Brian Liau earns award for novel approach to cancer research

January 22, 2020
Brian Liau stands in his lab, smiling broadly

Liau is one of 12 early career researchers honored for fighting cancer through innovation

 

On Tuesday, the Damon Runyon Cancer Research Foundation announced the 2020 winners of the Damon Runyon-Rachleff Innovation Award. Only a dozen United States-based early career researchers won the prize, which comes with initial grants of $400,000 over two years and the opportunity to receive two additional years. The Foundation supports faculty whose projects "have the potential to significantly impact the prevention, diagnosis and treatment of cancer."

Brian Liau, an assistant professor of chemistry at Harvard, recently made a significant breakthrough in determining why certain cancer treatments don't work for some patients. He focused in particular on acute myeloid leukemia (AML), which the American Cancer Society predicts will kill 11,000 people in the U.S. in 2019. 

Liau's new technique  — called CRISPR-suppressor scanning  — combines CRISPR scanning, a form of gene editing, with small-molecule profiling (a way to screen numerous drug molecules in one go), to investigate how current drugs interact with the malfunctioning genes they target. He and his team systematically identified mutations in LSD1, a critical protein in AML, and in doing so exposed details about the relationship between cells and the drugs used on them, knowledge that may one day lead to faster, more targeted treatments for all cancer patients.

But Liau didn't stop there. The Damon Runyon-Rachleff Innovation Award recognizes his creative approach to another potential path to treat AML. One form of enzyme regulation called allostery is critical for the body to interpret different biochemical signals to change enzyme structure, activity and function. Errors translating those signals into action can encourage cancer cells to grow.

By once again combining chemical biology and genome-editing methods, Liau is pioneering approaches to explore allostery, specifically focusing on DNA methyltransferase enzymes. These enzymes are often disrupted in cancers, including acute myeloid leukemia (AML), but their regulation is not understood. If Liau can identify the allosteric mechanisms that regulate DNA methyltransferase function, he could determine the impact of cancer mutations on enzyme function and, in time, design drugs to modulate their activity. This is only a first step: Liau can use this base knowledge to study all forms of cancer and help develop more efficient and effective treatments.