Charles Gersbach, PhD

A chemical engineering background is an indirect pathway to biomedical engineering, but for Dr. Charles Gersbach, the combination further ignited his passion for problem solving. As an Oxford-Harrington Rare Disease scholar, he hopes to translate next-generation CAR T cells to end Hodgkin Lymphoma (HL), a lymphatic cancer faced by almost 9,000 new patients each year.

“My PhD focused on applying engineering principles to building, restoring or regenerating damaged or diseased tissues,” Dr. Gersbach begins. “I loved asking questions like, if we want to treat disease, what do we have to change inside tissues? What is driving the cells to function abnormally? Which molecules are involved, and what parts of our DNA are encoding the relevant genes? Then, how do all those different genomic regions coordinate to result in disease?”

More recently, Dr. Gersbach began exploring epigenetics—the changes to genome structure that control genes turning on and off—and scrutinizing subtle mechanisms of gene expression that ultimately lead to disease. Using sophisticated high-throughput genetic screens, the Gersbach Lab made a novel discovery—overexpressing a single transcription factor called BATF3 (Basic Leucine Zipper ATF-Like Transcription Factor 3) reprograms T cells and enables them to keep killing cancer instead of succumbing to exhaustion or becoming unresponsive.

Dr. Gersbach is applying this knowledge in animal models to see how upregulating BATF3 expression improves the activity of T cells targeting of the CD30 protein, a marker highly selective for HL cells. The approach could prevent relapse and T cell exhaustion in HL patients treated with CAR T cell therapies. Of the HL patients treated with first generation CD30-targeted CAR T therapies, ~80% see their cancer progress in under two years. Dr. Gersbach and his team hope to reduce that statistic dramatically by arming T cells to keep circulating and protecting.

“We are manipulating the regulation of a genome in a way that can lead to more successful therapies and human clinical trials.”