About

Our lungs experience challenges daily from environmental exposures such as air pollutants, particulate matter, noxious gases, allergens, viruses, and bacteria. The central focus of our lab is to identify and investigate novel mechanisms of environmental exposures and how they can lead to pulmonary pathogenesis. Specifically, we wish to elucidate the pathways in which environmental exposures alter the pulmonary immune response since this makes the lung more susceptible to infection. Lastly, our interests also lie in determining how diet can be used to alter the pulmonary immune response to prevent infectious and inflammatory lung diseases.

Research topics

• Medicine
• Biology
• Pathology
• Intensive care medicine
• Internal medicine
• Ecology
• Gerontology
• Genetics
• Environmental health

Selected publications

• Tissue-Resident Alveolar Macrophages Reduce Ozone-induced Inflammation via MerTK-mediated Efferocytosis.

  UNC Libraries · 2026-04-21

  articleOpen access

  Lung inflammation, caused by acute exposure to ozone (O₃), one of the six criteria air pollutants, is a significant source of morbidity in susceptible individuals. Alveolar macrophages (AMØs) are the most abundant immune cells in the normal lung, and their number increases after O₃ exposure. However, the role of AMØs in promoting or limiting O₃-induced lung inflammation has not been clearly defined. In this study, we used a mouse model of acute O₃ exposure, lineage tracing, genetic knockouts, and data from O₃-exposed human volunteers to define the role and ontogeny of AMØs during acute O₃ exposure. Lineage-tracing experiments showed that 12, 24, and 72 hours after exposure to O₃ (2 ppm) for 3 hours, all AMØs were of tissue-resident origin. Similarly, in humans exposed to filtered air and O₃ (200 ppb) for 135 minutes, we did not observe at ∼21 hours postexposure an increase in monocyte-derived AMØs by flow cytometry. Highlighting a role for tissue-resident AMØs, we demonstrate that depletion of tissue-resident AMØs with clodronate-loaded liposomes led to persistence of neutrophils in the alveolar space after O₃ exposure, suggesting that impaired neutrophil clearance (i.e., efferocytosis) leads to prolonged lung inflammation. Moreover, depletion of tissue-resident AMØs demonstrated reduced clearance of intratracheally instilled apoptotic Jurkat cells, consistent with reduced efferocytosis. Genetic ablation of MerTK (MER proto-oncogene, tyrosine kinase), a key receptor involved in efferocytosis, also resulted in impaired clearance of apoptotic neutrophils after O₃ exposure. Overall, these findings underscore the pivotal role of tissue-resident AMØs in resolving O₃-induced inflammation via MerTK-mediated efferocytosis.

  PublisherDOI

• Heterogeneous Causes of Acute Respiratory Distress Syndrome Correlate With Distinct Peripheral Polyunsaturated Fatty Acid Metabolites

  The FASEB Journal · 2026-05-13

  articleOpen accessSenior author

  Acute Respiratory Distress Syndrome (ARDS), a heterogeneous syndrome of hypoxic respiratory failure secondary to dysregulated pulmonary inflammation, is caused by diverse insults. This heterogeneity presents challenges for mechanistic and therapeutic research, as evidenced by conflicting results from trials of n-3 polyunsaturated fatty acid (PUFA) supplementation for ARDS. PUFAs and downstream oxylipins are important to pulmonary inflammation but are not well defined in ARDS. We hypothesized that differences in fatty acid metabolism, as measured by levels of n-3 and n-6 PUFAs and oxylipins, are associated with differences in ARDS outcomes, inflammation, and causes. To test this, PUFAs/oxylipins were measured by LC MS/MS in plasma samples from 90 patients with ARDS. Pro-inflammatory cytokines and chemokines IL-6 and IL-8 were measured by ELISA. Multivariable linear regressions modeled the relationship between PUFAs/oxylipins, inflammation, and ARDS mortality, severity, and cause. Multiple n-3 and n-6 PUFA-derived oxylipins were decreased in severe ARDS. We did not detect differences in PUFAs/oxylipins by mortality. PUFAs/oxylipins varied by cause of ARDS, especially between patients with sepsis and those with trauma. Furthermore, specific oxylipins were associated with IL-6 and IL-8. As we observed that oxylipins varied by disease severity and underlying cause, these metabolites may function as biomarkers and suggest dysregulated mechanisms of lung repair. Furthermore, while oxylipins are derived from PUFAs, differences in PUFAs did not directly correlate with changes in oxylipins, suggesting altered lipid metabolism as a mechanism. Further consideration of differences in lipid metabolism in ARDS could identify subgroups with differential responses to n-3 PUFA supplementation or other therapies.

  PublisherOA PDFDOI

• 29 Antibacterial effects of the MEK1/2 inhibitor ATR-002 on Staphylococcus aureus

  Journal of Clinical and Translational Science · 2026-04-01

  articleOpen access

  Objectives/Goals: Pulmonary infections by Staphylococcus aureus (S. aureus) are difficult to eradicate in people with cystic fibrosis (CF, PwCF) and remain a significant disease burden. Our objective is to determine if a MEK1/2 inhibitor, ATR-002, can reduce S. aureus biofilm growth and synergize with antibiotics against multidrug-resistant strains of S. aureus. Methods/Study Population: To quantify the ability of ATR-002 to synergize with antibiotics, synergy checkerboard assays examined the effects of ATR-002 in combination with n=11 different antibiotics against the methicillin-resistant S. aureus (MRSA) strain USA300. We next quantified bacterial growth of n=6 antibiotic-resistant CF clinical isolates treated with a combinatory dose of 5 uM ATR-002 and antibiotic to confirm results from the checkerboard assay. Finally, S. aureus biofilms were established using USA300 or n=7 different CF clinical isolates in 96-well plates for 24 hours and then were treated with media, vehicle controls, or ATR-002 (5, 25, or 50 uM) for an additional 24 hours; bacterial biomass was quantified by crystal violet staining to assess the ability of ATR-002 to decrease biofilm growth. Results/Anticipated Results: Synergy checkerboard assays revealed that ATR-002 can synergize with the antibiotics gentamicin and amikacin, but had additive/indifferent effects with clindamycin, erythromycin, nafcillin, vancomycin, doxycycline, daptomycin, sulfamethoxazole-trimethoprim, linezolid, and puromycin. Additionally, two gentamicin/amikacin-resistant CF isolates were resensitized to gentamicin and amikacin with the addition of 5 uM ATR-002. However, CF isolates resistant to erythromycin, clindamycin, and nafcillin could not be resensitized to antibiotics with the addition of 5 uM ATR-002. Biofilms produced by MRSA, and n=3 out of 7 CF clinical isolates tested were significantly reduced by treatment of 50 uM ATR-002. Discussion/Significance of Impact: Our results demonstrate that ATR-002 can synergize with some antibiotics against MRSA, which is also observed in antibiotic-resistant CF S. aureus clinical isolates, and that ATR-002 can reduce established S. aureus biofilms. Future studies will explore the antibacterial effects of ATR-002 in additional clinically relevant models of infection.

  PublisherOA PDFDOI

• Review for "Oxidized phospholipid damage signals as modulators of immunity"

  2025-05-06

  peer-review1st authorCorresponding
  PublisherDOI

• SARS-CoV-2 innate immune recognition and implications for respiratory health

  Cytokine & Growth Factor Reviews · 2025-10-28 · 8 citations

  articleOpen access

  The ongoing global health impact of SARS-CoV-2, particularly on lung and respiratory health, underscores the critical need to decipher the intricate interplay between the virus and the host innate immune system. This review provides an analysis of the key pattern recognition receptors (PRRs) involved in SARS-CoV-2 recognition within the lung, including toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), and C-type lectin receptors (CLRs). We discuss how the engagement of these innate sentinels triggers crucial downstream consequences, ranging from protective antiviral interferon (IFN) responses to detrimental hyperinflammation characteristic of severe COVID-19. Numerous studies have identified sophisticated mechanisms employed by SARS-CoV-2 to evade or suppress early IFN induction, contributing to unchecked viral replication and subsequent immunopathology. We explore how this aberrant innate immune response drives the "cytokine storm", leading to acute respiratory distress syndrome (ARDS) and long-term sequelae. Furthermore, this review critically assesses current and emerging therapeutic strategies aimed at modulating innate immunity, including TLR agonists/antagonists, RIG-I/MDA5 modulators, NLRP3 inflammasome inhibitors, and IFN-based therapies, highlighting their potential and associated challenges. Finally, we identify key research gaps, emphasizing the need for cell-type-specific PRR studies, comprehensive mapping of viral evasion mechanisms, and the development of precision immunotherapies to enhance protective responses and mitigate pathogenic inflammation for future respiratory viral threats.

  PublisherDOI

• Author Correction: Profibrotic monocyte-derived alveolar macrophages are expanded in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19

  Nature Immunology · 2025-01-07 · 1 citations

  erratumOpen access
  PublisherOA PDFDOI

• Ultrafine particles and the disruption of resolution: Mechanistic insights into environmental lung disease

  Journal of Allergy and Clinical Immunology · 2025-11-20

  article
  PublisherDOI

• Examining the Interaction between Allergic Asthma and Air Pollution: a Potential Role for Trained Immunity

  Current Allergy and Asthma Reports · 2025-12-01

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Dietary Eicosapentaenoic Acid Improves Ozone-Induced Pulmonary Inflammation in C57/BL6 Mice

  UNC Libraries · 2025-11-12

  articleOpen access
  PublisherDOI

• Genetic deletion of <i>Alx/Fpr2</i> differentially regulates pulmonary inflammation in the absence and presence of acute lung injury

  ImmunoHorizons · 2025-09-17 · 3 citations

  articleOpen access

  The inflammation resolution receptor lipoxin A4/formyl peptide receptor 2 (ALX/FPR2) plays a critical role in immune regulation by binding select oxylipins derived from n-6 and n-3 polyunsaturated fatty acids (PUFAs). While ALX/FPR2 is implicated in controlling inflammation initiation and resolution, its specific role in pulmonary inflammatory responses remains unclear. In this study, we investigated how genetic deletion of Alx/Fpr2 controls oxylipin levels, immune cell populations, and inflammatory cytokines under conditions of homeostasis and injury. Alx/Fpr2 knockout (KO) mice exhibited normal food intake and weight gain but showed impaired glucose and lipid metabolism. Targeted lipidomic analyses by liquid chromatography-tandem mass spectrometry revealed elevated pulmonary concentrations of n-6 and n-3 PUFA-derived oxylipins in KO mice compared to controls. Flow cytometry further demonstrated increased lung infiltration of NK cells, monocytes, and lymphoid cells, indicating a proinflammatory state in the absence of injury. Following 24 h of LPS-induced acute lung injury, IL-1β levels were elevated in KO mice, but pulmonary histopathology, immune cell numbers, and oxylipin levels were comparable to those of controls. These results suggested a protective role of ALX/FPR2 upon acute lung injury, which led us to further investigate the role of ALX/FPR2 upon 72 h of lung injury. Indeed, Alx/Fpr2 KO mice showed reduced bronchoalveolar lavage protein concentration and lower levels of IL-6 and TNF-α. Collectively, these findings demonstrate that ALX/FPR2 deficiency promotes basal pulmonary inflammation but protects against prolonged injury-induced inflammation, highlighting the context-dependent role of this receptor in pulmonary inflammation.

  PublisherOA PDFDOI

Recent grants

• Novel role for CD163 in ozone induced alterations of pulmonary immunity

  NIH · $2.7M · 2018–2024

• Cell Sorter Grant for ECU Flow Cytometry Core Facility

  NIH · $509k · 2016–2017

• Dietary DHA mitigates ozone induced pulmonary inflammation

  NIH · $2.9M · 2020–2026

Frequent coauthors

• Michael B. Fessler

  Triangle

  74 shared

• Jennifer H. Madenspacher

  National Institute of Environmental Health Sciences

  53 shared

• Scott M. Palmer

  Clinical Research Institute

  35 shared

• Tereza Martinu

  University of Toronto

  32 shared

• Brita Kilburg‐Basnyat

  31 shared

• Kathleen M. Azzam

  National Institutes of Health

  27 shared

• Julia L. Nugent

  University of Oxford

  27 shared

• Sky W. Reece

  27 shared

Labs

• Gowdy Environmental Lung LabPI

  Investigating how environmental exposures can increase susceptibility to infection and how diet can be used to alter the pulmonary immune response.