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Mechanisms of mesothelioma resistance to chemotherapy.
Belgium (BeMSA) - Université de Liège, Liège
Laboratory of Tumours and Development Biology GIGA
Prof. Didier Cataldo
Prof. Didier Cataldo
Type of Research Project
- Basic science
What is the background of the project?
Resistance to chemotherapy is a key issue in mesothelioma management. In the field of cancer cell chemoresistance, recent mechanisms have been identified. The “long non-coding RNA” (lncRNA) that are non-coding transcripts longer than 200 nucleotides have recently been described to play a role in mechanisms of resistance to chemotherapeutic agents in the breast, gastric and lung cancers. Active A Disintegrin and Metalloprotease (ADAM) proteases also play a role in chemoresistance. Membrane-bound growth factors shedding by ADAM proteases is a mechanism of autocrine loops activation in human tumors (e.g., TGFalpha released by ADAM17). We developed strong preliminary data on the role of ADAM8 in chemoresistance of mesothelioma. Epithelial to mesenchymal transition (EMT) is also a chemoresistance mechanism in several cancers. We developed in the last years' different tools that will be useful for this project, including human mesothelioma samples, a mouse model of asbestos fibers-induced mesothelioma, primary mesothelioma cell lines, and cisplatin-resistant mesothelioma cell lines.
What is the aim of the project?
The main objective of this project is to use an innovative approach to describe new mechanisms of mesothelioma resistance to chemotherapy.
What techniques and methods are used?
This project is based on strong preliminary results; it is articulated in two axes: (1) We propose hypothesis-driven research based on our preliminary results assigning a role for ADAM8 in mesothelioma resistance to cisplatin. The main objective of this work package will be to define the mechanisms leading to ADAM8-induced resistance to cisplatin. (2) We will characterize and perform a high-throughput study of transcriptome on cisplatin-resistant cells recently generated in the lab. This study will include a thorough investigation of lncRNA expression and function Mouse models of cancer dissemination including biophotonic imaging techniques, histology, protein studies (ELISA (Enzyme-Linked ImmunoSorbent Assay), western blots), nucleic acid studies (RNA sequencing, RT-PCR (Reverse Transcription Polymerase Chain Reaction), quantitative PCR (Polymerase Chain Reaction)), Cell cultures and studies of cell behaviors (Wound healing assay, cell proliferation measurement, survival measurements, organoids).
What is the role of the student?
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
- The tasks of the student will be performed on his/her own
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
Students will have an active role in the research project receive theoretical and practical knowledge. This will allow them to develop a strong scientific background in the area of lung cancer. The student will assist the tutor and the technical assistant of the lab in performing the described project and at the end of the month, she/he will be able to perform some of the methods (Cell Culture, analysis of histology, analysis of samples) An active discussions/contributions by the applicant and current lab members will be expected. Therefore, high motivation and enthusiasm for science is a prerequisite to join our lab.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes, it will: -Preliminary readings. -Preliminary courses. A brief overview of the topic will be given when he/she arrives.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster - The student will prepare a presentation - The student will prepare a scientific report
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Minimal knowledge about biology and histology. Previous experience with lab work is, of course, an advantage but not mandatory.
Are there any legal limitations in the student’s involvement
Direct use of animal models is not authorized. Unless the student holds an international certificate allowing him/her to handle animals (e.g. FELASA certificate).
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system - Students in biomedical fields
- Sépult C; Bellefroid M; Rocks N; et al. ADAM10 mediates malignant pleural mesothelioma invasiveness. Oncogene. 2019;38(18):3521-3534. doi:10.1038/s41388-018-0669-2
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