Developing small molecules that target Bcl-2 pro-survival proteins

Through structure-based drug design of peptide-mimetic scaffolds, we develop small molecules that target protein-protein interactions. Specifically, our team is interested in developing compounds that interfere with binding between proteins of the BCL-2 family. Our targets of interest within this family are BCL-XL, MCL1 and BAX. The potential therapeutic applications of this work range from cancer to ischemia and reperfusion events.

Team members: Romina Lessene, George Nikolakopoulos, Michael Roy, Amelia Vom

Developing small molecules that inhibit apoptosis

Together with Professors Ben Kile and David Huang, we aim to identify small molecules that inhibit apoptosis. We have developed a powerful phenotypic assay that has delivered potent and specific inhibitors of mitochondrial apoptosis. Using these unique probe compounds we identified, we are investigating the regulation of pro-apoptotic protein BAK and assessing the impact of apoptosis inhibition in animal model of diseases in which excessive apoptosis has been implicated.

Team members: Yelena Khakham, Kate McArthur, Romina Lessene

Developing small molecule inhibitors of necroptosis

In collaboration with institute colleagues including Dr James Murphy and Associate Professor John Silke, we are developing a range of chemical probes that modulate necroptosis, a programmed form of cellular necrosis. As most of the intricacies of this pathway are still unknown, we aim to use our chemical probes to identify new protein components of this pathway, and to employ the most advanced compounds to validate necroptosis inhibition in inflammatory diseases.

Team members: Catia Pierotti, Christoph Grohmann, Wilco Kersten