"Investigating the function and regulation of ZU5-domain containing proteins"

Cornelius Taabazuing

Danger associated molecular patterns (DAMPS) are sensed by pattern-recognition receptors (PRRs) which in turn trigger the activation of proteases known as caspases that induce cell death. These receptors form large multiprotein complexes that serve as the activation platforms for caspases. Caspase-1 and caspase-2 are both activated on large multiprotein platforms by sensor proteins that belong to the ZU5-domain containing family of proteins. However, the molecular mechanism of how these ZU5 containing proteins activate their cognate proteases remains incompletely understood. Furthermore, the composition of the death platform influences the substrate repertoire of the caspases, but the factors that guide the substrate specificity as well as the substrates of caspases remain ill defined. The Taabazuing lab is interested in elucidating the molecular mechanism of how the ZU5-family of sensor proteins activate proteases to induce cell death. As the substrates of caspases regulate important biological functions, such as immunity, the lab is also interested in understanding the factors that guide substrate specificity and in identifying and characterizing novel caspase substrates. Importantly, we hope to leverage the mechanistic insights into novel therapies for human diseases.