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

Principal Investigator

Géraldine Guasch, Ph.D, HDR

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Permanent Research Engineer

Permanent Research Engineer

Véronique Chevrier, Ph.D

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PhD Student Human Pathology / Oncology

PhD Student Human Pathology / Oncology

Louciné Mitoyan

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Master 1 student Human Pathology

Master 1 student Human Pathology

Sonia Rolo

Lab’s life

Dr Geraldine GUASCH invites young investigators from all over the world to come and work in Marseille

Latest news

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


June, 2018

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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

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9th grader student Maud Willermoz participated in our research as part of the orientation program promoted by the Ministry of National Education.


December, 2017

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SFC (Société Française du Cancer) training

Stem cells in solid tumors : from biology to therapeutics

November, 2017

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Research projects

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

Characterization of the molecular mechanisms involved in the metastatic properties of cancer stem cells of the transition zone.

Cancer Stem Cells Regulation in transition zone by their niche.

Define the pre-tumoral niche of transition zones susceptible to develop metastatic carcinoma. In vitro and in vivo study of the molecular mechanisms involved in the interaction between fibroblasts and cancer stem cells at the transition zone. Define the properties of transition zone fibroblasts in human cancer.

Transition zone Cancers biobank

Collaboration with pathologists at the Paoli Calmettes Institute and at the Hopital Nord HP-HM to establish a unique collection of transition zone tumors (cervix, anorectal, esophagus-stomach)

Development and Transition Zone

Define the origin of transition zone and the role of stem cells in tissue homeostasis

Resources

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

Publications

Most relevant publications to the current projects
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. ELife2017. 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.

Archives

New publication

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

September, 2017

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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

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New Chapter Book:

Biology and Engineering of Stem Cells Niches. 1st edition

April, 2017

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New Publication by our lab :

A new mechanism connects the loss of TGFβ signaling with invasion and metastasis in highly malignant transition zone tumors.

February, 2017

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Invited Talk at the Erasmus University Medical Center in the Department of Cell Biology, Rotterdam

October, 2016

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Invited Talk at the City University of Hong Kong in the Department of Biomedical Sciences, Hong Kong

August, 2016

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Gordon Research Conference “Tissue Niches & Resident Stem Cells in Adult Epithelia”

August, 2016

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Contact

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