Poste basé à Bordeaux
Description of the tasks
The incidence of common skin cancers, including basal cell carcinomas (BCCs), squamous cell carcinoma (SCC) and melanomas, continues to rise by 5 to 7% per year, mainly due to ultraviolet (UV) exposure and partly because of increased longevity in general population and immunosuppressive medication. On a yearly basis skin cancer incidence is higher than the combined incidence of breast, prostate, lung and colon cancers, with a huge economic impact. This data suggests an urgent necessity to improve the level of prevention and protection for skin cancers as well as developing new prognostic and diagnostic biomarkers of skin cancers. Cutaneous SCC (cSCC) typically manifests as a spectrum of progressively advanced malignancies, ranging from a precursor actinic keratosis (AK) to cSCC in situ, invasive cSCC and finally metastatic cSCC. We have recently showed that 1) specific metabolic modifications precede cSCC, 2) bioenergetic metabolism play a key role in photocarcinogenesis, and 3) dihydroorotate dehydrogenase (DHODH) inhibition is a promising target for chemoprevention of UVB-induced cSCCs. Our preliminary data using proteomic-based metabolic profiling reveals interpatient metabolic heterogeneity and defines three subgroups. In continuity, we plan to determine whether the metabolic and immune profile of skin at different stages of carcinogenesis can be used to develop specific clinically-oriented biomarkers. To this end, we will use the transgenic mouse models as well as tumor cell lines. Metabolic profiles will be determined by proteomic and metabolomics analysis as demonstrated in our recent publication (Cell reports, 2018; Oncogenesis 2019). Immune profiling will be done by transcriptomic and flow cytometry. The immune profiles will be determined by single cell RNA sequencing technology, which allows to characterize different cell subtypes within a tumor and therefore to determine the precise phenotypic structure of tumor.
1: Kaulanjan-Checkmodine P, Oucherif S, Prey S, Gontier E, Lacomme S, Loot M, Miljkovic-Licina M, Cario M, Léauté-Labrèze C, Taieb A, Moisan F, Rezvani HR. Is Infantile Hemangioma a Neuroendocrine Tumor? Int J Mol Sci. 2022 May 5;23(9):5140. doi: 10.3390/ijms23095140. PMID: 35563552; PMCID: PMC9104933.
2: Moisan F, Oucherif S, Kaulanjan-Checkmodine P, Prey S, Rousseau B, Bonneu M, Claverol S, Gontier E, Lacomme S, Dousset L, Couffinhal T, Toutain J, Loot M, Cario-André M, Jullié ML, Léauté-Labrèze C, Taieb A, Rezvani HR. Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade. Proc Natl Acad Sci U S A. 2021 Feb 16;118(7):e2018690118. doi: 10.1073/pnas.2018690118. PMID: 33558238; PMCID: PMC7896303.
3: Hosseini M, Dousset L, Michon P, Mahfouf W, Muzotte E, Bergeron V, Bortolotto D, Rossignol R, Moisan F, Taieb A, Bouzier-Sore AK, Rezvani HR. UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis. Oncogenesis. 2019 Sep 24;8(10):52. doi: 10.1038/s41389-019-0161-z. PMID: 31551419; PMCID: PMC6760220.
4: Mahfouf W, Hosseini M, Muzotte E, Serrano-Sanchez M, Dousset L, Moisan F, Rachidi W, Taieb A, Rudolf J, Rezvani HR. Loss of Epidermal HIF-1α Blocks UVB-Induced Tumorigenesis by Affecting DNA Repair Capacity and Oxidative Stress. J Invest Dermatol. 2019 Sep;139(9):2016-2028.e7. doi: 10.1016/j.jid.2019.01.035. Epub 2019 Mar 13.
5: Hosseini M, Dousset L, Mahfouf W, Serrano-Sanchez M, Redonnet-Vernhet I, Mesli S, Kasraian Z, Obre E, Bonneu M, Claverol S, Vlaski M, Ivanovic Z, Rachidi W, Douki T, Taieb A, Bouzier-Sore AK, Rossignol R, Rezvani HR. Energy Metabolism Rewiring Precedes UVB-Induced Primary Skin Tumor Formation. Cell Rep. 2018 Jun 19;23(12):3621-3634. doi: 10.1016/j.celrep.2018.05.060. PMID: 29925003.
Basic knowledge of molecular and cellular biology, biochemistry and immunology
– real interest for the work on animal models
– competence in histology and immunohistochemistry is desired
– The control of cell culture techniques and / or real-time PCR and / or flow cytometry will be appreciated.