About

Professor Isaac Chiu leads the Chiu Lab at Harvard Medical School within the Department of Immunology. His research focuses on the neuroimmune mechanisms that underlie pain, host defense, and neurodegeneration. The lab investigates how bacterial pathogens interact with the sensory nervous system to produce pain and itch, how peripheral neurons communicate with immune cells in barrier tissues such as the gut, meninges, skin, and lungs to regulate immunity, and the role of Gasdermins and innate immunity in central nervous system neurodegeneration. The Chiu Lab is part of a vibrant scientific community at Harvard Medical School and actively participates in graduate programs in Biological and Biomedical Sciences, Neuroscience, and Immunology, as well as being members of the Harvard Digestive Disease Center and Harvard Stem Cell Institute. Professor Chiu's work has led to significant contributions in understanding the interplay between the nervous and immune systems, particularly in the context of infectious diseases, neurodegenerative disorders, and immune regulation.

Research topics

• Biology
• Cell biology
• Neuroscience
• Immunology
• Medicine
• Endocrinology
• Data Mining
• Information Retrieval
• Genetics
• Computer Science
• Internal medicine
• Cancer research
• Computational biology
• Mathematics
• Evolutionary biology
• Pathology
• Virology
• Statistics

Selected publications

• Neuroimmune interactions in itch

  Elsevier eBooks · 2026-01-01

  book-chapterSenior author
  PublisherDOI

• Neuroimmune interferon signals sustain arthritis pain

  Nature Neuroscience · 2026-03-30

  articleSenior author
  PublisherDOI

• Skin inflammation and itch response are independently regulated by distinct nociceptor subsets

  Immunity · 2026-04-15

  articleOpen access

  peptidergic neurons exacerbated inflammation through increased neutrophilic infiltration without impacting itch-evoked behavior. This study reveals the presence of two distinct and adaptive neuronal circuits that independently regulate allergic inflammation and itch in the skin.

  PublisherDOI

• The meninges host a distinct compartment of regulatory T cells that preserves brain homeostasis

  Science Immunology · 2025-01-28 · 47 citations

  articleOpen access

  Our understanding of the meningeal immune system has recently burgeoned, particularly regarding how innate and adaptive effector cells are mobilized to meet brain challenges. However, information on how meningeal immunocytes guard brain homeostasis in healthy individuals remains limited. This study highlights the heterogeneous, polyfunctional regulatory T cell (T reg ) compartment in the meninges. A T reg subtype specialized in controlling interferon-γ (IFN-γ) responses and another dedicated to regulating follicular B cell responses were substantial components of this compartment. Accordingly, punctual T reg ablation rapidly unleashed IFN-γ production by meningeal lymphocytes, unlocked access to the brain parenchyma, and altered meningeal B cell profiles. Distally, the hippocampus assumed a reactive state, with morphological and transcriptional changes in multiple glial cell types. Within the dentate gyrus, neural stem cells underwent more death and were blocked from further differentiation, which coincided with impairments in short-term spatial-reference memory. Thus, meningeal T regs are a multifaceted safeguard of brain homeostasis at steady state.

  PublisherOA PDFDOI

• Neuronal VPS13D loss drives microglial activation

  Nature Structural & Molecular Biology · 2025-07-11

  articleSenior author
  PublisherDOI

• Neurotransmitter and neuropeptide regulation of gut immunity

  Current Opinion in Neurobiology · 2025-05-01 · 8 citations

  reviewSenior author
  PublisherDOI

• Vagal TRPV1 ⁺ sensory neurons protect against influenza virus infection by regulating lung myeloid cell dynamics

  Science Immunology · 2025-08-01 · 8 citations

  articleSenior authorCorresponding

  Influenza viruses are a major global cause of morbidity and mortality. Although vagal TRPV1 + nociceptive sensory neurons are known to mediate defenses against harmful agents, including pathogens, their function in lung antiviral defenses remains unclear. Our study demonstrates that both systemic and vagal-specific ablation of TRPV1 + nociceptors reduce survival in mice infected with influenza A virus (IAV). Despite no difference in viral load, mice lacking TRPV1 + neurons exhibited increased viral spread, exacerbated lung pathology, and elevated levels of proinflammatory cytokines. Loss of TRPV1 + neurons altered the lung immune landscape, including an expansion of neutrophils and monocyte-derived macrophages. Transcriptional analysis revealed impaired interferon signaling in myeloid cells and an imbalance in distinct neutrophil subpopulations in the absence of nociceptors. Furthermore, antibody-mediated depletion of myeloid cells during IAV infection substantially improved survival after nociceptor ablation, underscoring the role of TRPV1 + neurons in preventing pathogenic myeloid cell states that contribute to IAV-induced mortality.

  PublisherDOI

• Molecular basis for shifted receptor recognition by an encephalitic arbovirus

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-02

  preprintOpen access

  After decades of inactivity throughout the Americas, western equine encephalitis virus (WEEV) recently re-emerged in South America, causing a large-scale outbreak in humans and horses. WEEV binds protocadherin 10 (PCDH10) as a receptor; however, nonpathogenic strains no longer bind human or equine PCDH10 but retain the ability to bind avian receptors. Highly virulent WEEV strains can also bind the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as alternative receptors. Here, by determining cryo-electron microscopy structures of WEEV strains isolated from 1941-2005 bound to mammalian receptors, we identify polymorphisms in the WEEV spike protein that explain shifts in receptor dependencies and that can allow nonpathogenic strains to infect primary cortical neurons. We predict the receptor dependencies of additional strains and of a related North American alphavirus. Our findings have implications for outbreak preparedness and enhance understanding of arbovirus neurovirulence through virus receptor binding patterns.

  PublisherDOI

• Sensory neurons on guard: roles in pathogen defense and host immunity

  Current Opinion in Immunology · 2025-02-26 · 5 citations

  reviewOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Molecular basis for shifted receptor recognition by an encephalitic arbovirus

  Cell · 2025-04-06 · 11 citations

  articleOpen access

  Western equine encephalitis virus (WEEV) is an arbovirus that historically caused large outbreaks of encephalitis throughout the Americas. WEEV binds protocadherin 10 (PCDH10) as a receptor, and highly virulent ancestral WEEV strains also bind low-density lipoprotein receptor (LDLR)-related proteins. As WEEV declined as a human pathogen in North America over the past century, isolates have lost the ability to bind mammalian receptors while still recognizing avian receptors. To explain shifts in receptor dependencies and assess the risk of WEEV re-emergence, we determined cryoelectron microscopy structures of WEEV bound to human PCDH10, avian PCDH10, and human very-low-density lipoprotein receptor (VLDLR). We show that one to three E2 glycoprotein substitutions are sufficient for a nonpathogenic strain to regain the ability to bind mammalian receptors. A soluble VLDLR fragment protects mice from lethal challenge by a virulent ancestral WEEV strain. Because WEEV recently re-emerged in South America after decades of inactivity, our findings have important implications for outbreak preparedness.

  PublisherDOI

Recent grants

• The role of nociceptor neurons in bacterial host defense and inflammation

  NIH · $270k · 2015–2017

• NIH Grant F32NS076297

  NIH · $54k · 2013

• Sensory Neuron-Bacteria Interactions in Modulating Pain and the Host Microbiota

  NIH · $2.7M · 2016–2021

• Pain and Neuro-immune Signaling in S. pyogenes pathogenesis

  NIH · $639k · 2017–2022

• NIH Grant F32NS07629701

  NIH · $51k · 2013

Frequent coauthors

• Michael C. Carroll

  Harvard University

  48 shared

• Liwen Deng

  Harvard University

  42 shared

• N. Verna

  L'organizzazione Ospedale di Civitanova M

  39 shared

• Elisabeth M. Alicot

  Boston Children's Hospital

  39 shared

• Francis D. Moore

  University of Florida

  38 shared

• William G. Austen

  Harvard University

  36 shared

• Min Xu

  36 shared

• Herbert B. Hechtman

  Chestnut Hill College

  30 shared

Labs

• Chiu LabPI

Education

• Ph.D., Neuroscience

  Harvard University

  2015

• B.S., Neuroscience

  University of California, Berkeley

  2010