Merging microenvironments Stem cells & Cancer
Epithelia constitute the surfaces and lining of our bodies and provide a protective envelope against external environment but also regulate water, nutrient absorption and glandular secretions.
Although epithelia can be multilayered (stratified) or single-layered (simple) they both need to constantly replace damaged or dead cells during the life. Adult stem cells are responsible for this process of tissue homeostasis critical for the maintenance of the tissue. At certain location of the body, transition zone lies between two types of epithelium. These transition zones are found in the eye, oesophagus, stomach, ovary, cervix and anus. In human, these junctions are highly susceptible to tumor formation and the interest of my laboratory is to identify the underlying molecular and cellular basis for this tumor susceptibility. We are investigating the intrinsic properties of these transitional epithelial cells and their interactions with the neighboring cells. We hypothesize that cells within this region are intrinsically more prone to transformation or alternatively, that the environment is permissive for transformed cells.
EPITHELIAL STEM CELLS AND CANCER
Charafe-Jauffret E., Ginestier C.
Géraldine Guasch, Ph.D, HDRread more
Permanent Research Engineer
Véronique Chevrier, Ph.DRead more
PhD Student Human Pathology / Oncology
Louciné MitoyanRead more
Alexane OllivierRead more
MD intern in digestive surgery
Julien BonnetRead more
Sonia RoloRead more
A la rencontre du monde des chirurgiens, personnel médical, patients pour discuter de la politique de santé et des perspectives dans le dépistage du cancer colorectal – Crédits photo & COPYRIGHT IPC, MICHEL GELABERT
Débats publics de l’Institut Paoli Calmettes
Our group is recruiting a post-doc interested in using single cell sequencing of transition zone early stage tumors and organoid technology to characterize the pre-tumoral immune environment. Interested? Please send your application to email@example.com
Jan 15th, 2020
A new physiological platform for research on living disease tissue called ‘’3D-Hub-O Platform’’ to be launched on January 2020
Jan 1st, 2020
Geraldine Guasch is scheduled for a talk at the Epithelial Differentiation and Keratinization Gordon Research Conference
July 7-12th, 2019
Le cancer colorectal : Quelle autonomie de choix pour les patients? Institut Paoli-Calmettes – Marseille
November, 23rd 2018
Short talk at the regenerative medicine – Organoids and model species – symposium
October, 8th 2018
Epithelial tissues are maintained through life by stem cells.
We have recently identified an unrecognized stem cell niche at the junction area between two epithelium, called transition zone frequently associated with cancer with poor prognosis. Our group studies the role of these cells in transition zones in cellular homeostasis and tumorigenesis.
Cancer Stem Cells Transition Zone
Cancer Stem Cells Regulation in transition zone by their niche.
Transition zone Cancers biobank
Development and Transition Zone
With the financial help of the Canceropole PACA, a first-in-class physiological platform for research on living disease tissue called ‘’3D-Hub-O Platform’’ located at the CRCM (Marseille) will be available to researchers in January 2020.
Led by Dr. Guasch (scientific director) and Dr. Chevrier (technical director), the platform will focus on three main objectives
- To generate human organs to study and cure disease
- To generate patient-derived organoid (PDO) biobank for precision medicine
- To generate human organs and tumors with a working microenvironment
FSSCR: Member of the Société Française de Recherche sur les Cellules Souches
Former member of the International Society for Stem Cell Research
Adjunct Assistant Professor in the Developmental Biology Department at Cincinnati Children’s Hospital
Former Research Associate at The Rockefeller University, New York
City University of Hong Kong
Most relevant publications to the current projects
Isolation and separation of epithelial CD34+ cancer stem cells from Tgfbr2-deficient squamous cell carcinoma. Bio-protocol. 2017
De-repression of the RAC activator ELMO1 in cancer stem cells drives progression of TGFβ-deficient squamous cell carcinoma from transition zones. ELife. 2017. pii: e22914.
Serial orthotopic transplantation of epithelial tumors in single-cell suspension. Methods Mol Biol. 2013. 1035:231-45.
Epithelial Transition Zones: merging microenvironments, niches, and cellular transformation. European Journal of Dermatology. 2011, 21(Suppl.2):21-28. Review.
Identification of epithelial label-retaining cells at the transition between the anal canal and the rectum in mice. Cell Cycle. 2010, 15: 3039-3045. Cover Article.
Loss of TGFβ signalling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia. Cancer Cell. 2007, 12: 313-327. Featured Article
Highlighted by: Wakefield LM et al., Cancer Cell. 2007, 12: 313-327.
Defining the epithelial stem cell niche in skin. Science. 2004, 303: 359-363.
Socializing with the neighbors: stem cells and their niche. Cell. 2004, 116: 769-778. Review.
Additional recent publications of importance to the field
McCauley, HA. and Guasch G
Three Cheers For The Goblet Cell: Maintaining Homeostasis In Mucosal Epithelia. Trends In Molecular Medicine, 2015 Jul 3. pii: S1471-4914(15)00120-3. Revue. Cover
McCauley HA, Liu C-Y, Attia A, Wikenheiser-Brokamp KA, Zhang Y, Whitsett JA, and Guasch G.
TGFβ signaling inhibits goblet cell differentiation via SPDEF in the conjunctival epithelium. Development. 2014 141:4628-4639.
Gupta A., Bischoff A., Peňa A., Runck L.A., Guasch G
The Great divide: septation and malformation of the cloaca, and its implications for surgeons. Pediat Surg Int. 2014, 30(11):1089-95.
Runck LA, Method A, Bischoff A, Levitt M, Peña A, Collins M, Gupta A, Shanmukhappa S, Wells J.M, Guasch G.
Defining the molecular pathologies in cloaca malformation: similarities between mouse and human. Dis Model Mech. 2014, 7(4):483-93.
Interested to collaborate with a French laboratory and obtain an international experience? The call for applications for the Chateaubriand Fellowship is open every year from October to January.
Dr Géraldine GUASCH to give a presentation on “Animal Models” at the next SUNRiSE (Solid Tumor Cancer Stem Cell) network training session.
Louciné Mitoyan representing the lab and CRCM at the 3rd edition of the Aldelih congress. Thank you Dr Cédric Blanpain for your support!
SFC (Société Française du Cancer) training
Stem cells in solid tumors : from biology to therapeutics
Isolation and Separation of Epithelial CD34+ Cancer Stem Cells from Tgfbr2-deficient Squamous Cell Carcinoma
External Seminar at the Developmental Biology Institute of Marseille (IBDM) :
Transitional zones: merging microenvironments, stem cells and cancer Invitation : A. Le Bivic
April 7th, 2017
New Chapter Book:
Biology and Engineering of Stem Cells Niches. 1st edition
New Publication by our lab :
A new mechanism connects the loss of TGFβ signaling with invasion and metastasis in highly malignant transition zone tumors.
Invited Talk at the Erasmus University Medical Center in the Department of Cell Biology, Rotterdam
Invited Talk at the City University of Hong Kong in the Department of Biomedical Sciences, Hong Kong
August, 2016Read more
Gordon Research Conference “Tissue Niches & Resident Stem Cells in Adult Epithelia”
August, 2016Read More
9th grader student Maud Willermoz participated in our research as part of the orientation program promoted by the Ministry of National Education.
Stay in touch!