Friday, May 9, 2025
5/9/2025
Cytosolic Immune Surveillance During Bacterial Infections - Inflammasomes sense an array of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) generated during infection and trauma and represent the first line of defense against infections. In the canonical form, inflammasomes consist of a sensor protein that recognizes PAMPs, an adaptor molecule ASC, and an effector protease, caspase-1. In the noncanonical form, inflammatory caspases related to caspase-1, namely caspase-11 and caspase-4, directly sense cytosolic lipopolysaccharide (LPS) from Gram- negative bacteria and their outer membrane vesicle. Inflammasome signaling culminates in the post-translational activation of IL-1β, IL-18, gasdermin D (a pore-forming protein), and pyroptosis, a lytic and inflammatory form of cell death, and the simultaneous release of DAMPs. Despite the profound implications of inflammasome responses in infections, cancer, and autoimmunity, the regulatory modules that fine-tune the initiation and termination of inflammasome signaling remain mostly unknown. This proposal seeks to comprehensively address this critical knowledge gap in three specific aims by focusing on galectins, a family of β-galactoside-binding proteins. Owing to their capacity to bind to N- or O-glycan termini of various glycoproteins and regulate their membrane localization and signal transduction, galectins have diverse functions in various physiological and pathological processes. Aims 1 and 2 of the proposal will investigate galectins' role in noncanonical inflammasome signaling in murine and human cells and in vivo. Aim 3 will explore how galectins control canonical inflammasome signaling in vitro and in vivo. In summary, the findings from this project would reveal new players in inflammasome signaling with significant implications for human infectious diseases and sepsis.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).