Background. Chronic Lymphocytic Leukemia (CLL) represents the most frequent leukemia in adults. Despite recent advances in treatments, CLL remains a deadly incurable disease. This cancer is characterized by an accumulation of abnormal, apoptosis-resistant B lymphocytes in the blood and lymphoid organs of the patients. CLL progression is highly dependent on complex interactions between tumour cells and their microenvironment. Indeed, CLL cells can modify stromal cells and immune cells, among others through the expression of chemo-attractant cytokines, i.e. chemokines to promote their survival and to escape the immune surveillance.
Objectives. Our team focuses on the mechanisms leading to leukemia progression, in particular the influence of exosomes, chemokines and atypical chemokine receptors on CLL cells as well as on stromal cells and immune cells located in their microenvironment, with the goal to identify novel regulatory pathways and new therapeutic targets.
Training and research environment. The candidate will be integrated in dynamic and multinational teams. The Department of Cancer Research and Department of Infection and Immunity whose research activities focus on the cellular and molecular mechanisms of tumour progression and inflammatory diseases using a wide range of cutting edge technologies, including genomic, transcriptomic and proteomic analyses, as well as in vitro and in vivo imaging modalities using state-of-the-art animal models for cancer and immunology research. PhD student will be in charge of a TELEVIE funded project that aims to explore the complex role of exosomes in the regulation of chemokine levels in the tumour microenvironment. The candidate will be co-supervised by Dr A. Chevigné, Dr J. Paggetti and Dr M. Szpakowska and will be registered at the University of Luxembourg.
Recent related references (open access):
- Paggetti J, et al. Exosomes released by chronic lymphocytic leukemia cells induce cancer-associated fibroblast formation. Blood 126(9):1106-17.
- Wierz M, et al. Dual PD1/LAG3 immune checkpoint blockade limits tumor development in a murine model of chronic lymphocytic leukemia. Blood 131(14):1617-1621.
- Meyrath M., Szpakowska M et al. The atypical chemokine receptor ACKR3/CXCR7 is a broad-spectrum scavenger for opioid peptides. Nat Commun. 2020 Jun 19;11(1):3033.
- Sjöberg et al. The diverse and complex roles of atypical chemokine receptors in cancer: From molecular biology to clinical relevance and therapy E, Adv Cancer Res. 2020;145:99-138
Key Skills, Experience and Qualifications
- Master’s degree in Biomedical Sciences or Immunology. Prior experience in cancer research would be an advantage but is not mandatory.
- Experience in cell culture, PCR, Western-Blot, imaging and flow-cytometry techniques.
- Mouse experimentation practice and FELASA diploma (or equivalent) would be considered as an asset.
- Excellent time management, rigour, perseverance, scientific creativity and originality, writing skills, sense of priority and ability to work with others.
- Fluency in English is mandatory.
Researchers are supported by easy access to scientific expertise, well-equipped facilities, an active seminar program as well as the possibility for close collaborations with universities and other research institutes
The applicants should submit before 28th February, 2022 a letter detailing their motivation and a curriculum vitae via our website (www.lih.lu/jobs ) with the ref. : VD/PHD0122/ACJP/TSI DII INF2
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