About

Alison E. Ringel is an Assistant Professor of Biology and a Core Member of the Ragon Institute at MIT. Her research focuses on understanding the molecular adaptations that enable immune cells, particularly CD8+ T cells, to function and survive within unfavorable environments. She investigates the crosstalk between these immune cells and their environment at a molecular level by dissecting the biological and metabolic programs engaged under conditions of stress. Her work aims to model and perturb the local microenvironment to reveal adaptive molecular changes and intrinsic vulnerabilities in T cells that arise within the tumor niche. The ultimate goal of her research is to understand how disease states remodel the mechanisms that regulate immune cell function and contribute to pathogenesis.

Research topics

• Biochemistry
• Cancer research
• Biology
• Immunology
• Endocrinology

Selected publications

• Abstract 2099: Iron supplementation rescues anemia of chronic disease in pancreatic ductal adenocarcinoma.

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Pancreatic cancer is a devastating malignancy that is rising in incidence and has nearly universal poor outcomes. We find rates of iron deficiency are high in pancreatic cancer patients and track with the high prevalence of anemia in these patients. From an evolutionary perspective, anemia of chronic disease is a condition seen where our bodies respond to an inflammatory insult, such as an infection, by sequestering iron from circulation to store the iron in peripheral tissues, such as muscle, to make this iron unavailable for pathogens. Our recent preliminary data suggest pancreatic cancer may act as the inflammatory stimulus to cause iron dysregulation and anemia. Analysis of a large cohort of pancreatic cancer patients shows both iron and hemoglobin decrease early in pancreatic cancer patients, suggesting of dysregulated iron metabolism. When pancreatic cancer is modeled in mice, decreases in hemoglobin and iron are also observed, as are increases in circulating hepcidin. Interestingly, supplementing mice with pancreatic cancer with iron improves anemia. Mechanistically, we want to understand why mice with PDAC develop anemia and analyzed Ter119-expressing erythrocyte differentiation and maturation in the bone marrow. We found that there is no defect in erythroid maturation in PDAC mice therefore its unlikely that defective erythropoiesis is the cause for anemia in PDAC. We also profiled Ter119-expression on the surface of F4/80-positive macrophages as a measure of hemophagocytosis and found that there is decreased Ter119-positive macrophages in PDAC so hemophagocytosis in the bone marrow is not the caused of anemia in PDAC. We find that iron-sequestering proteins such as hepcidin are increased throughout PDAC progression and iron sequestration in tumors and we find iron sequestration by many different cell types and tissues during PDAC. Hepcidin is known to cause iron sequestration in macrophages, which are the largest source of iron recycling and supply for heme and hemoglobin synthesis in the body. Furthermore, we observed decreased macrophage numbers in the bone marrows of PDAC mice. Hence, we proposed that PDAC leads to reduced iron-recycling by macrophages and this causes anemia of chronic disease. Therefore, iron supplementation is sufficient to rescue anemia in PDAC. Citation Format: Yichi (Tony) Zhang, Cindy Pyo, Anna Barbeau, Davey Feng, Amit Roopan, Matthew Vander Heiden, Kendra Libby, Alison Epstein Ringel. Iron supplementation rescues anemia of chronic disease in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2099.

  PublisherDOI

• FIP200 regulates plasma B cell differentiation via mitochondrial and heme homeostasis

  The Journal of Experimental Medicine · 2025-11-14

  articleOpen access

  Little is known about the role of autophagy in the human humoral immune system. Here, we found that in B cells, genetic ablation of FIP200, a mammalian metabolic sensor that regulates autophagy in response to a range of stimuli, led to diminished humoral immune responses in mice. FIP200-deficient B cells displayed decreased differentiation into plasma cells, as well as mitochondrial dysfunction, alterations in heme biosynthesis, and significant cell death. Notably, the addition of heme was sufficient to rescue plasma cell differentiation of FIP200-deficient B cells. Thus, FIP200 determines B cell fates by controlling mitophagy and metabolic reprogramming.

  PublisherDOI

• Systems analysis reveals alternate metabolic states adopted by <i>Mycobacterium tuberculosis</i> across species

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-15 · 1 citations

  preprint

  (Mtb) persists within macrophages, yet how different host species shape bacterial state remains poorly understood. Here, we directly compared the intracellular transcriptome of Mtb during infection of human and mouse macrophages, revealing distinct host-imposed microenvironments that drive the pathogen into separable metabolic states. Lipid metabolism and regulatory circuits were prominently remodeled, with mouse macrophages inducing iron- and oxidative-stress responses while human macrophages promoted fatty acid import programs. Using fluorescent fatty acid tracing, we uncovered a striking species-specific phenotype: Mtb forms intracellular lipid inclusions (ILIs) in murine macrophages but not in human macrophages. This phenotype was independent of culture media, macrophage ontogeny, or host antimicrobial factors such as nitric oxide and itaconate. Access of Mtb to host-derived lipids required the ESX-1 secretion system and was inversely correlated with host triacylglycerol (TAG) synthesis. Inhibition of TAG formation in human macrophages partially restored Mtb ILI formation, revealing a metabolic gate that governs lipid flow between host lipid droplets and intracellular Mtb. Together, these findings establish a cross-species framework for decoding host-driven bacterial metabolic states and identify a key barrier limiting Mtb's access to host lipid stores in human macrophages.

  PublisherDOI

• Immunometabolic defects of CD8+ T cells disrupt gut barrier integrity in people with HIV

  Cell · 2025-09-11 · 7 citations

  articleOpen access
  PublisherOA PDFDOI

• PD-1 regulates tumor-infiltrating CD8+ T cells in both a cell-intrinsic and a cell-extrinsic fashion

  The Journal of Experimental Medicine · 2025-07-24 · 5 citations

  articleOpen access

  Although PD-1 inhibitors are FDA-approved for over 25 different cancers, the mechanisms contributing to response remain incompletely understood. To investigate how PD-1-deleted CD8+ T cells influence PD-1-expressing CD8+ T cells in the same tumor microenvironment, we developed an inducible PD-1 knockout (KO) model in which PD-1 is deleted on ∼50% of cells. PD-1 deletion beginning at day 7 after implantation of MC38 tumor cells led to robust tumor control. Remarkably, PD-1-expressing CD8+ T cells in the tumor had increased functionality similar to PD-1 KO CD8+ T cells. Using single-cell RNA-seq and TCR-seq, we found that the major transcriptional changes following PD-1 deletion were shared by PD-1 KO and PD-1-expressing CD8+ T cells, although PD-1 KO clones preferentially expanded. These data suggest PD-1 inhibitors not only exert cell-intrinsic effects but also may promote increased T cell function through non-cell-autonomous mechanisms, which has important implications for design of PD-1-based cancer immunotherapies.

  PublisherOA PDFDOI

• Ageing, immune fitness and cancer

  Nature reviews. Cancer · 2025-08-14 · 20 citations

  review
  PublisherDOI

• Emerging insights into the impact of systemic metabolic changes on tumor-immune interactions

  Cell Reports · 2025-01-23 · 18 citations

  reviewOpen accessSenior author

  Tumors are inherently embedded in systemic physiology, which contributes metabolites, signaling molecules, and immune cells to the tumor microenvironment. As a result, any systemic change to host metabolism can impact tumor progression and response to therapy. In this review, we explore how factors that affect metabolic health, such as diet, obesity, and exercise, influence the interplay between cancer and immune cells that reside within tumors. We also examine how metabolic diseases influence cancer progression, metastasis, and treatment. Finally, we consider how metabolic interventions can be deployed to improve immunotherapy. The overall goal is to highlight how metabolic heterogeneity in the human population shapes the immune response to cancer.

  PublisherDOI

• Integrated analysis of transcriptional and metabolic responses to mitochondrial stress

  Cell Reports Methods · 2025-04-01 · 4 citations

  articleOpen access

  Mitochondrial stress arises from a variety of sources, including mutations to mitochondrial DNA, the generation of reactive oxygen species, and an insufficient supply of oxygen or fuel. Mitochondrial stress induces a range of dedicated responses that repair damage and restore mitochondrial health. However, a systematic characterization of transcriptional and metabolic signatures induced by distinct types of mitochondrial stress is lacking. Here, we defined how primary human fibroblasts respond to a panel of mitochondrial inhibitors to trigger adaptive stress responses. Using metabolomic and transcriptomic analyses, we established integrated signatures of mitochondrial stress. We developed a tool, stress quantification using integrated datasets (SQUID), to deconvolute mitochondrial stress signatures from existing datasets. Using SQUID, we profiled mitochondrial stress in The Cancer Genome Atlas (TCGA) PanCancer Atlas, identifying a signature of pyruvate import deficiency in IDH1-mutant glioma. Thus, this study defines a tool to identify specific mitochondrial stress signatures, which may be applied to a range of systems.

  PublisherDOI

• Figure S5 from Age-Associated Contraction of Tumor-Specific T Cells Impairs Antitumor Immunity

  2024-11-04

  preprintOpen accessSenior author

  &lt;p&gt;Supplemental Figure 5&lt;/p&gt;

  PublisherOA PDFDOI

• Figure S6 from Age-Associated Contraction of Tumor-Specific T Cells Impairs Antitumor Immunity

  2024-11-04

  preprintOpen accessSenior author

  &lt;p&gt;Supplemental Figure 6&lt;/p&gt;

  PublisherOA PDFDOI

Frequent coauthors

• Marcia C. Haigis

  Boston VA Research Institute

  80 shared

• Arlene H. Sharpe

  Massachusetts General Hospital

  58 shared

• Cynthia Wolberger

  Johns Hopkins University

  46 shared

• Jefte M. Drijvers

  44 shared

• Cong-Hui Yao

  Harvard University

  35 shared

• Shakchhi Joshi

  Massachusetts General Hospital

  35 shared

• Peter Georgiev

  33 shared

• Thao H. Nguyen

  Harvard University

  31 shared

Education

• Graduate Student, Biophysics and Biophysical Chemistry

  Johns Hopkins School of Medicine

  2015

• Undergraduate student

  Wesleyan University

  2009

Awards & honors

• Forbeck Scholar (2021)