Meng-Ju Wu to Study How Mutations in IDH1 Reprogram Cancer Cells to Evade Immune Detection 

Meng-Ju Wu, PhD, assistant professor of medicine in the Division of Gastroenterology, has been awarded an NIH K22 Transition Career Development Award for his project titled “Deciphering the Immune Evasion Mechanisms in Mutant IDH1 Cancer.” This research investigates how mutations in the metabolic enzyme IDH1, commonly found in intrahepatic cholangiocarcinoma (ICC) and glioma, reprogram cancer cells to evade immune detection and resist therapy. Dr. Wu previously discovered that the oncometabolite 2-hydroxyglutarate (2HG), produced by mutant IDH1, suppresses innate immune signaling by epigenetically silencing the DNA sensor cGAS. His work showed that pharmacologic inhibition of IDH1 can restore viral mimicry responses and reinvigorate CD8+ T cell activity. Building on this foundation, the K22 project explores two key immune evasion strategies in IDH1-mutant tumors: tumor-intrinsic epigenetic repression of innate immune sensors and metabolic crosstalk by which 2HG impairs T cell and macrophage function. 

Beyond IDH1 biology, Dr. Wu’s lab is deeply committed to understanding cholangiocarcinoma, a highly lethal and understudied liver cancer. Using a powerful platform of genetically engineered mouse models and patient-derived cell lines and organoids with common driver mutations (such as IDH1, KRAS, FGFR2, and BAP1), his team aims to uncover the fundamental mechanisms of this dismal disease and translate insights into novel therapeutic strategies. Dr. Wu’s research holds promise not only to advance understanding of cancer metabolism and immune evasion but also to develop urgently needed cholangiocarcinoma therapies.