Prof. Brian Liau
Title: Chemical Genomics: Small Molecule Mechanism in the Era of Large-scale Genetics
Abstract:
The orchestrated interactions of protein complexes shape cell function and state. Dysregulation of these complexes and their interactions can underlie human disease, and new therapeutic approaches to modulate them by blocking or even creating interactions with small molecules are transforming paradigms for drug discovery. Beyond their promise as therapeutics, small molecules are powerful tools to dissect the function and biology of protein complexes. But their full potential is only unlocked if we understand their mechanisms of action. By combining genome editing with small molecule profiling, we describe the systematic identification of drug resistance-conferring mutations across protein targets of interest. These mutations not only confirm on-target engagement but also act as discovery tools to uncover new biology and mechanisms through the serendipitous insights they can offer. In this seminar, I will describe how the application of these chemical genomic approaches in combination with deeper mechanistic investigation have reshaped our views on targeting chromatin complexes and their interactions with small molecules.
Bio:
Brian Liau is an associate professor in the Department of Chemistry and Chemical Biology at Harvard University. He obtained his bachelor’s degree in Chemistry and Physics from Harvard College, before receiving a PhD in Chemistry under the guidance of Dr. Matthew Shair. During his PhD studies, Brian completed the chemical synthesis of complex bioactive natural products and investigated their biological mechanism of action. As a postdoctoral fellow with Dr. Bradley Bernstein, he studied epigenetic mechanisms of adaptation and drug resistance in brain cancer. In 2016, Brian started his independent research group, which integrates chemical biology with genomics to unravel chromatin complexes and gene regulation. The Liau lab has pioneered chemical genomic approaches to systematically identify drug resistance-conferring mutations for protein drug targets, which they leverage in mechanistic studies to discover small molecule mechanism of action and new target biology.
Keywords: Chemical Biology, Small Molecules, Molecular Glues, Protein-Protein Interactions
Host: Prof. Helen Blackwell