Research projects

In this project, we will explore how different mutation positions dictate changes in their interacting partners and how such perturbations can be linked to clinical implications, focusing on p53 as our computational and experimental model. For meet this ambitious challenge, two highly complementary laboratories will synergise by combining their expertise: cancer genomics/ proteomics (Park, CNIO) and p53 research and cancer biology (Oren, WIS). Specifically, the Park team will develop a computational pipeline for prioritizing cancer driver mutations in TP53 (mutp53) from large-scale cancer genomics data and will perform a high-throughput screening for mutp53- specific protein-protein interaction (PPI) network. Predictions generated computationally by the Park team will be subjected to experimental validation by the Oren team, by interrogating specific PPI perturbations elicited by selected p53 mutants in human cancer cells. The Oren team will also explore the possibility that a small molecule inhibitor of a particular mutp53 PPI, identified through a high throughput drug screen, can serve as a mutant-specific anticancer agent. 

Although TP53 is the most frequently mutated gene in human cancer, targeting it for cancer therapy has proven extremely difficult. The in-depth understanding generated by the proposed project may suggest new strategies for designing p53-targetted treatments, with potentially huge social and economic impact.