Project description:cdipt is an essential gene in the synthesis of phosphatidylinositol (PtdIns) in the zebrafish, Danio rerio. The zebrafish mutant cdipt^hi559Tg (ZL782) carries a retroviral insertion which inactivates cdipt. Homozygous mutants exhibit hepatocellular endoplasmic reticulum (ER) stress and non-alcoholic fatty liver disease (NAFLD) pathologies at 5 days post fertilization (dpf). This study reveals a novel link between PtdIns, ER stress, and steatosis. We compared whole animal gene expression profiles of hi559 mutant larvae with phenotypically wild type larvae from a heterozygote incross in triplicate.
Project description:cdipt is an essential gene in the synthesis of phosphatidylinositol (PtdIns) in the zebrafish, Danio rerio. The zebrafish mutant cdipt^hi559Tg (ZL782) carries a retroviral insertion which inactivates cdipt. Homozygous mutants exhibit hepatocellular endoplasmic reticulum (ER) stress and non-alcoholic fatty liver disease (NAFLD) pathologies at 5 days post fertilization (dpf). This study reveals a novel link between PtdIns, ER stress, and steatosis.
Project description:Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, but outcomes for high-risk patients remain dismal, underscoring the critical need for novel therapeutic strategies. Our study demonstrates that RMS exhibits elevated de novo cholesterol biosynthesis. Silencing key cholesterol biosynthesis genes, such as DHCR7, disrupts cell cycle progression by inducing G2/M phase arrest. Additionally, inhibiting this pathway triggers endoplasmic reticulum (ER) stress, activates the unfolded protein response (UPR), and leads to apoptosis. These findings emphasize the essential role of de novo cholesterol synthesis in RMS and highlight a novel therapeutic strategy that targets this metabolic pathway to suppress tumor growth and promote apoptosis.
