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Novel serine peptidases regulate the NLRP1 and CARD8 inflammasomes


EMSL Project ID
51488

Abstract

The inflammatory response provides an absolutely essential host defense mechanism that, if perturbed, can itself cause a large number of human diseases. Collectively, innate immune responses integrate a number of genome-encoded sensor proteins to combat threats such as pathogens and endogenous damage. Selected throughout multicellular evolution, these proteins recognize patterns of pathogen-specific molecules, such as bacterial flagellin and lipopolysaccharide, with remarkable sensitivity and selectivity. Following detection, host cells launch coordinated defensive measures through innate immune signaling pathways. Two such inflammasome sensors, NLRP1 and CARD8, express highly in skin and lymphocytes and activate in response to a myriad of signals that trigger their functional degradation. Here, we aim to extend our surprising biological findings (unpublished) to novel NLRP1 and CARD8 inflammasome regulators, PREP and PREP-L, whose functions themselves are poorly delineated. Elucidating the molecular basis of their function in inflammation will open new therapeutic windows in inflammatory diseases.

Project Details

Start Date
2020-06-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Hao Wu
Institution
Boston Children's Hospital

Team Members

Teerithveen Pasricha
Institution
Boston Children's Hospital

Shanon Lee
Institution
Boston Children's Hospital

Kelly Walter
Institution
Boston Children's Hospital

Pietro Fontana
Institution
Boston Children's Hospital

Humayun Sharif
Institution
Boston Children's Hospital

Louis Hollingsworth
Institution
Boston Children's Hospital

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory