Epithelial stem cells and cancer

Our team aims at deciphering the role of CSC at different step of carcinogenesis from tumor initiation to metastatic spreading in order to prevent and/or override therapeutic resistance. Epithelial cancers are known to present a major intratumoral heterogeneity that contributes to therapy failure and disease progression. The origin of this cellular heterogeneity is mainly explained by a hierarchical organization of tumor tissues where several subpopulations of self-renewing cancer stem cells (CSCs) sustain the long-term oligoclonal maintenance of the neoplasm. CSCs drive tumor growth, resist to conventional therapies and initiate metastasis development. Thus, developing CSC-targeting therapies is becoming a major challenge requiring the understanding of the unique molecular circuitry of CSC as compared to non-CSC. Our research programs focus on three main questions:

  • What is the contribution of lineage-restricted mechanisms that normally maintain epithelium homeostasis during tumor progression?
  • Can we modulate CSC’s intrinsic programs to develop new therapeutic strategies to cure cancer?
  • How essential is the niche in regulating CSC metastatic spreading?


To answer these questions we use two tissue models: the human mammary gland and the epithelial transition zones.

Breast Cancer Program

 

Our team is a pioneer in the identification and characterization of breast cancer stem cells (bCSCs) (Ginestier et al., Cell Stem Cell, 2007; Charafe-Jauffret et al., Cancer Res., 2009). We are pursuing our effort by developing research programs to decipher intrinsic molecular pathways regulating bCSC-fate. We aim at identifying new therapeutic targets to develop anti-CSC therapies. All these translational research programs are based on the development of innovative tools and models (functionnal screens, Patient-derived Xenografts).

 

 

 

 

 

 

Program ''Epithelial Transition Zones''

In detail: visit  http://guaschresearch.info/

In brief: Transition zones represent an abrupt transition between two types of epitheliums, and are ubiquitously found in our body such as in the eye, cervix, between the esophagus and stomach and between the anal canal and rectum. These zones can develop cancer with poor prognosis in human and mouse associated with metastasis. Despite their clinical significance, the underlying molecular and cellular reasons for this tumor susceptibility remain elusive. Our group is using various molecular and biochemistry techniques, flow cytometry, 3D cellular cultures and genetically modified mouse models to characterize these transition zones in normal and pre-lesional states. We are also investigating the role of stem cells and the microenvironment in squamous cell carcinoma development.

 

 

To Work in The Team

 Master and Ph.D student applications are welcome. For the breast model contact christophe.ginestier@inserm.fr and for the transition zone model contact geraldine.guasch-grangeon@inserm.fr.  Postdoctoral applicants eligible to apply for the HFSP, EU Marie Curie and  EMBO fellowships are also welcome.