Dr. Hongming Chen, Prof. Christian Ottmann, Dr. Helen Boyd
Characterization of 14-3-3 PPI and identification of isoform-specific small molecule modulators.
About the project:
The aim of my PhD project is to evaluate the druggability of 14-3-3 and its binding partners through the identification and development of small molecular modulators for 14-3-3 interaction with p53. 14-3-3 proteins are positive regulators of the tumor suppressor protein p53, the mutation of which is implicated in many human cancers. Current therapeutic strategies for targeting p53 mainly involve inhibition of the interaction with MDM2, its key negative regulator. However, the alternative approach of stabilizing the interaction of p53 with 14-3-3 proteins, its positive regulators, has not yet been explored. The discovery of small-molecules stabilizing 14-3-3/p53 interaction would potentially offer a novel mechanism of modulating dysfunctional p53 in tumor cell.
I was born in a small town in South of Estonia. I graduated from the University of Tartu with a Master’s degree in Chemistry in 2015. During my studies, I became interested in drug discovery and design. I’m doing my PhD at AstraZeneca in Gothenburg, where I can fulfill my dream of working in a pharmaceutical company.
Eindhoven University of Technology (6 months)
List of publications:
Adoption of a Turn Conformation Drives the Binding Affinity of p53 C-Terminal Domain Peptides to 14-3-3σ. Kuusk A, Neves JF, Bravo-Rodriguez K, Gunnarsson A, Ruiz-Blanco YB, Ehrmann M, Chen H, Landrieu I, Sanchez-Garcia E, Boyd H, Ottmann C, Doveston RG; ACS Chem. Biol.(2020) 15, 1, 262-271. DOI: 10.1021/acschembio.9b00893
Small-molecule stabilization of the p53 – 14-3-3 protein-protein interaction. Doveston RG, Kuusk A, Andrei SA, Leysen S, Cao Q, Castaldi MP, Hendricks A, Brunsveld L, Chen H, Boyd H and Ottmann C; FEBS Letters, 2017 Aug; 591 (16):2449-57;
List of posters:
Stabilization of 14-3-3-p53 protein-protein interaction. Kuusk A, Doveston RG, Andrei S, Neves JF, Rodriguez KB, Chen H, Boyd H, Ottmann C; EMBO Chemical Biology Conference, EMBL Heidelberg, Germany 29 Aug - 1 Sep 2018
List of presentations:
Chemistry Innovation Centre