FCF has awarded a grant for additional studies to be conducted by John Scott, PhD of the University of Washington in Seattle. As the Chair of the Department of Pharmacology, Dr. Scott has been a key leader of a multi-disciplinary team working on FLC at the University of Washington and the Fred Hutchinson Cancer Center in Seattle. This current grant is a renewal of a grant initially awarded by FCF in 2019.
FLC results from the activation of PKA. This usually occurs because of a gene fusion that produces an abnormal enzyme in which a critical segment of heat shock protein 40 (DNAJ) replaces a small segment of the PKA’s active subunit (PKAc). During the previous FCF-funded work, the Scott lab team asked how the DNAJ-PKAc fusion kinase altered activities compared with normal PKAc. An important insight has been that the subcellular anchoring of DNAJ-PKAc is less constrained than that of normal PKAc.
A major goal of the current study is to understand precisely how the altered anchoring of DNAJ-PKAc and its deregulated activity contribute to the cancerous transformation of liver cells. The team believes that such insight could point to novel ways to attack FLC with specific drugs or combination therapies.