Principal Investigator: Prof. Lukasz Jaremko
Poster Presenter: Kacper Szczepski
Lab: MD3 Lab
Preserving genomic stability stands as a critical factor ensuring cell survival. Achieving this involves proper DNA replication, accurate gene transcription, and effective genome condensation. The regulation of genome condensation is, in part, controlled by post-translational modification (PTM) of the N-terminal tails of the histones including acetylation, phosphorylation, methylation and ubiquitination. Anomalies in PTMs patterns can lead to disruptions in gene expression that impact the entire cell cycle and often precede diseases such as cancer. Therefore, restoration of native epigenetic landscape can be viewed as a promising target therapy, both for treatment and reversibility of drug resistance. Here, we focus on histone 3, lysine 36 (H3K36) methyltransferases (KMTs), primarily NSD2 and NSD3, that regulate oncogenic transcriptional programs. We have investigated their gain-of-function (GOF) missense tumour driving mutations and gained insight into mechanisms driving the methylation hyperactivity. Understanding these mechanisms provides valuable guidance for designing novel chemical compounds – epidrugs, that could regulate epigenetic changes associated with particular cancers.