leading to different grades of induction of adaptive immunity and protection. We vaccinated mice subcutaneously with protective doses of influenza (Sanofi) and SARS-CoV-2 (Pfizer) vaccines and analyzed their immune response in their draining lymph node (inguinal LN) at early time points (6 and 16 hours). When compared to the contralateral LNs, both vaccines led to increased inguinal LN cellularity at rapid times post-vaccination with the influenza vaccine showing earlier peak response at 6 hours compared to SARS-CoV-2 at 16 hours. Moreover, influenza vaccination led to an increase in DCs and B cell numbers, while the SARS-CoV-2 vaccine showed higher numbers of monocytes and NK cells post-vaccination. Preliminary data showed an increase of IFN-induced cytokines (IP-10, MCP-1, MIP-1β, and MIG) at 16 hours post-vaccination in both the serum and draining LN supernatant of SARS-CoV-2-vaccinated mice. Together, these distinct early innate responses induced by vaccination serve as early potential indicators of vaccine efficacy, providing novel correlates of protection for clinical evaluation. Funding Sources DARPA W911NF-23-2-0018 Topic Categories Vaccines and Immunotherapy (VAC)

  PublisherOA PDFDOI

• Tissue signatures of human macrophages during homeostasis and activation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-28

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Human macrophages (MΦs) reside in tissues and develop tissue-specific identities. While studies in mice have identified molecular signatures for site-specific MΦ differentiation, we know less about the transcriptional profiles of human MΦs in distinct sites, including mucosal tissues and lymphoid organs during homeostasis and activation. Here, we use multimodal single-cell sequencing and ex vivo stimulation assays to define tissue signatures for populations of human MΦs isolated from lungs, small intestine, spleen, bone marrow, and lymph nodes obtained from individual organ donors. Our results reveal distinct tissue-adapted gene and protein profiles of metabolic, adhesion, and immune interaction pathways, which are specific to MΦs and not monocytes isolated from the same sites. These signatures exhibit homology to murine MΦs from the same sites. Tissue-adapted MΦs remained responsive to polarizing cytokine stimuli ex vivo , with upregulation of expected transcripts and secreted proteins, while retaining tissue-specific profiles. Together, our findings show how human MΦ identity is coupled to their site of residence for mucosal and lymphoid organs and is intrinsically maintained during activation and polarization.

  PublisherOA PDFDOI

• Anti-viral and anti-commensal antibody repertoires differ across human tissues 3554

  The Journal of Immunology · 2025-11-01

  articleOpen access

  Abstract Description Memory B cells (BRMs) are present in serum, lymphoid organs and non-lymphoid tissues, where they are strategically positioned to provide immediate protection at mucosal and barrier sites. We previously reported that in children aged 1–3 years, BRMs from the lung and lung-associated lymph nodes (LLNs) showed a strong bias toward respiratory pathogens, contrasting with vaccine-specific antibodies (Abs) in serum. To study BRM tissue localization in adults, we used samples from lung, LLN, mesenteric lymph node (MLN), spleen (SPL) bone marrow (BOM) and blood (BLD) from 23 adult donors. Cells were stimulated in-vitro to differentiate into Ab-secreting plasma cells. Using antigen microarrays covering antigens from childhood vaccines, human herpes viruses, common respiratory viruses, and commensal bacteria and fungi, we profiled secreted IgG and IgA and compared these to the serum Ab repertoires. We found significant differences in antigen-specific repertoires across tissues, with both tissue-specific and shared specificities. Responses to childhood vaccines and viruses were more tissue-specific, while responses to commensal bacteria and fungi were more widespread. High anti-CMV titers were associated with reduced anti-commensal responses to some bacterial families. Our findings provide insights into the interplay between tissue-specific immunity and systemic Ab responses, offering valuable information on immune surveillance and defense mechanisms across human tissues. Funding Sources ISF 2683/21 Topic Categories Mucosal and Regional Immunology (MUC)

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01AI042092

  NIH · $1.3M · 2009

• Development of lung T cell responses in infant respiratory immunity

  NIH · $3.9M · 2012–2023

• Admin-Core-001

  NIH · $47.9M · 2017–2027

• NIH Grant R21AI050632

  NIH · $334k · 2003

• Transcriptomics and Repertoire Profiling

  NIH · $51.3M · 2013–2025

Frequent coauthors

• Peter A. Szabo

  Columbia University Irving Medical Center

  37 shared

• Thomas J. Connors

  Columbia University

  34 shared

• Damian Turner

  Williams College

  33 shared

• Masaru Kubota

  Columbia University

  33 shared

• Rei Matsumoto

  Columbia University Irving Medical Center

  29 shared

• Michelle Miron

  28 shared

• Peter A. Sims

  Columbia University Irving Medical Center

  27 shared

• Yufeng Shen

  Columbia University Irving Medical Center

  26 shared

Labs

• Columbia Center for Translational ImmunologyPI

Education

• Ph.D., Molecular Biology

  Columbia University

  1990

• M.D.

  New York University School of Medicine

  1985

• B.A., Biology

  Harvard University

  1981