Li-Yao Huang

Background

I completed my DPhil study in the laboratory of Prof. Catherine Pears at the University of Oxford in 2020.  My DPhil research focused on the role of H3K4me3-directed histone 3 acetylation (H3Ac) in the mechanism of action of TSA, a histone deacetylase inhibitor (HDACi). HDACis are approved for the treatment of multiple myeloma and T-cell lymphoma. However, the response rate was only ~30% and drug resistance emerged post-treatment. HDACi treatment leads to hyperacetylation of histone H3 that favours those with H3K4me3 mark, but the biological importance of this dynamic acetylation is unknown. Using Dictyostelium as a model organism, I revealed that mutations leading to loss of H3K4me3 confer loss of rapid H3 hyperacetylation and result in resistance to TSA during development. Using genetic, biochemical and cell-based assays I also unravelled Sgf29, a subunit of in the large SAGA acetyltransferase complex, as the mediator of H3K4me3-directed H3Ac.

Current research

My current research concerns a newly discovered synthetic lethal relationship between PLK4 inhibition and high expression of TRIM37, an E3 ligase. The gene coding for TRIM37 sits in chromosome 17q, a region that has been found amplified in a subset of breast cancers and in the majority of high-risk neuroblastoma. Cancer cells harbouring the 17q-ter amplification express a high level of TRIM37 and are highly sensitive to PLK4 inhibition. I am interested in identifying key positive and negative regulators involving in the TRIM37-PLK4i synthetic lethality.