Northwestern University Feinberg School of Medicine

Karen Ridge Lab

About Our Lab

Our research interests focus on defense against and recovery from viral pneumonia caused by severe influenza. We aim to identify the molecular signaling that modulates the transition from the initial phases of acute lung injury to the later phases of resolution and repair. A crucial step in the immune response to influenza A virus (IAV) is activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and subsequent secretion of pro-inflammatory cytokines. We reported that inhibition of the NLRP3 inflammasome with the small molecule inhibitor MCC950, beginning 3 days after infection, improves survival in IAV-infected mice. We were the first to report that the intermediate filament protein vimentin is required for assembly and activation of the NLRP3 inflammasome, and we have shown that vimentin knockout mice are protected from LPS-induced lung injury via suppression of the inflammasome. Furthermore, we have shown that vimentin knockout mice have a dampened pro-inflammatory cytokine response during IAV infection, which is associated with enhanced tissue repair and increased survival. We demonstrated that the initial lung injury in IAV infection is caused by monocyte-derived alveolar macrophages (MoAMs), and that treatment with an anti-CCR2 antibody to prevent MoAM recruitment to the lung reduces mortality in mice. Our preliminary data suggest that vimentin-deficient MoAMs exhibit a dampened inflammatory response and an enhanced pro-repair function in a cell-autonomous manner following IAV-induced lung injury. Our data also suggest that vimentin-deficient regulatory T cells (Tregs) exhibit a cell-autonomous pro-recovery function following acute lung injury.

Collaborators

G.R. Scott Budinger, MD
Chief of Pulmonary and Critical Care in the Department of Medicine, Ernest S. Bazley Professor of Airway Diseases, Professor of Medicine (Pulmonary and Critical Care) and Cell and Developmental Biology

Vladimir I. Gelfand, PhD
Leslie B. Arey Professor of Cell, Molecular, and Anatomical Sciences, Professor of Cell and Developmental Biology

Robert Goldman, PhD
Professor of Cell and Developmental Biology and Medicine (Pulmonary and Critical Care)

Alexander Misharin, MD, PhD
Assistant Professor of Medicine (Pulmonary and Critical Care)

Jacob I. Sznajder, MD
Ernest S. Bazley Professor of Asthma and Related Disorders, Professor of Medicine (Pulmonary and Critical Care) and Cell and Developmental Biology

Karen M Ridge, PhD

Karen M Ridge, PhD
Professor of Medicine (Pulmonary and Critical Care) and Cell and Molecular Biology

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