Transitional zone

Merging microenvironments Stem cells & Cancer

About

Research Background

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.

Team

EPITHELIAL STEM CELLS AND CANCER

Charafe-Jauffret E., Ginestier C.

Principal Investigator

Géraldine Guasch, Ph.D, HDR

Permanent Research Engineer

Véronique Chevrier, Ph.D

MD INTERN IN DIGESTIVE SURGERY

Victoria Weets, MD

PhD Student Oncology

Chloé Petitpas

Master 2 Pro Aix-Marseille University

Simon Triaire

Master 2, Aix-Marseille University

Fiona Lucia

Engineer (IE)

Marjorie Martin

Engineer (IE)

Solène Mathieu

MD intern in digestive surgery

Julien Bonnet

Master 1

Sonia Rolo

Post-doctoral student

Louciné Mitoyan

Engineer (IE)

Alexane Ollivier

MD intern in digestive surgery

Eddy Traversari

Engineer (IE)

Manon Saubin

A video presentation of 3D HubO Platform for Stem Cell and Organoid Medicine. This video was made possible by the Institute Cancer and Immunology (ICI).

Our lab’s pictures

Lab party under the rain… and then the sun to celebrate our latest publication! #teambuilding

Professor Michael Rendl working on hair follicle development from Mount Sinai New York has visited us in May 2019

Visit Rendl Laboratory

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

”Find the pink stars”: LOUCINÉ and GÉRALDINE at the Gordon Research International Conference in July 2019

Latest news

New publication

Jun 1, 2022

The Hub-O platform got the Canceropole PACA and Ibisa labels

Jan 17, 2022

Online training: CIVIS Cancer et Immunology Mobility Network.

Sep 1st, 2021

Talk with Dr. Cécile de Chaisemartin at the Annual Seminar of the Canceropole SUD at the Translational Session

July 1st, 2021

A new publication highlighted by the Paoli Calmettes Institute

May 19th, 2021

A new physiological platform for research on living disease tissue called ‘’3D-Hub-O Platform’’ to be launched on January 2020

Jan 1st, 2020

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

Resources

3D-Hub-O Platform

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

network

Institut Fresnel
http://www.fresnel.fr/spip

FSSCR: Member of the Société Française de Recherche sur les Cellules Souches
http://fsscr.fr

Former member of the International Society for Stem Cell Research
http://www.isscr.org

Adjunct Assistant Professor in the Developmental Biology Department at Cincinnati Children’s Hospital
https://www.cincinnatichildrens.org/research/divisions/d/dev-biology

Former Research Associate at The Rockefeller University, New York
http://www.rockefeller.edu

City University of Hong Kong
http://www.cityu.edu.hk/bms/

Technology Platforms

IPC/CRCM Experimental Pathology Platform (ICEP)

SFR Biosciences Virus production Platform

Microscopy and Scientific Imaging Platform (MISc)

Flow Cytometry and Fluorescence-activated cell sorting Platform

Most relevant publications to the current projects

Richart L, Picod-Chedotel ML, Wassef M, Macario M, Aflaki S, Salvador MA, Héry T, Dauphin A, Wicinski J, Chevrier V, Pastor S, Guittard G, Le Cam S, Kamhawi H, Castellano R, Guasch G, Charafe-Jauffret E, Heard E, Margueron R, Ginestier C.

XIST loss impairs mammary stem cell differentiation and increases tumorigenicity through Mediator hyperactivation. Cell. 2022 Jun 9;185(12):2164-2183.e25.

Mitoyan L, Chevrier V, Hernandez-Vargas H, Ollivier A, Homayed Z, Pannequin J, Poizat F, De Biasi-Cador C, Charafe-Jauffret E, Ginestier C, and Guasch G.

A stem cell population at the anorectal junction maintains homeostasis and participates in tissue regeneration after injury. Nature Communications 2021 12(1):2761.

Alexane Ollivier, Maxime Mahé, Guasch G.

Modeling gastrointestinal diseases using organoids to understand healing and regenerative processes. Cells. 2021,10, 1331

McCauley HA., Guasch G.

Isolation and separation of epithelial CD34+ cancer stem cells from Tgfbr2-deficient squamous cell carcinoma. Bio-protocol. 2017

McCauley HA., Chevrier V., Birnbaum D., Guasch G.

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.

McCauley HA., Guasch G.

Serial orthotopic transplantation of epithelial tumors in single-cell suspension. Methods Mol Biol. 2013. 1035:231-45.

McNairn A., Guasch G

Epithelial Transition Zones: merging microenvironments, niches, and cellular transformation. European Journal of Dermatology. 2011, 21(Suppl.2):21-28. Review.

Runck L., Kramer M., Ciraolo G., Lewis A., Guasch G.

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.

Guasch G Schober M., Pasolli A., Conn E., Polak L., Fuchs E.

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.

Tumbar T., Guasch G., Greco V., Blanpain C., Lowry W., Rendl M., Fuchs E.

Defining the epithelial stem cell niche in skin. Science. 2004, 303: 359-363.

Fuchs E., Tumbar T., Guasch G.

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.

Short talk at the regenerative medicine – Organoids and model species – symposium

October, 8th 2018

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 geraldine.guasch-grangeon@inserm.fr

Jan 15th, 2020

Le cancer colorectal : Quelle autonomie de choix pour les patients? Institut Paoli-Calmettes – Marseille

November, 23rd 2018

Geraldine Guasch is scheduled for a talk at the Epithelial Differentiation and Keratinization Gordon Research Conference

July 7-12th, 2019

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.

October, 2018

Dr Géraldine GUASCH to give a presentation on “Animal Models” at the next SUNRiSE (Solid Tumor Cancer Stem Cell) network training session.

June, 2018

Louciné Mitoyan representing the lab and CRCM at the 3rd edition of the Aldelih congress. Thank you Dr Cédric Blanpain for your support!

March, 2018

Stem cells in solid tumors : from biology to therapeutics

November, 2017

Isolation and Separation of Epithelial CD34+ Cancer Stem Cells from Tgfbr2-deficient Squamous Cell Carcinoma

September, 2017