A framework designed for discovery
Overview
This project combines biochemical, structural, and cell-based approaches in human cells to uncover the mechanisms by which canonical and non-canonical inflammasomes activate caspases and generate pro-inflammatory cytokines, with the goal of identifying novel therapeutic targets for inflammasomopathies.
Experimental / Computational Methods
Peptide-based caspase inhibitor development and specificity profiling; mechanistic studies of caspase-4/5 activation of pore-forming proteins and downstream caspase-1 activation; characterization of a human-specific LPS-sensing receptor in the absence of caspase-4/5; computational identification of a cryptic pocket on caspase-1 in collaboration with the Bowman lab; and FDA-approved small molecule library screening targeting identified cryptic pockets.
Data Sources / Models Used
Human cell-based inflammasome activation datasets; caspase inhibitor specificity profiling data; mechanistic datasets characterizing caspase-4/5 pore-forming protein activation and downstream cytokine release; structural and computational datasets identifying the caspase-1 cryptic pocket; and FDA-approved drug library screening data.
Analytical / Translational Focus
Elucidation of human-specific inflammasome activation mechanisms and identification of novel therapeutic targets — including a cryptic caspase-1 pocket and a human-specific LPS receptor — with translational goals including small molecule drug development for autoinflammatory disorders and sepsis. Findings underscore the necessity of human cell models for inflammasome research and have broad implications for therapeutic development across inflammasomopathies.
Powering the science
Cornelius Y. Taabazuing, PhD, Colton Consortium Member
Presidential Assistant Professor, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania