UMR-S 935 Inserm/University Paris Sud
Models of Malignant and Therapeutic Stem Cells
Director: Pr. Annelise Bennaceur
Unit 935 gathers researchers from three previously independent Inserm/UPS units with the goal of generating synergistic interactions in the field of malignant and therapeutic stem cells. In this configuration, Unit 935 associates a team with an expertise in adult and embryonic stem cell biology with two teams working on membrane compartmentalization and chronobiology/chronotherapy. This association should open new areas of research regarding tissue development and differentiation and promote technology transfer. These teams are in close relationship with a 4th team which coordinates a national technology transfer network INGESTEM dedicated to reprogramming strategies of adult cells into pluripotent stem cells (iPS).
Team 1 Leukemia, Cancer and Induced Pluripotency
Team leader : Pr. Ali Turhan (PU-PH University Paris Sud 11)
The field of stem cells has progressed in a spectacular way, both in Hemato-Oncology and in regenerative medicine. These progresses have been substantiated not only by seminal discoveries such as induced pluripotent stem cells (iPSC) but also by the identification of novel genotypic and phenotypic markers on normal and malignant stem cells and the elucidation of the novel intrinsic and extrinsic signaling pathways leading to their self-renewal, quiescence and long-term dormancy. This team concentrates its efforts on the use of novel stem cell models for the identification of stem cell-specific targets in malignant stem cells and on the generation of novel regenerative medicine strategies based on pluripotent and adult stem cell models. Some parts of the projects are basic science whereas other parts aim at translational research.
Project 1 : Chronic myeloid leukemia (CML) stem cells
Project 2 : Modelling cancer stem cells using iPSC - Models of BRCA1-positive hereditary cancer
Project 3 : Regenerative medicine applications using iPSC
Team 2 Membrane compartmentalization by tetraspanins and cell differentiation
Team leader : Dr. Eric Rubinstein (DR Inserm)
The aim is to deepen the understanding of the function of tetraspanins, their physiological role and their involvement in diseases, but also to use them as an original approach to better characterize certain aspects of cell differentiation and cancer progression. Four main projects are developed.
Project 1 : Regulation of Notch signaling by TspanC8 tetraspanin (Eric Rubinstein)
Project 2 : Deciphering the mechanisms of muscle cell fusion via the study of tetraspanins. Physiopathological implications (Stéphanie Charrin)
Project 3 : Targeting Tspan8 in colon cancer and melanoma (Claude Boucheix)
Project 4 : Study of the mechanisms underlying gamete fusion (Claude Boucheix, Eric Rubinstein)
Team-3 Chronotherapy of Liver Cancers and Optimization of Liver Function
Team leader : Pr. René Adam (PU-PH University Paris Sud 11)
The overall team project aims at improving the survival of patients with primary or secondary liver cancer through coordinated research on circadian clocks and optimization of liver function recovery after hepatic surgery or transplantation. The research program of this multidisciplinary team relies on its scientific and medical achievements regarding both the relevance of the Circadian Timing System for cancer processes and their treatments, and the successful integration of the new experimental, technical and clinical cancer chronotherapy research results within innovative medico-surgical strategies. The latter translational aspect has mostly aimed at the improvement of outcomes of patients with metastatic colorectal or pancreatic cancer with focus on the implementation of a patient-centered health care system fully integrating circadian rhythm concepts and technologies within the familial and social environment of the patients (Domomedicine).
Project 1 : Cancer Chronoprevention
Project 2 : Personalized Cancer Chronotherapy
Project 3 : Joint optimization of clinical tolerability and efficacy of cancer chronotherapy through personalized chronomodulated drug delivery: combining Domomedicine and Systems Medicine approaches
Project 4 : Optimization of liver function recovery after hepatic resection or transplantation
Team 4 R&D - ESTeam
Team leader : Pr. Annelise Bennaceur (PU-PH University Paris Sud 11)
ESTeam Paris Sud/U935 coordinates the National Research Infrastructure INGESTEM (ANR investissement d'Avenir) which is dedicated to the development of reprogramming strategies of adult cells into pluripotent stem cells as well as to the optimal state-of-the art cell differentiation protocols with the goal of modeling human diseases and testing new therapeutic advances. Two main objectives of this program are:
- to provide products and services to the scientific community (public and private; using regional, national or international law)
- to develop R&D programs that will bring new services and innovations developed through entrepreneurship and start-ups or companies with licenses.
The team develops experimental models using state-of-the art technologies on iPS cells connected to research programs integrated in the new Unit. Teams 1, 3 and 4 will join together their respective efforts to promote a rapid transfer of validated concepts using iPS technology to clinical applications as tools for personalized medicine in Onco-Hematology, in liver transplantation and HSC engraftment.