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The University of Vermont Cancer Center
Characterizing enzyme inhibition of the DnaJPKAc chimeric protein derived from fibrolamellar hepatocellular carcinomas 2017 – 2019
Principal Investigator: Hibba tul Rehman, M.D., University of Vermont
Scientists have identified a unique fusion protein, DnaJ-PKAc, which causes this cancer. When overexpressed, this protein causes havoc in the downstream signaling pathways that are involved in cell growth and metabolism and is thought to be the key driver for cancer growth. Based on the 100% presence of the chimeric DnaJ-PKAc protein in FL-HCC patients, we are proposing a two pronged approach towards the regulation of the cancer cells. First, we will screen a previously developed peptide library to test the substrates against purified wild-type vs. the chimeric DnaJ-PKAc in vitro. Second, we propose to develop a library of inhibitory peptides that would preferentially inhibit DnaJ-PKAc. The studies suggested here should allow us to develop inhibitors that regulate the function of the chimeric enzyme without affecting the wild- type enzyme, thus selectively targeting cancer cells without affecting healthy tissue.