CROKER LAB
Department of Pediatrics, UC San Diego
Featured Topics
October 2026 Issue Cover:
We show that the pore-forming proteins GSDMD and GSDME cooperatively contribute to neutrophil-mediated inflammation in the autoinflammatory syndrome CAPS. The images are 3D renderings of activated neutrophils showing clusters of GSDMD (yellow) and GSDME (magenta) in the basal region.
RESEARCH
The life and death of neutrophils
We are an inflammation laboratory with a broad interest in the intersection of cell death, neutrophil biology, and innate immunity. Here are some of our recent research programs which seek to understand the pathophysiology of human inflammatory diseases:
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Clusters of the pore-forming proteins GSDMD and GSDME in neutrophils from the autoinflammatory syndrome CAPS control IL-1b secretion and inflammatory lytic cell death.
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As part of a U19 grant, we investigate host-pathogen interactions in Coccidioidomycosis, also known as Valley Fever. This soil-borne fungal pathogen causes chronic respiratory disease and in severe cases disseminated disease. Our research demonstrates that fungal sensing by Clec7a-TLR2 and the dual pyrin-NLRP3 inflammasomes triggers GSDMD-GSDME and MLKL activation, and IL-1b secretion from neutrophils and macrophages.
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We identified roles for GSDME- and MLKL-dependent cell death in neutrophil extracellular trap formation. PAD4 is activated in response to plasma membrane disruption by GSDME and MLKL, and is essential for generation of NETs. Parallel studies of GSDMD-dependent NET formation and non-canonical inflammasome activation provides a genetic framework to explore the relationship between apoptotic and non-apoptotic neutrophil cell death, NET generation, and responses to infection.
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We identified a novel Ptpn6 Y208N mutant mouse strain causing cutaneous inflammation of the feet. Mice carrying neutrophil-specific deletions of Ptpn6 develop neutrophilic dermatoses caused by MLKL- and Caspase-8-dependent inflammatory cell death driving IL-1 release.
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A clinical study of patients with Kawasaki disease and the COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) identified IL-1b+ neutrophils as a key immune cell targeted by intravenous immunoglobulin using a novel cell death pathway dependent on PI3-kinase and NADPH oxidase.