Timeframe: 2025 – 2027
Goal: Investigate alternate means of therapeutically targeting DNAJ-PKAc
Principal Investigator: Yasemin Sancak, PhD
Study overview: This effort, led by Yasemin Sancak of the University of Washington, aims to study mitochondrial abnormalities in FLC. It has long been known that FLC cancer cells are filled with abnormal mitochondria, but the causes and implications of those mitochondrial changes are not understood. As the “energy factories” of a cell, mitochondria play central roles in metabolism. Recent work has highlighted the importance and impact of the metabolic shifts that occur in FLC, including changes in the urea cycle that can lead to dangerous levels of ammonia in FLC patients. The Sancak lab has determined that FLC mitochondria contain excess calcium and that those high calcium levels are directly driven by FLC’s DP-fusion protein. The goal of the effort is to understand the impact of mitochondrial calcium overload in FLC, how it drives changes in the urea cycle, and whether those changes can be mitigated by drug treatment. If the study is successful, new potential therapeutic targets could be identified.