Elucidation of nuclear-mitochondrial signaling by DNAJ-PKAc to define targeted vulnerabilities in FLC

Timeframe: 2022 – 2025 Goals: Identifying how the DNAJ-PKAc/SIK/p300 program controls mitochondrial function and define how these abnormal mitochondria affect the metabolism of FLC cells Principal Investigator: Nabeel M. Bardeesy, PhD Study overview: Signals that control the growth and metabolism of cells often are relayed through a series of reactions in which proteins are sequentially …

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Targeting DNAJB1-PRKACA driven signaling dependencies in FLC

Timeframe: 2019 – 2022 Goals: Investigate the potential of AURKA inhibitors for FLC treatment Principal Investigators: John Gordan, MD, PhD (UCSF) and Nabeel Bardeesy, PhD (MGH) Study overview: Even though the DNAJB1-PRKACA gene fusion is sufficient to trigger fibrolamellar liver cancer (FLC), no treatments directed at this target are clinically available. Most FLC patients receive …

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Fibrolamellar carcinoma model development and analysis

Timeframe: 2020 – 2022 Goal: Model development Principal Investigator: Nabeel Bardeesy, PhD Study overview: While multiple FLC models have recently been developed, additional model development remains a priority for the FLC community. This effort aimed to develop multiple different FLC models as resources for the FLC research fibrolamellar cancer research community, collaborating with the Fibrolamellar …

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Flipping the switch on PKA: synthetic lethal approaches to block PKA-driven tumor growth in fibrolamellar liver cancer

Timeframe: 2016 – 2019 Goal: Understand growth mechanisms and identify potential therapeutic targets Principal Investigators: John Gordan, MD, PhD (UCSF) and Nabeel Bardeesy, PhD (Mass General Hospital) Study overview: The discovery of a genetic change in the protein kinase A (PKA) gene in nearly all cases of fibrolamellar liver cancer (FLC) creates hope that targeted …

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