This research project focuses on understanding how inflammatory caspases, particularly caspases 4 and 5 in humans and caspase 11 in rodents, regulate the protein translation machinery during pyroptosis. Previous studies have identified gasdermin D (GSDMD) as a substrate for these caspases; however, our hypothesis suggests additional substrates may exist, particularly among proteins involved in translation. Using an artificial amino acid engineering system, we have identified several potential caspase-4 substrates, including eukaryotic initiation factors. We aim to confirm whether these proteins are direct targets of caspase-mediated cleavage during pyroptosis. By identifying new caspase substrates, this research could provide critical insights into how inflammatory responses suppress protein synthesis, potentially uncovering novel therapeutic targets for diseases involving chronic inflammation.
Northeastern University
