Ruida Hou, MD, PhD

Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with relapses remaining a major cause of treatment failure. We are investigating a new strategy that targets dihydroorotate dehydrogenase (DHODH), an enzyme critical for both DNA biosynthesis and mitochondrial energy generation. These processes are uniquely essential for leukemia cells. Using genome-wide CRISPR screening, we discovered that blocking salvage DNA production pathways can make leukemia cells highly vulnerable to DHODH inhibition, while defects in mitochondrial energy complexes can cause resistance. Our project combines large-scale patient data analysis with laboratory and animal studies to identify which patients are most likely to respond and to develop drug combinations that prevent resistance. This work aims to deliver more precise, effective treatments that could improve survival and reduce relapse in children with ALL.