Dr. Dalia Barsyte-Lovejoy
Associate Professor, University of Toronto St. George, Department of Pharmacology & Toxicology & Principal Investigator, Structural Genomics Consortium
PI: Prof. Mark Currie
12 to 1 PM
IB 140 & Zoom
Title
Chemical biology and new ligand discovery in epigenetics and ubiquitin signaling
Abstract
Advances in human genome and disease modeling have brought forward novel disease targets. However, the majority of current small-molecule-based drug development is focused on a small set of proteins that are well within the established druggable proteome. Chemical probes are open-access tool compounds that enable the discovery of targets and the pharmacological modulation of diverse protein families, such as epigenetic enzymes, deubiquitylases, and E3 ligases. Using chemical probes, we uncovered the role of chromatin regulator histone methyltransferases NSD2 and EZH2 in blood cancers and identified transcriptome modulation by protein arginine methylation in immune cells.
To expand the druggable target space and enable degrader compounds with target pharmacology beyond inhibition, new compound screening methodologies such as DNA-encoded chemical library selection, followed by machine learning to predict ligands from virtual libraries, and an enantioselective protein affinity selection mass spectrometry screening approach are generating selective ligands for diverse protein family targets with unprecedented throughput and sensitivity. These new chemical biology tools will contribute to advancing drug discovery and understanding the complex biological underpinnings of disease.