JOIN THE CRCT

­­Junior Post-Doctoral Position

Equipe MICROPANC – Corinne Bousquet, CRCT)

Research Project / Missions / Scientific context

A postdoctoral research fellow position is available for 3-years at CRCT (Toulouse Cancer Research Center) in Corinne Bousquet’s Research group « Microenvironment & Therapeutic Resistance in Pancreatic Neoplasms. »
The project aims at understanding pancreatic cancer heterogeneity in spatial cell positioning, focusing on the interplay between cancer cells, cancer-associated fibroblasts and immune cells, to understand immune cell exclusion within sub-tumor microenvironment areas. Within an European Consortium (Belgium, Spain, Italy & France), the role of specific guidance cues that may organize cell attraction or repulsion will be explored. To do so, multiplex RNA and protein immunohistofluorescence on pancreatic cancer tissue shall be developed, as well as functional assays using 3D cell co-cultures.
Toulouse is a dynamic research area located in south of France that comprises many internationally recognized laboratories (fundamental cell biology, pharmacology, cancerology, immunology, metabolism, agronomy…) and gives access to a network of high-level skills research platforms in life sciences (GENOTOUL – Un ensemble de ressources au service de la R&D, e.g. imaging, cytometry, bioinformatics, genomics & transcriptomics, biostatistics ; Metatoul – Home (inrae.fr), e.g. metabolomics & fluxomics; Toulouse Proteomics Infrastructure | IPBS, e.g. proteomics) making possible almost all research projects.
The Toulouse Cancer Research Center, accredited by INSERM, CNRS and Toulouse University, is internationally recognized and offers a productive scientific environment centered on basic, transdisciplinary (bioinformatics, mathematics & physics in close link with the Toulouse Laboratoire d’analyse et d’architecture des systèmes | LAAS-CNRS and Laboratoire de Physique et Chimie des Nano-objets (insa-toulouse.fr)), and clinical research (in close link with the IUCT Oncopole – Institut Universitaire du Cancer de Toulouse – Accueil (iuct-oncopole.fr)), to understand and treat cancers. CRCT brings together a total of >250 Researchers, MDs, University Professors, Technicians, Students and Post-docs of many nationalities. CRCT offers on-site state-of-the-art technological platforms with personalized project support, including single cell RNAseq (Le pôle technologique DU CRCT – Centre de Recherches en Cancérologie de Toulouse (crct-inserm.fr)).

Main missions :

• Multiplex imaging (RNAs & Proteins) and image analyses on pancreatic cancer tissues
• Set up of 3D co-cultures of patient-derived cancer-associated fibroblasts with cancer cells and immune cells
• Functional characterization of selected guidance cues using molecularly engineered 2D and 3D patient-derived cell models, and in vivo murine models of pancreatic cancer (orthotopically grafted with cancer cells).
• Experimental design & organization, Statistical analysis, Result interpretation & reporting (oral in english during Labmeetings; written for grant reporting & application, and manuscript preparation)
• Involvement in the tutoring of 1 to 2 Master/ PhD Students
• Strong interaction with other Lab members (help with experiment design, interpretation,…)

Contract :

• Type : CDD
• Length  : 36 months
• Salary : 2.856,02€ gross monthly depending on experience post-PhD.Salary will follow INSERM guidelines commensurate with training and experience
• Starting date Position  : starting in April 1rst, 2023, the latest

To Apply :

Please send a motivation letter explaining your interest in this job advertisement, CV and the names of three references to: corinne.bousquet@inserm.fr

Consulter le profil de poste complet(en anglais)

­­Post-doc Position in 2023: Targeting pre-leukemic stem cells in B-cell acute lymphoblastic leukemia

(Bastien GERBY, Cancer Research Center of Toulouse, France)

General problematic: The cell of origin of B-ALL

B-cell acute lymphoblastic leukemia (B-ALL) is a multi-step disease characterized by the acquisition of a first oncogenic event such as ETV6::RUNX1, BCR::ABL1 or TCF3::PBX1 fusion genes or specific PAX5 alterations (such as PAX5::ELN or P80R point mutation). Genome-wide analyses have been used to draw the genomic landscape and the gene expression profile of B-ALL patients leading to patient stratification and the discovery of new therapeutic opportunities. However, although chemotherapies are efficient at reducing the tumor load by targeting proliferating and metabolically active leukemic cells, the disease relapse, especially in adult B-ALL, points to the presence of resistant cells that escape treatment. Thus, the biological properties of the cell-of-origin of leukemia, including oncogene-induced reprogramming, cell plasticity, sustained self-renewal activity, cell-quiescence and drug-resistance, can affect the treatment and should be considered in the search for new targeted therapies (Fregona V et al., Cancers (Basel) Review, 2021).

Research Context: A unique murine model of B-ALL

In this context, our research focuses on the characterization and the targeting of pre-leukemic stem cells (pre-LSCs) in B-ALL. We develop cellular and animal models aiming to understand how a primary oncogene in B-ALL such as a chromosomal translocation, reprograms normal B-cells to pre-LSCs as demonstrated in our 2018 PNAS paper. Indeed, we generated the PAX5::ELN transgenic mouse model that recapitulates the multi-step process of B-ALL and that represents a prime tool to explore the pre-leukemic phase of the disease before the overt transformation (Jamrog L et al., PNAS, 2018). Our recent work indicates that pre-LSCs: (i) are restricted in the cell-cycle, (ii) are devoid of secondary mutations, (iii) are blocked in the B-cell differentiation, (iv) are resistant to chemotherapeutic agents, (v) up-regulate a stem cell-like molecular programs and (vi) sustain the leukemia initiation and transformation. Thus, our work indicates that PAX5::ELN reprograms stem cell-like properties in a subset of B-cell progenitors and converts them into quiescent pre-LSCs (Fregona V et al., submitted).

Proposed project: Targeting leukemia initiating activity

We recently designed a robust protocol for the screening of compounds targeting primary pre-LSC-enriched population. We screened a bank of 1040 natural and synthetic compounds and identified drug candidates that affect their viability. Using further investigations (counter screens on quiescent cells, dose-responses, synthetic lethality assays, RNA-sequencing, transplantation assays), the post-doc candidate will have in charge to identify the most relevant compound that affects the cell-quiescence/resistance, the self-renewal potential and the gene expression profile of PAX5-ELN pre-LSCs. In addition, the candidate will define whether targeting pre-LSC biological properties is relevant in other B-ALL models available in the lab (PAX5-P80R and TCF3::PBX1 mouse models or human B-ALL patient-derived-xenografts (PDXs)).

Candidate profile and application

We are seeking a dynamic and proactive post doc. The candidate should have good experience in mouse models, flow cytometry, as well as in culture of primary cells. Skills in hematopoiesis and in bioinformatics would be very welcome. With our strong help and support, the selected candidate will have to apply in 2023 for a Postdoctoral Fellowship from different institutions (Fondation ARC, Fondation pour la Recherche Médicale, Fondation de France,…). The applicant is invited to send a CV with list of publications, research experiences and referees to Bastien Gerby (bastien.gerby@inserm.fr).

Situation & scientific environment

Our team “Impact of genetic alterations on leukemia development” led by Pr. Eric Delabesse is located at the Cancer Research Center of Toulouse (CRCT, UMR1037, CNRS UMR5071). The team is composed of 16 people including two PU-PH, three researchers, four engineers, two technicians and five students at the MSc and PhD levels. The laboratory promotes multidisciplinary approaches allowing an efficient investigation and deeper understanding of normal and aberrant hematopoiesis. Combined with clinical studies and genetic profiling of leukemia patients, the development in our team of cellular and animal models aims to define and target the biological mechanisms by which genetic alterations lead to leukemia development. The projects are supported by grants from INCa, ANR, ARC Foundation, Ligue Contre le Cancer and from the associations “Laurette Fugain”, “111 des arts”, “Cassandra” and “Constance la petite guerrière astronaute”.

As a post-doc, you will have a full access to facilities available in the CRCT (https://www.crct-inserm.fr/en/the-technology-cluster-of-the-crct/) including flow cytometry/cell sorting, bioinformatics, vectorology and genomics platforms.

Webpages of the team:

https://www.crct-inserm.fr/en/characterization-and-targeting-of-pre-leukemic-stem-cells-from-b-acute-lymphoblastic-leukemia/
https://www.crct-inserm.fr/en/igaald_en/
https://www.crct-inserm.fr/en/axis-1-oncogenic-pathways-in-cancer-from-modelization-towards-targeted-therapy/ 

Contacts:

Project leader: Dr. Bastien Gerby: bastien.gerby@inserm.fr Team leader: Pr. Eric Delabesse: delabesse.e@chu-toulouse.fr

Selected references:

• Fregona V et al. Cell quiescence and reprogramming are distinctive features of pre-leukemic stem cells in B-cell acute lymphoblastic leukemia. Submitted.
• Fregona V et al. Oncogene-Induced Reprogramming in Acute Lymphoblastic Leukemia: Towards Targeted Therapy of Leukemia Initiating Cells. Cancers (Basel) Review, 2021 Nov 2, 13(21):5511.
• Duployez N et al. Germline PAX5 mutation predisposes to familial B acute lymphoblastic leukemia. Blood, 2021 Mar 11;137(10):1424-1428.
• Jamrog L et al. PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice. Proc Natl Acad Sci USA. 2018 Oct 9;115(41):10357-62.
• Cresson C et al. PAX5A and PAX5B isoforms are both efficient to drive B-cell differentiation. Oncotarget. 2018 Aug 28;9(67):32841-54.
• Gerby B et al. High-throughput screening in niche-based assay identifies compounds to target pre-leukemic stem cells. J Clin Invest. 2016 Dec 1;126(12):4569-84.
• Gerby B et al. The SCL, LMO1 and Notch1 oncogenes reprogram T-lymphocyte progenitors into self-renewing cells. PloS Genetics. 2014 Dec 18;10(12).

Postdoctoral position (M/F; 1 yr, renewal 3 yrs)​

PROJECT

IRONAML53 – Uncovering and targeting metabolic vulnerabilities of acute myeloid leukemia harboring TP53 mutations, promoting Darwinian advantages in leukemic evolution and drug resistance

The postdoctoral fellow will be implicated in a highly collaborative project between the CRCT (JE Sarry,Toulouse), METATOUL (JC Portais, Toulouse), IRCM (L Le Cam, Montpellier) and Cochin (C Peysonneaux, Paris). The postdoctoral fellow will establish unique PDX models (well handled by the
CRCT) and novel GEMMs and will study cellular and metabolic mapping of TP53 mutant leukemic blasts and their microenvironment in those models. He/she will be devoted to unravel the role of host iron in the development of selective advantage and chemoresistance of distinct TP53 clones. Her/his work will be done in close collaboration with PhD students and engineers working on the multidisicplianry project. General responsibilities include design, implement and interpret experiments, both independently and in collaboration, and communicate research and findings in a clear and concise
manner. The postdoctoral fellow will present the progress of the project during bi-monthly meetings between the different teams, as well as during national and international conferences.

EMPLOYMENT

Starting beginning of 2023, the job position is funded by an INCA-HRHG grant.
The application should be written in English and include:
1. Letter of motivation with a short description of the applicant’s previous research and why
the applicant considers her/himself a good match for the position (1-2 pages).
2. Curriculum vitae, including a description of relevant skills and experiences, as well as a full
publication list.
3. Names, e-mail addresses and telephone numbers to 2-3 references.

CONTACT

Application should be sent to Jean-Emmanuel Sarry (jean-emmanuel.sarry@inserm.fr).

More information >>>

Deciphering the complexity of aggressive breast cancer to improve survival

The Cancer Research Center of Toulouse (CRCT, Inserm / CNRS / University Toulouse III Paul Sabatier ), together with the Fondation Toulouse Cancer Santé and the Institut Claudius Regaud are launching a call for projects to recruit a research team working in the field of Triple Negative Breast Cancer (TNBC).

Triple Negative Breast Cancer (TNBC) is a highly heterogeneous and clinically aggressive neoplasm that accounts for 15-20% of breast cancers with the highest mortality rate of all breast cancer subtypes.

TNBC is defined by a poorly differentiated state, lack of expression of the estrogen receptor (ER) or progesterone receptor (PR), and without overexpression/amplification of human HER2. Unlike hormone receptor-positive breast cancer, which is usually treated with hormonotherapy, or HER2-positive breast cancer, which can be treated with therapeutic antibodies (e.g. trastuzumab), TNBC management do not benefit so far from effective targeted therapy, and conventional chemotherapy remains the standard of care for patients with limited clinical impact. In addition, the molecular biology of this cancer type is still poorly understood. Therefore, a better understanding of TNBC oncogenesis and the identification of novel actionable targets could greatly benefit to patients with this disease.

The objective of this Chair is to better understand the genetics, biology and microenvironment of TNBC, based on innovative technologies such as single cell molecular analysis, as a source for novel targets and therapeutic strategies.

This Chair is aimed at world-class researchers. The laureate will receive funding equivalent to an ERC Starting Grant of €1.5 million for a period of 5 years. The terms of the funding will be negotiated with the winner.

This chair complies with the CRCT’s scientific priorities and will benefit from the support of IUCT-Oncopole’s clinical and bioclinical teams who are currently investigating the genomic landscape and the characteristics of metastatic TNBC. The successful applicant will conduct world-class research using state-of-the art technological platforms, shared between the CRCT and the IUCT-Oncopole, for the molecular exploration of patient tissues.

Applications must include :

• A non-confidential summary of the project for the general public (maximum 1 page, Calibri 10 font)
• The complete scientific project, including the scientific objectives of the project, the methodology and techniques, as well as the expected results (5 pages maximum excluding figures, Calibri 10 font).
• The complete CV of the applicant.
• The complete list of the applicant’s publications.
• A proposed budget.

The evaluation of the projects will be done on site by an international external jury in spring 2023, with an expected start in autumn 2023. The exact timetable will be communicated to applicants at a later date.

Applications should be sent before 31 march 2023 to sebastien.guibert@inserm.fr