Professor Brian Liau (Harvard University)

Title: Chemical Genomics: Small Molecule Mechanism in the Era of Genome Editing

Abstract: My laboratory combines breakthroughs in genome-editing technologies with fundamental strategies in chemical biology to uncover the mechanisms of small molecule therapeutics and their protein targets in human disease. The elucidation of small molecule mechanism has led to key inflection points in our understanding of biology and therapeutic modalities, often expanding our perspective of druggability. While genetics has long played a central role in these discoveries, advances in high-throughput genome editing have created new opportunities to explore small molecule mechanism through the systematic manipulation of proteins—in physiologically relevant contexts, and at a resolution and scale previously unattainable.

In this seminar, I will discuss how we integrate our knowledge of chemistry with genome editing to drive new insights using structure-activity relationships at both the chemical and macromolecular levels. We have focused these approaches on studying proteins aberrantly altered in cancer, leading to unexpected discoveries that challenge our views on how chemical and molecular interactions shape small molecule mechanism, protein function, and cancer vulnerabilities—ultimately informing therapeutic opportunities. More broadly, our efforts spearhead an emerging experimental paradigm that is rapidly changing the study of small molecules and protein function. Looking forward, we envision a general platform to combine chemical and genetic perturbations at scale, catalyzing the discovery of biological mechanisms and rational therapeutics development.

Biography: Brian Liau is the Morris Kahn 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 at Massachusetts General Hospital, he studied epigenetic mechanisms of adaptation and drug resistance in brain cancer. In 2016, Brian started his independent research group, which bridges chemical biology with functional genomics to investigate the molecular mechanisms underpinning human disease, protein function, and drug action. His lab’s contributions have been recognized by numerous awards, including the NIH Director’s New Innovator Award, Ono Pharma Breakthrough Science Initiative Award, Damon Runyon-Rachleff Innovation Award, American Cancer Society Research Scholar Grant, Camille Dreyfus Teacher-Scholar Award, Sloan Research Fellowship in Chemistry, Mark Foundation ASPIRE award, and the Eli Lilly Award in Biological Chemistry.