Impact of sympathetic autonomic innervation of the tumor microenvironment on the progression of human hepatocellular carcinoma.
4 Apr 2024
Job Information
- Organisation/Company
Université de Rennes- Department
NUTRITION, METABOLISME et CANCER- Research Field
Biological sciences » Biological engineering- Researcher Profile
Leading Researcher (R4)- Country
France- Application Deadline
18 Jun 2024 - 00:00 (Europe/Paris)- Type of Contract
Temporary- Job Status
Full-time- Hours Per Week
35- Offer Starting Date
1 Oct 2024- Is the job funded through the EU Research Framework Programme?
Not funded by an EU programme- Is the Job related to staff position within a Research Infrastructure?
No
Offer Description
Hepatocellular carcinoma (HCC) is the second deadliest cancer worldwide. It has been classified by the French National Cancer Institute (INCa) as a poor-prognosis cancer, with a 5-year survival rate of less than 33%. The chronic fibroinflammatory liver disease background leads to increased innate immune reactivity and extracellular matrix remodeling.1 This microenvironment sets the stage for the emergence of cancer stem/progenitor cells.
HCCs are generally highly cellular tumors, with a soft consistency on macroscopic examination and little intratumor fibrosis. However, within certain HCCs, fibro-inflammatory foci may be distinguished on microscopic examination. These foci are composed of extracellular matrix, cancer-associated fibroblasts, immune cells and growth factors and have been called "Fibrous Nests."2-3 HCCs containing fibrous nests are enriched in cancer stem/progenitor cells, WNT/TGFB signals;2-3 and their proteomic signatures;4-5 indicate that they belong to the most aggressive class of HCCs, known as ECM/STEM.6-7
Intra-tumor fibrosis in HCCs may be linked to an immunosuppressive environment and to the presence of sympathetic nerve endings at the tumor invasion front. In this microenvironment, cancer-associated fibroblasts, neo-formed sympathetic nerve endings and the extracellular matrix could exert mechanical forces activating pro-tumor signals leading to the amplification of cancer stem/progenitor cell populations and tumor invasion.
Our project aims to assess the impact of intra-tumor fibrosis and its sympathetic innervation on HCC progression. The hallmarks of this three-year PhD project include prognostic evaluation of fibrosis and sympathetic innervation in 200 HCC cases (project approved by the INSERM Ethics Committee), analysis of the mechanical forces therein, affected signaling networks, and in vitro modeling of mechanical forces under defined adrenergic environments and extracellular matrix compositions.
This thesis project will provide crucial prognostic and mechanistic data on the role of intra-tumor fibrosis and sympathetic innervation in HCC progression, paving the way for targeted pharmacological approaches to control cellular phenotypes. The selected PhD candidate will evolve within a multidisciplinary research team, including anatomic pathologists, surgeons, cell and molecular biologists and specialists in bio-informatics.
References:
Requirements
- Research Field
- Biological sciences » Biological engineering
- Education Level
- Master Degree or equivalent
Skills/Qualifications
Master 2 training and/or Engineering School in: Molecular and Cellular Biology with a focus on any or some of the following disciplines: Human Health, Bioinformatics, Biostatistics, Histology, Histopathology, Oncology. Bench experience in cell culture, molecular biology techniques and histo-technology will be highly appreciated.
Doctors in Medicine, Pharmacy or Veterinary Medicine are also welcome.
Candidates are expected to be fluent in English (written and spoken). Basic notions of French will be highly appreciated because these will facilitate social interactions in the candidate’s personal and professional life.
Specific Requirements
This is an offer for individuals seeking to register as PhD Candidates at the University of Rennes, France. As such, they will commit to defend their PhD thesis at the end of the 3rd year of the contract.
- Languages
- ENGLISH
- Level
- Good
- Languages
- FRENCH
- Level
- Basic
- Research Field
- Biological sciences » Biology
Additional Information
Benefits
The selected PhD candidate will benefit from a 3-year Doctoral Contract from Rennes University.
The net salary is about 1900 euros per month, with 100 euros yearly increment.
Eligibility criteria
- Candidates should be available to take the position not later than December 2024.
- Required education and qualification as described in Skills/Qualifications.
- Bench experience level.
- English language skills (written and oral): fluency, vocabulary, reading comprehension of scientific texts (articles, protocols).
- Skills in oral presentation of scientific data.
- Academic background and recent academic scores.
- Interest in basic and translational research related to human oncology.
- Interest in molecular biology, histopathology, molecular pathology.
- Interest in developing bio-informatics skills.
Selection process
Applicants should address their CV and motivation letter to Dr Caroline Aninat and Dr Orlando Musso by e-mail. Applicants going through the first selection phase will be auditioned by Drs Aninat and Musso (either in the lab or remotely through videoconference).
The first interview will consist of an informal chat followed by a 15-minute presentation of their past education/experience using a visual support (eg., Power Point presentation or equivalent) and discussion for additional 15 minutes.
On a second interview, candidates may be provided with one or more scientific documents to analyze and comment using a visual support. The document(s) will be sent by e-mail sometime before the 2nd interview.
On the third, final interview, the selected candidate with be auditioned by a laboratory committee composed of a member of the Rennes University Doctoral School staff, as well as the laboratory director and deputy directors.
All auditions may be carried out either in the lab or remotely through videoconference.
Work Location(s)
- Number of offers available
- 1
- Company/Institute
- Institut Nutrition, Métabolismes et Cancer (NuMeCan), Univ Rennes, INSERM, INRAe
- Country
- France
- City
- RENNES
- Postal Code
- 35033
- Street
- 2 RUE HENRI LE GUILLOUX
- Geofield
Where to apply
[email protected]
Contact
- City
RENNES- Website
https://www.univ-rennes.fr/
https://numecan.fr/homepage/
https://www.inserm.fr/en/home/
https://pro.inserm.fr/- Street
RUE HENRI LE GUILLOUX- Postal Code
35033
[email protected]
[email protected]
STATUS: EXPIRED