Dr Ben Croker
Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, School of Medicine, UCSD Center for Immunity, Infection, and Inflammation
University of California, San Diego
Contract research opportunitiesWe support the UCSD BSL-3 and ABSL-3 facilities for investigating COVID-19 and for modeling SARS-CoV-2 variants in mouse and human systems.
Ptpn6 inhibits caspase-8- and Ripk3/Mlkl-dependent inflammation. Nature Immunology 2019. https://www.nature.com/articles/s41590-019-0550-7
Ptpn6 negatively regulates p38 MAPK activation to control TNF and IL-1a/b expression, and maintains Ripk1 function to prevent caspase-8- and Ripk3–Mlkl-dependent cell death and concomitant IL-1a/b release.
Mor et al., Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors. PLOS Pathogens 2021, 17(2):e1009165. PMID:33571304
b-glucan dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment. PLoS Biol 2019, 17(9): e3000113. PMID: 3148377
Neutrophils transfer pathogens to macrophages in a novel process called shuttling.
Research ActivitiesWe 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:
- Research led by Dr. Akshay D’Cruz identified roles for MLKL-dependent lytic cell death pathways in neutrophil extracellular trap formation. PAD4 was shown to be activated downstream of MLKL, and was essential for generation of NETs but surprisingly was not required for chromatin condensation. This work has revealed entire new signaling pathways controlled by MLKL activation. Parallel studies of GSDMD-dependent canonical NET formation and non-canonical inflammasome activation provides a framework for neutrophil biologists to explore the relationship between non-apoptotic neutrophil cell death, NET generation, and responses to infection.
- We identified a novel Ptpn6 Y208N mutant mouse strain causing cutaneous inflammation of the feet. A research team led by Dr. Mary Speir has now demonstrated that mice carrying neutrophil-specific deletions of Ptpn6 develop neutrophilic dermatoses caused by MLKL- and Caspase-8-dependent inflammatory cell death driving IL-1 release.
- Our research supports ongoing efforts in the UCSD BSL-3 to understand the cytopathic effects of new mutant strains of SARS-CoV-2. We are working to characterize apoptosis pathways triggered by SARS-CoV-2 infection and the neutralizing activity of monoclonal antibodies. Our research uses new image analysis tools to track the spread of individual SARS-CoV-2 virions to neighboring cells.