Novel synergistic combination therapy in fibrolamellar carcinoma

Timeframe: 2022 – 2023 Goal: Knock-out gene targets in a mouse model of FLC to identify potentially effective drug combinations for patients with advanced FLC Principal Investigator: Sean Ronnekleiv-Kelly, MD Study overview: This study will apply an innovative gene-editing based technology (genome-wide CRISPR knockout screen) on a mouse cellular model to screen all possible cancer …

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Characterization of mitochondria alterations and their functional consequences in fibrolamellar carcinoma (FLC) and FLC-like BAP1 hepatocellular carcinoma

Timeframe: 2022 – 2024 Goal: Identify functional role of mitochondrial alterations in FLC and FLC-Like BAP1 HCC Principal Investigator: Jessica Zucman-Rossi, MD, PhD Study overview: Recently, important research studies have reported specific genomic abnormalities of tumor subtypes. One of these, representing the fusion between DNAJB1 and PRKACA genes, has been described to be typical of …

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Multicenter consortium to define the single-cell activity landscape of fibrolamellar carcinoma.

Timeframe: 2022 – 2024 Goals: Advance immunotherapy for FLC by defining promising immunological targets that can be translated into effective cell-based immunotherapies Principal Investigators: Praveen Sethupathy, PhD (Cornell University); Mark Yarchoan, MD (Johns Hopkins University); Paul G. Thomas, PhD (St. Jude Children’s Research Hospital) Study overview: Like tumors of other cancer types, the microenvironment of …

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Clinical trial protocol development

Timeframe: 2022 – 2024 Goals: Accelerate development of potential clinical trial Principal Investigator: Mark Yarchoan, MD Study overview: This grant to Dr. Yarchoan is meant to support the development of a protocol for a potential clinical trial. In 2020, the Johns Hopkins team began a phase I clinical trial of an experimental vaccine containing a …

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Defining the potential of DNAJB1-PRKACA fusion-specific T cells across human populations

Timeframe: 2022 – 2024 Goal: Defining the most promising immunological targets that can be translated into effective cell-based immunotherapies Principal Investigators: Paul G. Thomas, PhD Study overview: New immunotherapeutic approaches have produced spectacular outcomes for a small subset of tumors, including certain melanomas, lung cancers, and leukemias, but these dramatic cures have not been broadly …

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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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Development of a human-derived liver progenitor cell line with DNAJB1-PRKACA fusion gene and characterization of mitochondrial dynamics in fibrolamellar carcinoma

Timeframe: 2022 – 2023 Goal: Development of a novel human-derived liver progenitor cell line model of fibrolamellar carcinoma Principal Investigator: Khashayar Vakili, MD Study overview: Currently, very few cell-line models of FLC exist, so the development of additional cellular models is critical for the identification and testing of new therapies. Therefore, one of the aims …

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