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Trainee Spotlight: Linara Gabitova

  • Linara Gabitova
    Linara Gabitova
    Graduate Student
    Dr. Igor Astsaturov’s Lab
    Fox Chase Cancer Center
    [email protected]

     

     

     

     

    Biography

    I started studying biology in 5th grade, when I took advanced biology and chemistry courses at a school in Izhevsk, Russia. It was a great time for me as every biology lesson was full of wonderful adventures like listening to bird voices, growing plants from little seeds, exploring the cellular structure of thin layers of onion skin under the microscope! My love of science grew during the subsequent years at school, culminating in my application to the Biology Department at Kazan Federal University in Russia. During my second year of university, I became interested in cancer research. I joined a molecular pharmacology lab that was developing new polymer-based drug delivery systems for anti-cancer drugs. After graduating, I wanted to continue my education and explore research further.  I enrolled in a PhD program through Kazan Federal University and Fox Chase Cancer Center and ended up joining Dr. Igor Astsaturov’s lab.  Currently I study the regulation of cholesterol homeostasis as an important target for cancer treatment. My career goals are to finish my PhD and continue my research in identifying new therapeutic targets for successful cancer treatment.     

    Research Overview

    Cholesterol is a major component of lipid rafts; the membrane structures important for the proper receptor anchoring and cell signaling. It is known that transformed cells require elevated levels of cholesterol to support their rapid growth. This observation suggests that the targeting of cholesterol homeostasis will have a negative effect on tumor cell proliferation. In this study we investigated two enzymes of cholesterol biosynthesis pathway – NSDHL (NADPH-dependent steroid dehydrogenase-like) and SC4MOL (sterol C4-methyl oxydase-like), which catalyze the oxidative decarboxylation of the C4 methyl groups from meiosis activating sterols (MAS). Our prior studies showed that NSDHL and SCMOL deficiency caused accumulation of these metabolites in cells and also led to an inhibition of cell growth and proliferation. In our current paper, we reveal that accumulation of MAS upon NSDHL and SC4MOL deficiency activates the nuclear receptor Liver X receptor (LXR) and its transcriptional targets. This activation leads to decreased cholesterol uptake and increases the efflux of cholesterol through the ABCA1 transporter. This change causes a metabolic trap for cancer cells, depriving them of cholesterol and inhibiting their growth. Our data support the idea that sterol metabolites bridge proliferative and metabolic signaling pathways in normal and malignant cells.

    Featured Publication

    Endogenous Sterol Metabolites Regulate Growth of EGFR/KRAS-Dependent Tumors via LXR

    Linara Gabitova, Diana Restifo, Andrey Gorin, Kunal Manocha, Elizabeth Handorf, Dong-Hua Yang, Kathy Q. Cai, Andres J. Klein-Szanto, David Cunningham, Lisa E. Kratz, Gail E. Herman, Erica A. Golemis, Igor Astsaturov. Cell Reports, Volume 12, Issue 11, 22 September 2015, Pages 1927–1938

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