About

Staci D. Bilbo is the Haley Family Professor of Psychology and Neuroscience at Duke University School of Medicine. She serves as the Interim Chair of the Department of Neurobiology and holds multiple titles including Professor of Psychology and Neuroscience, Professor of Neurobiology, Professor in Cell Biology, and Professor in Integrative Immunobiology. She is a faculty network member of the Duke Institute for Brain Sciences. Her research focuses on the fields of psychology, neuroscience, neurobiology, cell biology, and immunobiology, contributing to the understanding of brain and immune system interactions.

Research topics

• Biology
• Internal medicine
• Medicine
• Immunology
• Computer Science
• Sociology
• Psychology
• Neuroscience
• Physiology
• Genetics
• Endocrinology
• Evolutionary biology
• Cognitive science
• Philosophy
• Epistemology
• Virology

Selected publications

• Electrical stimulation of the vagus nerve improves amyloid pathology in delirium superimposed on dementia

  Bioelectronic Medicine · 2026-01-16 · 1 citations

  articleOpen access

  Delirium and delirium superimposed on dementia (DSD) are common complications affecting patients suffering from ongoing neurodegenerative pathologies. Peripheral surgical trauma can trigger neuroinflammation and ensuing DSD via mechanisms that remain poorly understood. Given the multifactorial therapeutic effects of neuromodulation, including vagal nerve stimulation, we have tested a minimally invasive approach to combat DSD following orthopedic surgery. We performed orthopedic surgery on 5xFAD and CVN-AD mice and tested the efficacy of minimally invasive percutaneous vagus nerve stimulation (pVNS). We applied immunohistochemical, biochemical, and behavioral assays to evaluate the impact of surgery on postoperative delirium on DSD pathology in Alzheimer’s disease-like mice. To confirm the role of systemic factors in neuroinflammation and amyloid-β dyshomeostasis, we conducted experiments using interleukin-6 (IL-6), a cytokine commonly upregulated in postoperative delirium and in vitro co-culture assays for validation. In AD-like mice surgery induced acute changes in amyloid-β; perioperative treatment with pVNS effectively reduced amyloid-β load, plaque sphericity, and neuronal loss. The rescue of these pathological hallmarks led to improved delirium-like behavior, as demonstrated by the 5-choice serial reaction time task on postoperative days 1 and 2. pVNS improved microglial morphology, particularly near amyloid-β plaques. Acute isolation of microglial cells from 5xFAD mice after surgery indicated that pVNS partially enhanced key Disease-Associated Microglia (DAM) markers. The contribution of pro-inflammatory cytokines to amyloid-β aggregation was validated using an in vitro transwell culture model following Cytomix exposure, which also caused endothelial barrier disruption. Finally, we isolated IL-6 as a well-established biomarker of postoperative delirium and described its role in DSD pathology following systemic administration. These findings establish a role for neuromodulation after pVNS in regulating perioperative immunity and advance a new paradigm for perioperative interventions in patients at risk for DSD.

  PublisherOA PDFDOI

• CGRP reception potentiates anxiety in an influenza A derived immune engram

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-22

  articleOpen accessSenior author

  An immune engram is a recently described phenomenon in which neuronal populations encode functional aspects of an immune challenge. Here we investigate an immune engram arising from respiratory infection with influenza A virus, demonstrating a molecular mechanism with differential influence over behavioral and immunological aspects of the engram. We first define a cellular response to acute non-neurotropic influenza A/Puerto Rico/8/1934 (PR8) infection by mapping cFos+ cells and microglia morphology across brain regions. In the posterior insula, this response has an early peak at 3 days post infection. Using a cre-dependent excitatory chemogenetic system in TRAP2 mice, we capture an engram at this same region and infection timepoint. Activation of this PR8 engram results in anxiety behavior and increased transcriptional expression of cytokines in lung tissue but not spleen tissue. We further explore how pulmonary signals contribute to this PR8 engram. Using tissue-specific, cre-dependent expression of diphtheria toxin fragment in Calca-cre mice, we ablate Calca-expressing cells including pulmonary neuroendocrine cells in respiratory tissue. Loss of Calca-expressing cells prevents changes in synaptic engulfment by microglia in the insula during PR8 infection without altering the cellular response to infection in pulmonary tissue. Signaling of calcitonin gene related peptide (CGRP), a peptide encoded by Calca, can be blocked with the small molecule CGRP receptor antagonist rimegepant. Using rimegepant during acute PR8 infection we again demonstrate that loss of Calca signaling prevents the cellular response to PR8 infection in the insula. Finally, applying rimegepant alongside the chemogenetic system in TRAP2 mice we show that CGRP receptor antagonism during engram formation prevents anxiety behavior but not peripheral gene expression changes resulting from PR8 engram activation.

  PublisherDOI

• Astrocyte-microglia crosstalk through Hevin and Toll-like receptor signaling controls developmental thalamocortical synapse refinement

  Neuron · 2026-02-19 · 1 citations

  articleOpen access

  Synapse formation and elimination are two crucial processes that occur concurrently in the developing brain. Astrocytes and microglia control both processes, yet how these two major glial cell types of the central nervous system (CNS) communicate to balance synapse formation and elimination is unknown. Astrocytes secrete the synaptogenic protein Hevin/SPARCL1, which induces the formation and plasticity of thalamocortical synapses in the mouse visual cortex. Here, we found that, in addition to this synaptogenic function, Hevin directly signals to microglia by interacting with Toll-like receptor 4 (TLR4). This signaling occurs when Hevin is proteolytically cleaved, producing a C-terminal fragment that is no longer synaptogenic. We found that Hevin, through TLR4, induces a distinct microglial state defined by increased TLR2 expression and phago-lysosomal content in vitro and in vivo. Microglial TLR4 signaling is required for the proper elimination of thalamocortical synapses during early postnatal development.

  PublisherDOI

• Excitatory-neuron-derived interleukin-34 supports cortical developmental microglia function

  Immunity · 2025-07-02 · 14 citations

  articleSenior author
  PublisherDOI

• Microglial MyD88-dependent signaling influences extracellular matrix development and interneuron maturation in the hippocampus

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-11

  preprintOpen accessSenior authorCorresponding

  Parvalbumin interneurons (PVIs) are disrupted across diverse neurodevelopmental disorders, highlighting their vulnerability to developmental perturbations. Inflammation can perturb PVI development and function, and inflammatory mechanisms are often propagated within the brain by microglia. Yet the microglial mechanisms linking inflammatory signals to interneuron development are unclear. To test the role of microglial innate immune signaling in PVI development, we used mice lacking toll-like receptor adaptor MyD88 specifically in microglia. MyD88-deficient microglia showed reduced inflammatory responses but increased early-life phagocytosis of inhibitory synaptic material. In adulthood, males without microglial MyD88 exhibited increased hippocampal PVI density, increased extracellular matrix (ECM) deposition, increased inhibitory signaling, and impaired discrimination behaviors. We determined the cytokine interleukin (IL)-33, which normally drives adult microglial remodeling of the ECM, is developmentally regulated in the hippocampus. MyD88-deficient microglia fail to respond to IL-33, leading to reduced remodeling of the ECM component aggrecan. These results reveal microglial immune signaling via MyD88 regulates hippocampal inhibitory circuit development in a sex-specific manner.

  PublisherDOI

• Systems neuroimmunology: current bottlenecks, research priorities and future directions

  Nature Immunology · 2025-02-12 · 5 citations

  articleOpen access
  PublisherOA PDFDOI

• Sex-specific regulation of microglial MyD88 in HMGB1-Induced anxiety phenotype in mice

  Neurobiology of Stress · 2025-03-23 · 4 citations

  articleOpen accessSenior authorCorresponding

  Stress is a significant risk factor for the development and recurrence of anxiety disorders. Stress can profoundly impact the immune system, and lead to microglial functional alterations in the medial prefrontal cortex (mPFC), a brain region involved in the pathogenesis of anxiety. High mobility group box 1 protein (HMGB1) is a potent pro-inflammatory stimulus and danger-associated molecular pattern (DAMP) released from neuronal and non-neuronal cells following stress. HMGB1 provokes pro-inflammatory responses in the brain and, when administered locally, alters behavior in the absence of other stressors. In this study, we administered dsHMGB1 into the mPFC of male and female mice for 5 days to investigate the cellular and molecular mechanisms underlying HMGB1-induced behavioral dysfunction, with a focus on cell-type specificity and potential sex differences. Here, we demonstrate that dsHMGB1 infusion into the mPFC elicited behavior changes in both sexes but only altered microglial morphology robustly in female mice. Moreover, preventing microglial changes with cell-specific ablation of the MyD88 pathway prevented anxiety-like behaviors only in females. These results support the hypothesis that microglial MyD88 signaling is a critical mediator of HMGB1-induced stress responses, particularly in adult female mice. • Infusion of HMGB1 to PFC causes behavioral changes in male and female adult mice. • Females demonstrate a more robust increase in microglial reactivity in response to HMGB1 administration. • Conditional knockout of MyD88 prevents changes in behavior and microglial reactivity in females in response to HMGB1.

  PublisherDOI

• Prenatal exposure to environmental stressors alters gut macrophage development and gastrointestinal function of male offspring

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-24

  preprintOpen accessSenior authorCorresponding

  Abstract Gastrointestinal (GI) dysfunction is a frequently reported comorbidity of neurodevelopmental disorders (NDDs). Early-life inflammatory challenges from the environment (e.g. infection, toxicants) can increase risk for NDDs but the impact of such stressors on the developing GI tract is not well understood. We investigated possible mechanisms by which GI comorbidities occur in response to environmental stressors using our well-characterized model of combined gestational exposure to air pollution (diesel exhaust particles, DEP) and maternal stress (MS), which induces social deficits in male but not female offspring. We show that DEP/MS disrupts normal GI development, leading to altered small intestine morphology in neonatal males, but not females. Recent evidence shows that resident macrophages of the gut prune enteric neurons during a precise postnatal window. We found decreased pruning of gut enteric neurons by the resident macrophages of the muscularis externa in DEP/MS exposed males at postnatal day 14. In line with this, we saw the expression of motor neuron-associated genes spike in males at the same postnatal time point following DEP/MS exposure. Finally, we assessed the motor function of the GI tract of these animals and observed dysmotility in DEP/MS males only. Taken together, these findings establish intestinal macrophages as a mediator of GI development that is sensitive to early-life perturbations from the environment, highlighting a potential mechanism connecting NDDs with comorbid GI dysfunction.

  PublisherOA PDFDOI

• Preventing Microglial Reactivity Protects from Acute and Progressive Neuronal Dysfunction, Motor Impairments and Sedation following Alcohol Abuse

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-15

  preprintOpen access

  Abstract Alcohol abuse is the primary risk factor for alcohol use disorder (AUD), a leading cause of preventable morbidity and mortality, characterized by systemic inflammation, multi-organ damage, and neurological impairments. While direct effects of alcohol on brain function are well-established, the role of microglia in acute and chronic neurological dysfunction in AUD remains unclear. Using longitudinal in vivo imaging in mice during acute and repeated alcohol abuse, we found that microglia exhibit dynamic morphological responses that precede but parallel ethanol-induced sedation. Ethanol also induced microglia-dependent synapse elimination and reduced neuronal activity and density. Genetic disruption of microglial MyD88 reversed these ethanol-associated changes in microglial reactivity, neuronal structure, and function, while protecting against alcohol-induced intoxication and motor impairments. These findings identify microglia as cellular drivers of acute and chronic brain dysfunction following alcohol abuse, and highlight MyD88 as a critical therapeutic target for the detrimental neurological consequences of AUD.

  PublisherOA PDFDOI

• Microglial pro-inflammatory signaling influences male parvalbumin interneuron development in the hippocampus

  Brain Behavior and Immunity · 2024-11-01

  articleSenior author
  PublisherDOI

Recent grants

• Sex Differences in Developing Microglia: Implications for Synaptic Pruning

  NIH · $2.0M · 2016–2018

• NIH Grant R01DA025978

  NIH · $1.0M · 2013

• NIH Grant F32MH076320

  NIH · $95k · 2008

• Environmental Toxins and Microglia-Synapse Interactions in Autism

  NIH · $2.1M · 2016–2021

• Neural-Glial Interactions and Opioid Abuse: Modulation by Early-Life Experience

  NIH · $1.8M · 2013–2019

Frequent coauthors

• J-Y Sung

  Kyung Hee University

  242 shared

• Steven Swanson

  Brigham and Women's Hospital

  242 shared

• Kyung‐Min Kim

  Kyungpook National University

  242 shared

• L Wong

  Kyung Hee University

  242 shared

• Jong Min Lee

  Seoul St. Mary's Hospital

  242 shared

• Aditi Hazra

  Harvard University

  242 shared

• Laura C. Collins

  Hadassah Medical Center

  242 shared

• Virginia A. LiVolsi

  Hospital of the University of Pennsylvania

  242 shared