Luxembourg Institute of Health (LIH) is the leading public research center in Luxembourg for basic, pre-clinical and clinical research in biomedicine and public health. Our clinically-oriented biomedical research activities in Oncology,Infection & Immunity and Population Health encompass the generation of knowledge on the pathogenesis, diagnosis and treatment of diseases with large impacts on public health and the epidemiological surveillance of these diseases.
With the mission to deliver scientific, economic and societal value for Luxembourg, LIH aims to translate knowledge into clinical applications impacting on healthcare systems while shaping personalized medicine.
Invadopodia are actin-rich membrane protrusions that facilitate tumor cell invasion through dense extracellular matrix (ECM) by recruiting transmembrane and secreted metalloproteinases (MMPs) able to catalyze ECM component degradation, and creating pores through which mesenchymal tumor cells can migrate. We recently identified CRP2 (cysteine- and glycine-rich protein 2) as a critical, cytoskeletal component of invadopodia (Hoffmann et al. 2016 Oncotarget 7: 13688-13705; Hoffmann et al. 2018 Scientific Reports 8: 10191). From a mechanistic standpoint, we found that CRP2 promotes invadopodia formation and elongation by stabilizing their actin core, which serves as a backbone of the structure. In addition, CRP2 shuttles to the nucleus where it drives expression of pro-metastatic genes, including several members of the matrix metalloproteinase (MMP) family involved in ECM remodeling and which are associated with cancer cell invasion and metastasis (Brown-Clay et al. in revision).
Interestingly, CRP2 is often strongly present in non-cancer cells, particularly cancer-associated fibroblasts (CAFs) in the surrounding microenvironment, suggesting an additional role for CRP2 in the stromal compartment. Based on our preliminary data we hypothesize that, in addition to increasing the (intrinsic) invasive capability of breast cancer cells, CRP2 also contributes to the CAF phenotype, and thereby facilitates ECM remodeling and breast cancer cell dissemination through a cancer cell extrinsic mechanism. This project aims to evaluate this hypothesis, elucidate the underlying molecular mechanism(s) and determine the prevalence and significance of stromal CRP2 in human breast cancer.
The Cytoskeleton and Cancer Progression (CCP) group belongs to the Department of Oncology, whose activities focus on the cellular and molecular mechanisms of tumor progression using a wide range of cutting edge technologies, including genomic, transcriptomic and proteomic analyses, and in vitro and in vivo imaging modalities as well as state-of-the art animal models for cancer research. The CCP group focuses on actin regulatory proteins and related signaling pathways driving tumor cell invasion and immune evasion (Al Absi et al. 2018 Cancer Research 78: 5631-5643), with the goal to identify new prognostic markers and therapeutic targets. We combine biochemistry, cell biology, reverse-genetics and advanced live-cell imaging approaches as well as mouse models of breast cancer metastasis.
Key Skills, Experience and Qualifications
- PhD in Biomedical Sciences. Prior experience in (breast) cancer research and/or in cytoskeleton-driven processes would be an advantage.
- Hands-on experience in experimental lab work using invasion/migration assays.
- Experience in cell imaging approaches.
- Experience in animal experimentation. FELASA or equivalent would be considered as an asset.
- Excellent planning and communication skills. Perseverance, originality, writing skills.
- Fluency in English is mandatory.
For more information please contact: Clément Thomas: firstname.lastname@example.org
Located in Luxembourg, LIH offers the opportunity to work in a dynamic, international and multilingual
environment that values personal respect and professional achievement based on the highest intellectual and ethical standards.
Applications including cover letter, CV, list of publications and name of two referees should be sent before 30 September 2019 through our website
www.lih.lu/jobs with the Ref: VD/PDFCI0719/CT/LECR