About

Ai Ing Lim is an incoming Assistant Professor of Molecular Biology at Princeton University. Originally from Malaysia, she received her master’s degree from The University of Hong Kong. She completed her graduate studies at the Pasteur Institute in Paris under the mentorship of Prof. James Di Santo as a European Union Marie Curie Fellow, where she identified innate lymphocyte precursors from the blood and tissues of healthy individuals. During her postdoctoral training at the National Institutes of Health in the laboratory of Dr. Yasmine Belkaid, supported by a Human Frontier Science Program fellowship, she discovered that maternal infection can provide pre-birth immune education to the offspring in a tissue-specific manner. Her work demonstrated that the immune system is highly plastic and can adapt to environmental challenges even before birth, with her research encompassing both human and murine immunology. Her contributions have been recognized through several awards, including being named an International Rising Talent by L’Oreal-UNESCO, receiving the European Federation of Immunological Societies’ ACTERIA Doctoral Prize, and the Sidney & Joan Pestka Post Graduate Award by the International Cytokine and Interferon Society. Her research focuses on deciphering maternal-offspring immune crosstalk, particularly how maternal infection impacts offspring immunity and predisposition to immune disorders, as well as understanding maternal immune adaptation during pregnancy and lactation, with the ultimate goal of improving health trajectories in children.

Research topics

• Biology
• Immunology
• Cell biology
• Chemistry
• Genetics

Selected publications

• Bioelectric and Mechanotransductive Modulation of Mast Cell Activation Thresholds as a treatment for MCAS

  Zenodo (CERN European Organization for Nuclear Research) · 2026-01-07

  otherOpen accessSenior author

  This paper presents a novel conceptual framework for understanding and treating mast cell hypersensitivity, with a focus on Mast Cell Activation Syndrome (MCAS). Rather than emphasizing downstream mediator release or immune signaling pathways, the work reframes mast cell dysfunction as a disorder of altered activation threshold regulation. The paper proposes that mast cell sensitivity is governed, in part, by intrinsic bioelectric and mechanotransductive mechanisms that shape cellular excitability upstream of calcium-dependent activation. By integrating principles from immunology, biophysics, and systems biology, the paper introduces a unified model in which membrane potential stability, ion channel dynamics, and mechanical signal processing converge to determine whether mast cells activate in response to diverse stimuli. This framework offers a biologically plausible explanation for the heterogeneity and unpredictability of triggers observed in MCAS and highlights previously underexplored regulatory layers that may be therapeutically targeted.

  PublisherDOI

• Bioelectric–Mechanotransductive Coupling Defines Mast Cell Activation Thresholds

  Open MIND · 2026-01-07

  otherSenior author

  This paper presents a novel conceptual framework for understanding and treating mast cell hypersensitivity, with a focus on Mast Cell Activation Syndrome (MCAS). Rather than emphasizing downstream mediator release or immune signaling pathways, the work reframes mast cell dysfunction as a disorder of altered activation threshold regulation. The paper proposes that mast cell sensitivity is governed, in part, by intrinsic bioelectric and mechanotransductive mechanisms that shape cellular excitability upstream of calcium-dependent activation. By integrating principles from immunology, biophysics, and systems biology, the paper introduces a unified model in which membrane potential stability, ion channel dynamics, and mechanical signal processing converge to determine whether mast cells activate in response to diverse stimuli. This framework offers a biologically plausible explanation for the heterogeneity and unpredictability of triggers observed in MCAS and highlights previously underexplored regulatory layers that may be therapeutically targeted.

  DOI

• Bioelectric–Mechanotransductive Coupling Defines Mast Cell Activation Thresholds

  Zenodo (CERN European Organization for Nuclear Research) · 2026-01-07

  otherOpen accessSenior author

  This paper presents a novel conceptual framework for understanding and treating mast cell hypersensitivity, with a focus on Mast Cell Activation Syndrome (MCAS). Rather than emphasizing downstream mediator release or immune signaling pathways, the work reframes mast cell dysfunction as a disorder of altered activation threshold regulation. The paper proposes that mast cell sensitivity is governed, in part, by intrinsic bioelectric and mechanotransductive mechanisms that shape cellular excitability upstream of calcium-dependent activation. By integrating principles from immunology, biophysics, and systems biology, the paper introduces a unified model in which membrane potential stability, ion channel dynamics, and mechanical signal processing converge to determine whether mast cells activate in response to diverse stimuli. This framework offers a biologically plausible explanation for the heterogeneity and unpredictability of triggers observed in MCAS and highlights previously underexplored regulatory layers that may be therapeutically targeted.

  PublisherDOI

• Eosinophils drive intestinal remodelling and innate defence in reproduction

  Nature · 2026-05-13 · 1 citations

  articleOpen accessSenior authorCorresponding

  Mammalian reproduction requires substantial immune adaptations to safeguard reproductive success and to ultimately shape the evolutionary trajectories of a species. Systemic and placental immunity shift towards tolerance during pregnancy1,2; however, how maternal immunity adapts in barrier tissues—which are sites of frequent infection and inflammation—from pregnancy until the postpartum lactation period remains poorly understood. Here we report a previously unrecognized role for eosinophils, a type of granulocyte typically associated with allergies and helminth infections3,4, in remodelling the intestinal barrier during reproduction. Beginning in pregnancy and peaking during lactation, eosinophils accumulate in the small intestine in the absence of infection or inflammation. Using genetic and pharmacological perturbations, organoid cultures and single-cell and spatial transcriptomics, we show that eosinophils promote goblet cell differentiation in a stem-cell-intrinsic manner that leads to increased mucus production. This remodelling culminates during lactation and limits pathogen entry and dissemination to confer broad innate protection against enteric bacterial infections. Moreover, in mice, intestinal remodelling and innate defence persist weeks after lactation cessation. Our findings demonstrate that despite a general trend towards systemic immune modulation during reproduction, the maternal intestine undergoes remodelling to strengthen innate defence, a mechanism that may have evolved to protect mothers and offspring in pathogen-rich environments. More broadly, we establish a framework for studying tissue-specific immune adaptation across the reproductive cycle and highlight that tissues can retain changes following physiological reproduction, with lasting implications for host defence and women’s health. From pregnancy until lactation, eosinophils accumulate in the small intestine where they regulate goblet cell fate and enhance innate defences against enteric pathogens.

  PublisherDOI

• Maternal helminths rewire the microbiota to promote offspring antiviral immunity

  Cell Host & Microbe · 2026-05-01

  articleOpen accessSenior authorCorresponding

  Maternal environmental exposures can alter microbiome composition and lead to changes in offspring immunity. Industrialization has led to significant shifts in the microbiome, but whether these have transgenerational impacts remains unclear. Here, we discovered that maternal helminths, an evolutionarily conserved mammalian partner lost in industrialized societies, confer broad and lasting protection against respiratory viruses in offspring. This heterologous antiviral immunity is mediated by helminth-induced changes in the maternal microbiota. The tryptophan metabolite indole-3-propionic acid (IPA), derived from helminth-altered microbiota, induces lung epithelial IFN-I responses and is sufficient to protect offspring from respiratory syncytial virus (RSV) and influenza A virus infections. Analysis of chronically helminth-infected human populations reveals gut microbiota enriched for tryptophan metabolic capacity. Additionally, IPA treatment is sufficient to enhance antiviral IFN-I signaling in human bronchial epithelial cells. Collectively, this work uncovers the importance of maternal helminth-driven trans-kingdom crosstalk across generations and highlights microbial metabolites as actionable strategies to strengthen antiviral defense. • Maternal helminths promote offspring antiviral immunity via the microbiota • Helminth-altered microbiota produce IPA, which drives antiviral protection • IPA induces lung epithelial type I interferon responses to promote antiviral immunity • Helminth-endemic human microbiota are enriched in the tryptophan metabolism pathway Fernandes et al. show that maternal helminths, long-standing mammalian partners, confer antiviral immunity to offspring via the microbiota-derived metabolite indole-3-propionic acid (IPA). This work reveals helminth-driven trans-kingdom crosstalk across generations and highlights microbiota-derived metabolites as potential strategies to enhance antiviral defense.

  PublisherDOI

• Maternal helminth infection promotes offspring long-term antiviral immunity via microbiota 3855

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Early-life microbiota exposures are crucial for lifelong health. While the effects of antibiotics and processed diets on microbiota are well-studied, the evolutionary role of helminth-altered microbiota is often neglected. Mammals, except humans in high- and middle-income societies over the past century, co-evolved with helminths. These organisms shape microbiota and immunity, but the impact of their absence in modern human health, especially during early development, remains poorly understood. To address this, we developed a maternal helminth infection model using Heligmosomoides polygyrus. Bulk RNA sequencing revealed maternal helminth infection activated type I interferon and antiviral pathways in offspring lung epithelium. This maternal-restricted infection provided lasting protection against respiratory syncytial virus and influenza in offspring. Cross-fostering and antibiotics treatment showed maternal helminth infection enhances lung antiviral immunity during the nurturing period in a microbiota-dependent manner. Transfer cecal microbiota to germ-free mice conferred long-term protection and serum from these microbiota-recipient mice induced interferon in lung epithelium. Using mass spectrometry and metagenomics, our ongoing work aims to identify microbiota components driving antiviral response. These findings offer insights into helminth-microbiota-host interactions and strategies to promote early-life antiviral immunity without reintroducing helminths to humans. Funding Sources Supported by the Branco Weiss Fellowship—Society in Science; Searle Scholars Program; Pew Latin Ammerican Fellowship - The Pew Charitable Trusts Topic Categories Mucosal and Regional Immunology (MUC)

  PublisherOA PDFDOI

• The case for HLA-G as a viable method of cancer eradication

  Zenodo (CERN European Organization for Nuclear Research) · 2025-12-26

  articleOpen accessSenior author

  This paper examines the role of HLA-G as an underrecognized immune tolerance mechanism in cancer and proposes a constraint-removal framework for understanding immunotherapy resistance. Rather than treating immune failure as a problem of insufficient activation, the work reframes tumor immune evasion as the result of dominant upstream tolerogenic signals that suppress cytotoxic immunity independently of classical checkpoints such as PD-1/PD-L1. By integrating biological mechanisms, tumor expression patterns, and emerging translational and clinical signals, the paper outlines a testable model in which targeting HLA-G may restore antitumor immune engagement, particularly in immune-excluded and checkpoint-refractory cancers. The study emphasizes conceptual synthesis and experimental testability, offering a strategic foundation for future translational investigation.

  PublisherDOI

• Deep Learning of Functional Perturbations from Condensate Morphology

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-19

  preprintOpen access

  Abstract Biomolecular condensates compartmentalize the interior of living cells to spatiotemporally organize complex functions, yet linking molecular interactions within condensates to their mesoscale organization remains a major challenge. To bridge this gap, we developed a neural network-based framework - Deep-Phase - that uses microscopy images to quantitatively classify condensate morphology changes resulting from pharmacological alterations in associated biochemical processes. We use Deep-Phase to precisely quantify time- and concentration-dependent structural perturbations to the multiphase nucleolus and show that they are tightly coupled to potencies of drugs inhibiting rRNA transcription and processing. Applying Deep-Phase in a chemical screen, we identify a unique nucleolar morphology and discover a role for a DNA topoisomerase in rRNA processing. Mechanistic studies of this morphology provide insights into how interfaces between nucleolar subcompartments are maintained. We demonstrate Deep-Phase’s adaptability to diverse cell lines, labels, and condensates, offering a powerful platform for uncovering cellular organizing principles and therapeutic targets. Highlights A deep learning framework, Deep-Phase, classifies and quantifies drug-induced changes in morphologies of nucleoli, nucleolar speckles, and viral cytoplasmic condensates, directly from images. Time- and concentration-dependent morphological responses to perturbation predict associated disruptions in RNA transcription and processing. Using Deep-Phase in a high-content small molecule screen reveals a unique nucleolar morphology induced by TOP1 inhibition. TOP1 inhibition leads to reduced levels and processing of large ribosomal subunit precursors and provides a mechanism for maintenance of nucleolar phase boundaries.

  PublisherOA PDFDOI

• Pre-birth stem cell education: A gift from mother’s bugs

  Cell stem cell · 2025-02-01 · 1 citations

  articleSenior author
  PublisherDOI

• A model of early-life interactions between the gut microbiome and adaptive immunity provides insights into the ontogeny of immune tolerance

  PLoS Biology · 2025-08-14 · 4 citations

  articleOpen access

  To achieve immune and microbial homeostasis during adulthood, the developing immune system must learn to identify which microbes to tolerate and which to defend against. How such 'immune education' unfolds remains a major knowledge gap. We address this gap by synthesizing existing literature to develop a mechanistic mathematical model representing the interplay between gut ecology and adaptive immunity in humans during early life. Our results indicate that the inflammatory tone of the microenvironment is the mediator of information flow from pre- to post-weaning periods. We evaluate the power of postnatal fecal samples for predicting immunological trajectories and explore breastfeeding scenarios when maternal immunological conditions affect breastmilk composition. Our work establishes a quantitative basis for 'immune education', yielding insights into questions of applied relevance.

  PublisherDOI

Frequent coauthors

• Jean‐Laurent Casanova

  Université Paris Cité

  52 shared

• Yasmine Belkaid

  National Institute of Allergy and Infectious Diseases

  51 shared

• Verena M. Link

  National Institute of Allergy and Infectious Diseases

  42 shared

• Jacinta Bustamante

  Inserm

  41 shared

• Michel Enamorado

  National Institutes of Health

  39 shared

• Apollo Stacy

  National Institute of Allergy and Infectious Diseases

  34 shared

• Seong‐Ji Han

  National Institutes of Health

  33 shared

• James P. Di Santo

  33 shared

Labs

• Current Lab AssignmentsPI

Education

• PhD in Immunology

  Institut Pasteur, Université Paris Diderot Paris 7, École Doctorale BIO SPC

  2017

• MPhil in Nephrology, Medicine

  University of Hong Kong

  2012

• BSc in Applied Biology with Biotechnology, Department of Applied Biology and Chemical Technology

  Hong Kong Polytechnic University

  2010

Awards & honors

• Lim named 2025 HHMI Freeman Hrabowski Scholar
• 2025 Rosalind Franklin Young Investigator Award Recipients A…
• Lim Lab: Mothers’ secret recipe for fending off infection
• Lim lab: What is lost is not lost
• Lim named 2024 Searle Scholar