About

William C. Gause, PhD, is a distinguished researcher and academic leader in the fields of infectious disease and immunology. He received his bachelor's degree from the University of Virginia and completed his PhD at Cornell University in 1986. Following a postdoctoral fellowship at the National Institutes of Health, Dr. Gause joined the faculty of the Uniformed Services University of the Health Sciences in Bethesda, Maryland, in 1989, where he served in the Department of Microbiology and Immunology. In 2004, he transitioned to Rutgers University (formerly the University of Medicine and Dentistry of New Jersey), assuming roles as Senior Associate Dean for Research, Director of the Center for Immunity and Inflammation, and University Professor of Medicine at New Jersey Medical School. His research is internationally recognized and has been continuously funded by the National Institutes of Health since 1991. Dr. Gause has published extensively in prestigious journals, focusing on infectious disease and inflammation, with recent research centered on understanding macrophage function during the type 2 immune response and its role in controlling inflammation and mediating resistance. His work explores the molecular signaling events that trigger immune responses, the coevolution of metazoan parasites with vertebrates, and the development of novel therapies for harmful inflammation and tissue repair.

Research topics

• Immunology
• Biology
• Genetics
• Pathology
• Medicine
• Cancer research
• Cell biology

Selected publications

• Type-2-immune history imprints local training in nerve-airway associated interstitial macrophages (NAMs) for disease tolerance during respiratory viral infection

  Research Square · 2026-02-12

  preprintOpen access
  PublisherOA PDFDOI

• Alveolar macrophages inhibit emphysematous pathology via expression of carbonic anhydrase 4

  Cell Reports · 2026-05-01

  articleOpen access

  Chronic obstructive pulmonary disease (COPD) including emphysema is the fourth leading cause of death worldwide. Therapies to treat COPD remain limited and fail to prevent disease progression. Alveolar macrophages (AMs) reside in the alveoli of the lung and are ideally positioned to encounter inhaled particles and pathogens. Despite exposure to these stimuli, AMs exhibit specialized phenotypes that restrict inflammation to prevent lung damage. Here, we demonstrate that AMs express high levels of the surface-bound enzyme carbonic anhydrase 4 (Car4). Deletion of Car4 on AMs results in increased susceptibility to emphysematous pathology, and therapeutic treatment with Car4 is sufficient to prevent emphysema-like disease. Consistent with murine studies, reduced levels of human Car4 (CA4) distinguish COPD patients with emphysema from those without. Mechanistically, murine and human Car4 directly inhibit neutrophil elastase, which promotes destruction of alveolar walls and drives emphysema. Collectively, these studies reveal the existence of a lung-specific elastase inhibitor that protects the elastin-containing walls of the alveoli and provides important therapeutic insight into a disease that affects 300 million individuals globally.

  PublisherDOI

• Helminth infection favors reprogramming and proliferation of lung neutrophils

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-29

  preprintOpen accessSenior authorCorresponding

  Neutrophils are a granulocytic population of myeloid cells that have critical effector functions during infectious disease but are generally thought to be short-lived and nonproliferative with markedly limited activation states. In these studies, we directly compared lung neutrophil activation following infection with different groups of pathogens including bacteria, fungi, and helminths. Our results demonstrate considerable heterogeneity depending on the type of infectious agent. In contrast to bacterial and fungal infection, after helminth infection neutrophils expressed markers associated with characteristic type 2 responses and unexpectedly upregulated genes associated with cell cycling and protein synthesis. Further studies showed reduced neutrophil cell death following helminth infection and increased proliferation, which was dependent on IL-4R signaling. This distinct subset of proliferating neutrophils expanded following helminth infection and was released from the endothelial niche to colocalize with invading parasites in the airways. These studies demonstrate a novel long-lived cycling phenotype for neutrophils following helminth infection.

  PublisherOA PDFDOI

• Transient rewilding alters the lung immunologic landscape enhancing host protective responses to helminth infection 3007

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Infection of laboratory-housed mice with the helminth N. brasiliensis (Nb) triggers lung inflammation, contributing to hemorrhaging and acute lung injury (ALI) followed by the development of a polarized type 2 pulmonary immune response and host protective macrophages. (Chen F et al, NI 2014, CR 2022). To examine whether exposure of mice to a rewilding environment might alter this response, mice were housed in an outdoor mesocosm reflecting a natural environment, for five weeks, after which they were returned to the lab and immediately infected with Nb. The RW mice showed a significantly lower worm burden at day 5 after infection. At day 2, increased ALI and lung hemorrhaging, was also significantly reduced.To examine potential changes in the lung immunologic landscape, scRNAseq was performed on rewilded WT and IL-4/IL-13-/- mice. RW WT mice showed significant increases in lung M2 macrophage activation, which was blocked in IL-4/IL-13-/- mice. Inoculation with microbiota isolated from RW mice, which includes Aspergillus species (Yeung F et al, CHM 2020), showed reduced worm burden, hemorrhaging and ALI after Nb infection. Inoculation with RW purified fungi A. fumigatus followed by Nb infection two weeks later showed similar host protective effects. These studies suggest that fungi acquired during transient rewilding can markedly alter pulmonary immune cell activation and function resulting in polarization towards type 2 inflammatory responses. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

  PublisherOA PDFDOI

• CD301b + DC-Dependent Innate Inflammation Ignites Type 2 Immunity Against Helminthinfection in the Lung

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Helminth infection favors persistent and proliferating alternatively activated neutrophils in the lung 2684

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Neutrophils are granulocytic myeloid cells that have critical effector functions during infectious disease but are typically thought to be short-lived, terminally differentiated phagocytic cells. We directly compared lung neutrophil activation following infection with different groups of pathogens including bacteria (Staphylococcus aureus), fungi (Aspergillus fumigatus), and helminths (Nippostrongylus brasiliensis) at 2 days after infection. Our results showed considerable heterogeneity depending on the type of infectious agent. Bulk RNAseq, EdU incorporation, and flow cytometric staining for necrosis/apoptosis identified distinct activation states with rapid cell death predominant in neutrophils after S. aureus and A. fumigatus infection, while neutrophils from helminth infected mice exhibited increased cell cycling and expression of signaling pathways associated with proliferation, type 2 responses, and wound healing. Spectral flow cytometry, intravascular staining, and scRNAseq revealed a distinct c-kit+ proliferating subset of lung neutrophils that expanded shortly after helminth infection and was released from the endothelial niche to co-localize with invading parasites in the airways. These findings challenge current models of neutrophil function during infectious disease, suggesting that neutrophils uniquely assume a persistent and proliferative phenotype that may contribute to tissue repair and resistance in the context of the type 2 pulmonary inflammatory response. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

  PublisherOA PDFDOI

• Architecture of the neutrophil compartment

  Nature · 2025-12-03 · 19 citations

  articleOpen access
  PublisherOA PDFDOI

• Dysregulated of monocyte function prior to liver transplant is associated with increased risk of post-transplant mortality 3930

  The Journal of Immunology · 2025-11-01

  articleOpen access

  Abstract Description Cirrhosis induces progressively severe immune dysfunction, which persists early after liver transplant (LT) and increases risk of morbidity and mortality both prior to and following LT. We have previously identified the Liver Immune Frailty Index (LIFI), a pre-LT biomarker panel (MMP-3 and Fractalkine), which stratifies patients into tertiles of risk for post-LT mortality. 1-yr post-LT mortality is 63% vs. 1.8% in LIFI-high and -low (c-statistic 0.83). Plasma and PBMCs were obtained at the time of liver transplant (T0) and stratified by LIFI (-low vs high/moderate). Bulk RNAseq demonstrates distinct gene expression profiles in LIFI-high/moderate vs LIFI-low. Notably, pathways related to toll-like receptors (TLRs) signaling and phagocytic activity were enriched, indicating innate immune involvement in pre-LT immune dysfunction. Single-cell RNAseq analysis of monocyte clusters identified CD14+ monocytes as major contributors to TLRs and pattern recognition receptors (PRRs) upregulation in T0 PBMCs. These changes could result from bacterial translocation due to cirrhosis-related increases in intestinal permeability and peripheral vasodilation prior to LT. Such increases in antigen presentation could trigger an excessive pro-inflammatory response by monocytes. Persistence of such monocyte dysregulation early after LT could contributing to ongoing immune dysfunction and increased susceptibility to infection, thus impacting risk of post-LT mortality. Funding Sources 1R01DK137222-01A1, 1R21AI180739-01A1 Topic Categories Transplantation Immunology (TRAN)

  PublisherOA PDFDOI

• Helminth protein enhances wound healing by inhibiting fibrosis and promoting tissue regeneration

  Life Science Alliance · 2024-08-23 · 11 citations

  articleOpen accessSenior authorCorresponding

  Skin wound healing due to full thickness wounds typically results in fibrosis and scarring, where parenchyma tissue is replaced with connective tissue. A major advance in wound healing research would be to instead promote tissue regeneration. Helminth parasites express excretory/secretory (ES) molecules, which can modulate mammalian host responses. One recently discovered ES protein, TGF-β mimic (TGM), binds the TGF-β receptor, though likely has other activities. Here, we demonstrate that topical administration of TGM under a Tegaderm bandage enhanced wound healing and tissue regeneration in an in vivo wound biopsy model. Increased restoration of normal tissue structure in the wound beds of TGM-treated mice was observed during mid- to late-stage wound healing. Both accelerated re-epithelialization and hair follicle regeneration were observed. Further analysis showed differential expansion of myeloid populations at different wound healing stages, suggesting recruitment and reprogramming of specific macrophage subsets. This study indicates a role for TGM as a potential therapeutic option for enhanced wound healing.

  PublisherOA PDFDOI

• Protocol for immunofluorescence staining of murine helminth-infected intestinal and lung tissues

  STAR Protocols · 2023-04-21

  articleOpen accessSenior authorCorresponding

  Preserving structurally intact tissue through proper tissue fixation and cryopreservation minimizes tissue autolysis, desiccation, and enzymatic degradation. In this protocol, we describe the use of an optimized fresh freezing technique that cryopreserves the tissue and favors the retention of the natural protein structure of antigens. We also detail the use of cold, low-concentration paraformaldehyde (PFA) fixation to enhance tissue morphology and detection of fluorescent proteins, such as GFP and TdTomato, in tissues of genetically engineered mice. For complete details on the use and execution of this protocol, please refer to Chen et al. (2022)1 and El-Naccache et al. (2022).2

  PublisherDOI

Recent grants

• Genesis of Defective Effector Lymphocytes in the Helminth-Coinfected Host

  NIH · $512k · 2016–2018

• NIH Grant U01AI032247

  NIH · $12.8M · 2005

• Induction of effector lymphocyte lethargy by helminth coinfection

  NIH · $2.9M · 2017–2023

• Innate type 2 immune mechanisms of resistance

  NIH · $1.6M · 2013–2017

• Protective and pathologic functions of macrophages induced by helminths

  NIH · $2.1M · 2017–2022

Frequent coauthors

• Wenhui Wu

  102 shared

• Joseph F. Urban

  101 shared

• Pankaj Kumar Mishra

  Rutgers, The State University of New Jersey

  88 shared

• Fei Chen

  84 shared

• Darine W. El-Naccache

  Rutgers New Jersey Medical School

  82 shared

• Zhugong Liu

  United States Food and Drug Administration

  64 shared

• Mark Palma

  Rutgers New Jersey Medical School

  62 shared

• Alexander Lemenze

  Rutgers New Jersey Medical School

  56 shared

Education

• B.A.

  University of Virginia

  1980

• Ph.D.

  Cornell University

  1986