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Our laboratory has a longstanding interest in understanding the earliest phases of tumor formation. This led us to study stem cell biology with a focus on two fundamental questions:
We are focusing on epithelial tissues such as the mammalian skin, and its appendages, the sebaceous / sweat glands, and the transition zone that lies between the skin and the anal epithelium (figure 1). Our research has identified an unsuspected link between the normal stem cell of the skin and an abnormally high incidence of tumors that arise in the transition zone in that both are regulated by the TGFβ signaling pathway. Our laboratory now uses the transition zone as a unique model to investigate the molecular basis for how normal epithelial stem cells might become cancer stem cells.
Being part of a pediatric medical center, we have established a research program that toggles between basic discoveries of stem cell biology and several clinical programs here, including oncology, skin engineering and anorectal malformations.
We use a variety of molecular, biochemical and tissue culture techniques, in vivo imaging and fluorescence-activated cell sorting, as well as mouse transgenic and gene targeting (knockout) technology to address these various questions.
The Guasch lab was recently awarded the NIH Digestive Health Center Grant, P30 DK078392 for the project titled: Using the Shh knock out mouse model to investigate the mechanism of persistent cloaca in human. 06/01/2012-05/31/2013.
Dr. Geraldine Guasch won the Cancer Research V Scholar Award competition 2011. She is one of the 14 national recipients of this prestigious Award. The grant is $200,000, two-year commitments. The V Foundation funds grants to the brightest physicians and scientists as they pioneer techniques to make breakthroughs in cancer research. Dr. Guasch is investigating whether a population of epithelial cells with stem cell properties is involved in the formation and maintenance of transitional zone tumors
Our lab has won a Sidney Kimmel Scholars Award which provides research grants to the nation's most promising young cancer researchers. The goal of the grant program is to improve the basic understanding of cancer biology and to develop new methods for the prevention and treatment of cancer. The Sidney Kimmel Foundation for Cancer Research has selected fifteen scientists from across the United States to receive two year grants in the amount of $200,000 under the Foundation's on-going Kimmel Scholar program. Dr. Guasch is the first Awardee from Cincinnati Children's.
Other grants include:
McNairn AJ, Brusadelli M, Guasch G. Signaling moderation: TGF-β in exocrine gland development, maintenance, and regulation. Eur J Dermatol. 2013 Apr 10.
Chang CY, Pasolli HA, Giannopoulou EG, Guasch G, Gronostajski RM, Elemento O, Fuchs E. NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche. Nature. Mar 7 2013.
McNairn AJ, Doucet Y, Demaude J, Brusadelli M, Gordon CB, Uribe-Rivera A, Lambert PF, Bouez C, Breton L, Guasch G. TGFβ signaling regulates lipogenesis in human sebaceous glands cells. BMC Dermatol. 2013.
McCauley, H.A. and Guasch G. Serial orthotopic transplantation of epithelial tumors in single-cell suspension. Methods Mol Biol: Stem Cells and Niche, in press.
Guasch G, Schober M, Pasolli A, Conn E, Polak L, Fuchs E. Loss of TGFbeta signalling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia. Cancer Cell. 12:313-27. 2007.
*Li J, *Greco V, *Guasch G, Fuchs E, Mombaert P. Mice cloned from skin cells. Proc Natl Acad Sci USA. 104: 2738-43. (* contributed equally to this work). 2007.
Lowry W, Blanpain C, Nowak J, Guasch G, Lewis L, Fuchs E. Defining the impact of β-catenin/Tcf transactivation on epithelial stem cells. Genes & Dev. 13:1596-611. 2005.
Guasch G, Fuchs E. Mice in the world of stem cell biology. Nature Genetics. 37(11):1201-6. 2005.
Tumbar T, Guasch G, Greco V, Blanpain C, Lowry W, Rendl M, Fuchs E. Defining the epithelial stem cell niche in skin. Science. 303:359-63. 2004.
Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell. 116: 769-78. 2004.
Guasch G, Delaval B, Arnoulet C, Xie MJ, Xerri L, Sainty D, Birnbaum D, Pebusque MJ. FOP-FGFR1 tyrosine kinase, the product of a t(6;8) translocation, induces a fatal myeloproliferative disease in mice. Blood.103:309-12. 2004.
Guasch G, Popovici C, Chaffanet M, Mugneret F, Pontarotti P, Birnbaum D, Pébusque M.J. Endogenous retroviral sequence is fused to FGFR1 kinase in the 8p12 stem cell myeloproliferative disorder with t(8;19)(p12;q13.3). Blood. 101:286-8. 2003.
Guasch G, Ollendorff V, Borg JP, Birnbaum D, Pébusque M-J. 8p12 stem cell myeloproliferative disorder: the FOP-Fibroblast growth factor receptor 1 fusion protein of the t(6;8) translocation induces cell survival mediated by mitogen-activated protein kinase and phosphatidylinositol 3-Kinase/AKT/mTOR pathways. Mol Cell Biol. 21:8129-42. 2001.
click to enlarge
The Anorectal Transitional Epithelium: an Abrupt Transition
Keratin 17 (red) stains the transitional zone between the stratified anal canal and the simple epithelium of the intestine of a wild-type mouse.
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