Defining the function of Lgr6 stem cells in lung adenocarcinoma
For Translational Cell & Tissue Research we are looking for a student with interest and curiosity in basic molecular and cellular research. The candidate will have to perform cellular and molecular techniques and learn some of the state-of-the-art methodology to genetically manipulate cells and tissues. This position will be paid by a grant for up to three years. During this period the candidate is supposed to obtain results and data to be published in international scientific publications, attend and present the work in scientific meetings (national and/or international) and write and defend a thesis in order to obtain the PhD degree. The group will provide the material, facilities and reagents necessary to perform the required experiments and validations. Translational Cell & Tissue Research is a group that combines medical and basic researchers. The goal of the unit is to study and understand cellular functionalities in different tissues and apply this knowledge to the treatment, prevention and regeneration of diverse pathologies. Knowledge and expertise in the use of different methodologies is provided and the collaboration between different laboratories to improve the quality of the research is part of the unit interest.
Investigation in lung cancer has been increased in thelast decades, as this disease has become one of the most deadly diseases in thedeveloped countries. However, it is still a poorly understood cancer andtherapies used have only marginally improved the survival rates. Cancer relapseafter drug treatment with more virulent and drug resistant tumors is the commoncause of failure to reduce survival. Understanding of the cellular andmolecular components of that behaviour is a main interest in current lungcancer research. Our lab has previously described Lgr6 as a lung stem cellmarker (1). In addition, we have observed the enrichment in Lgr6+ cells duringlung adenocarcinoma progression (2). Lgr6+ cells harbor stem cell properties(self-renewal and differentiation), and higher tumorigenic potential. Themechanism of selection includes defective repression of the miR-17-92 cluster.High levels of the miR-19 member target and reduced p38a protein levelsproviding a specific survival signal for Lgr6+ cells, mediated by increasedWnt/b-Catenin activity. This targeting of a molecular pathway in a definedcellular type may help to better detection and treatment of more malignantadenocarcinomas.We are now interested in a functional andmolecular characterization of these Lgr6+ tumoral cells. Tumorigenicity,invasion and metastatic potential will be addressed and assessed in vitro andin vivo. Multiple in vitro techniques will be used such as soft agar growth,boyden chambers, ex-vivo tumor growth and stem cell differentiation (usingmouse and human lung explants), and genetic expression profile of Lgr6+ cellsfrom human lung tumors at different stages of cancer development. We have broadexperience in the use of all those techniques and the culture of multipleprimary lung and tumor cells (1, 3, 4). The outcome of these investigationswill produce pivotal information about the process of cellular malignizationduring lung adenocarcinoma progression with high potential to translate in tothe clinic and applications for future testing and assessment of therapeuticdrugs to treat lung cancer.
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