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Reference : UMR7178-REGSOM-081
Workplace : STRASBOURG
Date of publication : Friday, June 4, 2021
Scientific Responsible name : DETAPPE Alexandre
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2021
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
Hypoxia is the hallmark of many solid tumor malignancies, supporting carcinogenesis as well as resistance to radiation and chemotherapy. Low oxygen levels within tumors result in hemodynamic changes that limit the transport of chemotherapeutics and that mitigate the efficacy of radiation therapy.
To date, significant efforts have been devoted to overcome the localized regions of tumor hypoxia, prompting the use of radiosensitizers, hypoxic cytotoxins, exogenous red blood cell transfusions, hyperbaric oxygen gas (O2), systemic erythropoietin, and nanoscale hemoglobin-based oxygen carriers that accumulate in the perivascular spaces of tumors by the enhanced permeability and retention (EPR-) effect. None of these approaches, however, have led to reliable successful results. Based on the understanding that aberrant blood vessel formation is one of seven underlying factors contributing to hypoxia, alternative therapeutic strategies have emerged that target the vascular biology of tumors. Whereas anti-angiogenesis inhibitors and nitric oxide (NO) donors promote vascular normalization, vascular disrupting agents (VDAs) have direct endothelial cell effects that inhibit tumor blood flow. As with most VDAs, they affect larger blood vessels and can cause alterations in systemic blood pressure. Depending on the molecule and its class, VDAs have disparate effects on the vascular beds of normal tissues: they may lead to diminished mentation, visual, GI, and urinary disturbances, cytopenias, and myocardial ischemia, amongst other adverse effects. In part because of these dose-limiting toxicities, the clinical efficacies of conventional vascular targeting agents are modest, irrespective of the choice of the tested agent, its dosing schedule, or whether it is administered as part of a combination regimen.
The doctoral student will work within the group of Alexandre Detappe at Institut de Cancérologie Strasbourg Europe and IPHC, in collaboration with the group of Loic Charbonnière at IPHC.
With about 2 postdoctoral fellows, 2 PhD students, 1 laboratory technician, multiple master 2 students, and 4 physicians, the laboratory develops novel drug delivery systems, antibody drug conjugates, immuno-nanotherapies with the ultimate goal to translate these findings to the clinic through the Institut de Cancérologie Strasbourg Europe. The laboratory is collaborating with various groups at the national level and with international laboratories (Dana-Farber, ETH Zurich, Technical University of Denmark).
The PhD student will benefit from a dynamic environment with various backgrounds, allowing a fast-pace research.
Constraints and risks
The future student will work daily with scientific English and within international collaborations.Strong team-work ability and motivation to visit foreign laboratories are strongly welcome.
Desired degree: Master or engineer specializing in nanomedicine, molecular biology, or biochemistry.
Experience in cell culture of cancerous lines (myeloma and / or breast), as well as experience with basic cell biology techniques would be a plus. This includes flow cytometry, western blot, cell isolation in human samples, RTqPCR.
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