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Cell Proliferation

Jesus Gil

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Medical Research Council (MRC)
The ultimate goal of our group is to identify novel genes involved in cancer and analyze how they are related with the genetic networks regulating cell proliferation. Normal cells have a limited ability to proliferate. When primary cells reach this limit or upon the expression of some oncogenes, they cannot growth anymore, suffering an irreversible growth arrest termed senescence.||Specifically our laboratory works in understanding senescence as it is a tumour suppressor mechanism that hinders tumour progression but also since we can use it as a model system, as often the genes identified in this way have a role in cancer or other human diseases. We use normal cells (different human and mouse cells of epithelial and fibroblast origin) and perform genetic screenings to identify genes regulating their lifespan. We use cDNA, shRNA and microRNA retroviral or lentiviral libraries in our screenings. As we already mentioned, we are interesting in identifying new genes or genetic elements regulating senescence and possibly impacting in cancer. Current experiments have identified novel candidates which a role in senescence, and we are performing genetic and molecular biology-based experiments to understand how they relate to the core pathways controlling senescence and oncogenesis.||In the past, using genetic screenings, we identified the role of glycolytic enzymes in senescence and cancer and how the Polycomb group (PcG) gene CBX7 modulates cellular lifespan by repressing the transcription of the Ink4a/Arf locus and therefore interfering with the Rb and p53 pathways. An area of continuous interest in our laboratory is to further understand the mechanism of action of CBX7 and which is its function under physiological and pathological conditions. We are pursuing that goals through the characterization of CBX7-interacting proteins that we have identified in yeast-2-hybrid screenings and by tandem affinity purification (TAP) followed by Mass Spectroscopy (MS). We are characterizing three interesting candidates flagged through those approaches. ||On the other hand, we have developed appropriate models through our collaboration with Scott Lowe (CSHL, NY, USA) to understand the role of CBX7 in cancer and in normal and pathological circumstances.

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