Matthew I. McFadden

ORCID: 0009-0005-4955-7111
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About
Contact & Profiles
Research Areas
  • interferon and immune responses
  • Inflammasome and immune disorders
  • Immune Response and Inflammation
  • Immune cells in cancer
  • SARS-CoV-2 and COVID-19 Research
  • Melanoma and MAPK Pathways
  • Viral Infections and Immunology Research
  • Antioxidant Activity and Oxidative Stress
  • RNA regulation and disease
  • Fatty Acid Research and Health
  • Influenza Virus Research Studies
  • Cytokine Signaling Pathways and Interactions
  • Respiratory viral infections research
  • Eicosanoids and Hypertension Pharmacology

The Ohio State University
2023-2025

The Ohio State University Wexner Medical Center
2025

Abstract Influenza virus activates cellular inflammasome pathways, which can be both beneficial and detrimental to infection outcomes. Here, we investigate the function of inflammasome-activated, pore-forming protein gasdermin D (GSDMD) during infection. Ablation GSDMD in knockout (KO) mice ( Gsdmd −/− ) significantly attenuates influenza virus-induced weight loss, lung dysfunction, histopathology, mortality compared with wild type (WT) mice, despite similar viral loads. Infected exhibit...

10.1038/s41467-024-47067-0 article EN cc-by Nature Communications 2024-03-29

ABSTRACT Here we investigated whether interferon induced transmembrane protein 3 (IFITM3), a key antiviral deficient in certain human populations, affects interspecies adaptation of SARS-CoV-2. We found that SARS-CoV-2 Beta and Omicron variants passaged through IFITM3-deficient versus wild type mice exhibit enhanced replication pathogenesis this new host species. Enhancements associated with amino acid substitutions the viral genome, suggesting IFITM3 limits accumulation adaptive mutations....

10.1101/2025.01.27.635150 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2025-01-28

Cellular stress in the form of disrupted transcription, loss organelle integrity, or damage to nucleic acids can elicit inflammatory responses by activating signaling cascades canonically tasked with controlling pathogen infections. These stressors must be kept check prevent unscheduled activation interferon, which contributes autoinflammation. This study examines role transcription factor myocyte enhancing 2A (MEF2A) setting threshold transcriptional R-loop accumulation. Increases R-loops...

10.1016/j.celrep.2023.112805 article EN cc-by-nc-nd Cell Reports 2023-07-18

Ozone (O3) is an air pollutant that induces pulmonary inflammation and injury, leading to increased susceptibility exacerbation of chronic lung diseases. Furthermore, ambient O3 levels are expected rise with increasing global temperatures. Docosahexaenoic acid (DHA) omega-3 (n-3) polyunsaturated fatty (PUFA) primarily found in oily fish reduces enhances the resolution inflammation. This partially attributed DHA-derived oxylipins termed specialized pro-resolving mediators (SPMs) have...

10.1165/rcmb.2024-0586oc article EN American Journal of Respiratory Cell and Molecular Biology 2025-04-10

Seasonal influenza results in 3 to 5 million cases of severe disease and 250,000 500,000 deaths annually. Macrophages have been implicated both the resolution progression disease, but drivers these outcomes are poorly understood. We probed mouse lung transcriptomic datasets using Digital Cell Quantifier algorithm predict immune cell subsets that correlated with mild or A virus (IAV) infection outcomes. identified a unique macrophage population transcriptionally resembled small serosal cavity...

10.1073/pnas.2300474120 article EN cc-by-nc-nd Proceedings of the National Academy of Sciences 2023-12-15

Abstract Influenza virus activates cellular inflammasome pathways, which can be either beneficial or detrimental to infection outcomes. Here, we investigated the role of inflammasome-activated pore-forming protein gasdermin D (GSDMD) during infection. Ablation GSDMD in knockout (KO) mice significantly attenuated virus-induced weight loss, lung dysfunction, histopathology, and mortality compared with wild type (WT) mice, despite similar viral loads. Infected KO exhibited decreased...

10.1101/2023.03.08.531787 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2023-03-08

ABSTRACT Type III interferons (IFNλ) are innate immune cytokines that limit viral replication and coordinate tissue repair through the induction of interferon stimulated genes (ISGs). This response must be tightly regulated to avoid excessive responses result in disruption barrier integrity or inefficient allow for pathogen escape. Here we examine contribution Mitogen Activated Protein Kinase (MAPK) signaling on IFNλ-mediated antiviral activity. We find extracellular-signal-regulated kinase...

10.1101/2024.05.21.595218 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2024-05-24
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