Timeframe: 2019 – 2021
Goal: Development of a novel human-derived liver progenitor cell line model of fibrolamellar carcinoma
Principal Investigator: Khashayar Vakili, MD, Surgical Director of Liver, Kidney, Intestine, and Multivisceral Transplant Programs, Assistant Professor of Surgery, Harvard Medical School
The study team’s lab previously engineered a kidney cell line (HEK-DP) which contains the DNAJB1-PRKACA fusion gene found in FLC tumors. This cell line demonstrates interesting similarities to FLC tumors and serves as a proof of concept for the development of additional cell lines. This effort applied apply the same strategy used to engineer the HEK-DP model to engineer normal human liver progenitor cells to express the DNAJB1-PRKACA fusion gene. These liver progenitor cells were to be grown as three-dimensional “organoid” cultures to better replicate in vivo conditions.
If successful, this novel model will facilitate understanding how the fusion protein reprograms normal liver progenitor cells to become cancerous. Understanding the precise mechanisms underlying the formation of FLC will provide insights to future therapeutic strategies.