About our research interests
Our research focuses on the functional Roles and Regulation of Inflammatory Caspases in Diseases, including Cancers and Host Defense against Infection.
Caspases are a family of cysteine proteases that may be divided into two groups, the apoptotic caspases and the inflammatory caspases. The inflammatory caspases (human Caspase-1, -4 and -5) have gained prominence for their critical role in mediating innate immune responses. Caspase-1 is the best characterised inflammatory caspase to date. It is activated within inflammasomes (large cytosolic multi-protein complexes) by a growing number of PAMPs and DAMPs (pathogen/danger associated molecular patterns). Once activated, Caspase-1 is responsible for the processing and activation of the potent pro-inflammatory cytokines IL-1beta and IL-18. In contrast to caspase-1, caspases-4 and -5 are less well characterised in terms of their processing, activation and function. Caspase-5 is present in the NLRP1 inflammasome, whereas caspase-4 has yet to be found within an inflammasome complex.
Specific areas of interest include:
1. Elucidating the functional roles for caspases-4 and -5 via identification of their physiological substrates.
We are currently working on a novel substrate of caspases-4 and -5 which implicates these inflammatory proteases with a specific role in host defence against bacterial infection.
2. Identification of novel binding partners for caspase-1 and determining the implications of these interactions.
In addition to its role in the maturation of IL-1 beta and IL-18, other functions for caspase-1 have been reported, such as its role in pyroptosis (a form of cell death). We have identified the Rab GTPase, Rab39a, as a novel trafficking adaptor linking caspase-1 to IL-1beta secretion. Rab39a was identified by a proteomic screen for caspase-1 binding proteins in the human monocytic THP-1 cell line. During this screen a number of other potentially exciting caspase-1 interactors were identified and are currently being investigated.