My research interest is in the role of cancer-associated mutations in the metabolic enzyme, isocitrate dehydrogenase (IDH), which is common in intrahepatic cholangiocarcinoma (ICC) and are thought to act largely by interfering with chromatin regulation.
During my postdoctoral studies, I have concentrated on the biology of IDH mutant cholangiocarcinoma. I have generated a series of novel genetically engineered mouse models of cholangiocarcinoma harboring mutations in IDH1 in combination with different oncogene/tumor suppressor mutations found in the human disease. I have used these models to define the molecular circuits deregulated by IDH1 mutations and to investigate the biological and molecular impact of IDH inhibition. My work has revealed that tumor cells respond by both undergoing differentiation toward a hepatocyte lineage and by turning on immune stimulatory signaling.