About

Professor Ananda Goldrath's research focuses on the mechanisms underlying immunological memory, particularly how memory T cells are generated and maintained. His lab investigates the signaling pathways and molecular events that regulate the survival and differentiation of T cells as they respond to infections and develop into long-lived memory cells. This work is crucial for understanding how the immune system remembers pathogens and provides protection upon subsequent exposures, which is the fundamental principle behind vaccination. The Goldrath Lab aims to identify the transcriptional and signaling events that control memory T cell numbers and their functional capacity. Vaccines have been among the most effective medical interventions, exemplified by the eradication of smallpox and the near elimination of polio. However, many diseases remain challenging for conventional vaccine strategies, and the immune system's potential to combat tumors is an emerging area of interest. Ultimately, Professor Goldrath's research seeks to develop new methods to harness the immune system to protect against infections and eradicate malignancies.

Research topics

• Biology
• Genetics
• Immunology
• Medicine
• Cell biology
• Literature
• Pathology
• Art
• Environmental ethics
• Neuroscience
• Philosophy
• Biochemistry

Selected publications

• Multi-omic profiling of human antibody-secreting cells reveals diverse subsets sustain durable humoral immunity - preprint data and code

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-10

  datasetOpen access

  Data and code associated with the manuscript, "Multi-omic profiling of human antibody-secreting cells reveals diverse subsets sustain durable humoral immunity." Each dataset is enclosed in a separate zip file.

  PublisherDOI

• Distinct tissue niches contribute to prostate tissue-resident memory CD8+ T cell differentiation and heterogeneity

  Immunity · 2026-04-01

  articleOpen accessSenior author

  T cells were most persistent, cytotoxic, and enriched for the Trm molecular program. In sum, we provide a spatial framework for prostate Trm cell differentiation, charting the discrete tissue regions that influence T cell fate through dynamic regulation of localized signals.

  PublisherDOI

• Neuro-epithelial circuits promote sensory convergence and intestinal immunity

  Nature · 2026-01-07 · 7 citations

  article
  PublisherDOI

• Proteostasis sustains T cell differentiation potential and tumor-infiltrating lymphocyte function

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-10 · 1 citations

  articleOpen accessSenior authorCorresponding

  Summary Tumor-infiltrating lymphocytes (TIL) often fail to restrain tumor growth due to progressive differentiation to an ‘exhausted’ state. In healthy tissues, tissue-resident memory T cells (T RM ) maintain protection for years, and patient tumors that contain TIL with T RM features are associated with better prognosis. Proteomic and transcriptomic profiling of T cell populations identified proteostasis as a significant factor distinguishing T RM and progenitor-exhausted TIL from terminally-exhausted TIL, including loss of E3 ubiquitin ligases NEURL3, RNF149, and WSB1, with accumulation of unfolded proteins in spite of functional proteasome activity. Enforced expression of these ligases by TIL preserved stem-like TCF1 + populations and improved anti-tumor function, whereas their knockout impaired TIL and altered T cell differentiation in acute infection. Sustained ligase expression rescued accumulation of unfolded proteins in TIL and improved immunotherapy outcome in preclinical models, highlighting the critical role of proteostasis in TIL function and identifying new avenues for advancing cancer immunotherapy.

  PublisherDOI

• Author Correction: Multi-omic profiling reveals age-related immune dynamics in healthy adults

  Nature · 2026-04-10

  articleOpen access
  PublisherOA PDFDOI

• Multi-omic profiling of human antibody-secreting cells reveals diverse subsets sustain durable humoral immunity

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-17

  articleOpen access

  Antibody-secreting cells (ASCs) provide humoral immunity that can mediate lifelong protection against pathogens. Current classifications cannot delineate the heterogenous functionalities, tissue residencies, and lifespans of human ASC subsets, impeding clinical translation. We applied multi-omic sequencing, spatial proteomics, and functional assays to discover and characterize human bone marrow (BM) ASC subsets. We identified two peripheral subsets (ASCp) also present in blood and three BM-resident subsets (ASCr), comprising a maturation continuum associated with increased mitochondrial networking, diminished antibody secretion, differential transcription factor motif accessibility, and preferential co-localization in homotypic niches. CD19+9+ASCr and CD19-ASCr exhibited poor recovery years after BM transplantation, indicating a strong dependence on supportive niches. Childhood vaccine antigens were recognized by long-lived ASCr subsets in adults and by immature HLA-DR+ASCp, implying ASCs can differentiate without recent antigen exposure. Our results provide new insights into ASC identity, maturation, and longevity and a generalizable framework for study and manipulation of human ASCs.

  PublisherDOI

• Myeloma and therapy reshape the bone marrow niche to durably constrain immune reconstitution and vaccine responsiveness

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-09 · 1 citations

  articleOpen access

  Summary Infections are the most common cause of non-relapse mortality in multiple myeloma (MM), but the basis of persistent immune dysfunction is obscured by patient heterogeneity and complex treatment regimens, including autologous stem cell transplant (ASCT). We performed longitudinal multi-omic profiling of matched bone marrow and peripheral blood from MM patients across diagnosis, induction, ASCT, and recovery. We found the tumor imposes a compartment-specific immune program where the marrow exhibits metabolic and inflammatory changes that bias hematopoiesis and alter cytotoxic effector programs not mirrored in blood. Adaptive immune reconstitution is impaired up to two years post-ASCT. Half of patients fail to mount IgG responses to high-dose non-adjuvanted influenza vaccine, a defect overcome by the lipid nanoparticle (LNP) adjuvanted COVID mRNA vaccine, which elicited responses in all patients, supporting adjuvanted influenza vaccine strategies in MM. Together these findings define how myeloma and its treatment durably reshape immunity from the marrow outward. Highlights Multiple Myeloma marrow and blood show opposing metabolic and inflammatory states Induction therapy selects durable myeloma plasma-cell transcriptional states B cell and follicular helper T deficits blunt antigen responses after transplant COVID-19 vaccination builds immune memory with variable responses to flu vaccination eTOC Multiple myeloma and its treatment leave a lasting imprint on the bone marrow niche. By profiling bone marrow and blood longitudinally at diagnosis, through induction, autologous transplant, and recovery, we show that marrow-local metabolic and inflammatory constraints persist and help explain why influenza vaccination often fails while mRNA vaccination succeeds.

  PublisherDOI

• immgenT: A Comprehensive Reference of Convergent T-cell States in the Mouse

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-02

  articleOpen access

  Abstract The immgenT collaborative project generated a comprehensive molecular atlas of T cells spanning virtually all mouse organs and disease states, profiling ∼800,000 cells from 750 samples with RNA, 128-plex surface protein, and αβTCR sequence. Applying a deep generative model to joint RNA and protein data defined a finite landscape of T-cell states organized into eight lineages and 110 robust clusters, integrating identical cells from different contexts, and resolving prior nomenclatures. Analysis of effector molecules, transcription factors and modules showed that both immunological functions and regulatory programs are shared across cell states. This framework provides a stable, reusable reference, demonstrated by computationally integrating 16 external datasets from diverse biological contexts. A set of public web tools supports browsing of these data, allows mapping of any dataset onto the immgenT framework. These results propose a molecular classification of T cells organized around a set of shared states reused across immunological contexts.

  PublisherDOI

• The CD8 immgenT framework as a universal reference of mouse CD8αβ T cell differentiation states

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-04

  articleOpen accessCorresponding

  Mouse CD8 T cell differentiation has been studied extensively in models of infections and cancer, yet no unified framework spans the full spectrum of immunological contexts. We present the CD8 immgenT framework, integrating >200,000 single-cell transcriptomes and 128-plex surface proteomes from 734 samples spanning multiple perturbations, tissues, and timepoints. Unbiased analysis identifies 21 states encompassing naive, effector, circulating memory, tissue-resident memory, progenitor-exhausted, and terminally-exhausted compartments, among others. These states re-emerge with striking molecular convergence across acute/chronic infections, cancer, autoimmunity, aging, and homeostasis, showing that near-identical transcriptional programs support protective or dysfunctional outcomes depending on developmental history and microenvironment. Classic archetypes map to discrete clusters but exhibit unappreciated heterogeneity and overlap, cautioning against rigid nomenclature. We provide validated combinatorial markers, flow cytometry gating strategies, and immgenT reference-based integration for reproducible annotation of new datasets. This universal coordinate system harmonizes fragmented CD8 T cell literature and clarifies relationships across diverse immune challenges.

  PublisherDOI

• Multi-omic profiling of human antibody-secreting cells reveals diverse subsets sustain durable humoral immunity - preprint data and code

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-10

  datasetOpen access

  Data and code associated with the manuscript, "Multi-omic profiling of human antibody-secreting cells reveals diverse subsets sustain durable humoral immunity." Each dataset is enclosed in a separate zip file.

  PublisherDOI

Recent grants

• Regulation of T cell immunity to viral infection

  NIH · $5.4M · 2007–2024

• Project 3 - Zuniga

  NIH · $19.6M · 2018–2024

• T cell maintenance: molecular mediators of T cell differentiation and survival

  NIH · $6.1M · 2006–2022

• NIH Grant U19AI109976

  NIH · $21.0M · 2020

• NIH Grant R01AI096852

  NIH · $1.5M · 2017

Frequent coauthors

• Mark P. Rubinstein

  60 shared

• Christophe Benoist

  Harvard University

  55 shared

• Diane Mathis

  Harvard University

  49 shared

• Andrew L. Doedens

  45 shared

• Kutlu G. Elpek

  Sana Biotechnology (United States)

  29 shared

• J. Justin Milner

  University of North Carolina at Chapel Hill

  28 shared

• John T. Chang

  VA San Diego Healthcare System

  28 shared

• Shannon J. Turley

  28 shared