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Geraldine Guasch, PhDAssistant ProfessorDepartment of Pediatrics; Division of Developmental BiologyVisit the Guasch Lab Site
Dr. Guasch’s research interest is to define the properties of the cells located at the epithelial transitional zones (TZs) where two cell types meet. TZs are found throughout the body and are defined by the abrupt change of one type of epithelium to another (stratified to simple epithelium for example). Dr. Guasch’s long-term goal is to understand the molecular mechanism underlying tumor susceptibility in TZs. She has recently developed a mouse model for epithelial anogenital cancers using the Keratin 14 promoter. Mice conditionally targeted for the transforming growth factor-β receptor-II developed spontaneous squamous cell carcinomas (SCCs) in their anal and genital region, while deficient backskin appeared morphologically normal. Specifically, spontaneous SCCs frequently arose within TZs where the stratified squamous epithelium of the anal canal meets the simple epithelium of the dentate line that connects the colon-type mucosa. It is possible that cells within this region are intrinsically more prone to transformation or alternatively, that the environment is permissive for transformed cells. To achieve Dr. Guasch’s long-term goal she will investigate the intrinsic properties of these cells and their interactions with the neighboring cells and she will characterize the role of these cells in a mouse model of transitional epithelia tumor. She will address if normal resident adult tissue stem cells from the anal transitional epithelium may be a special target for carcinogenic insults. Dr. Guasch devised an innovative strategy in mice to isolate stem cells from any tissue of interest based on their slow-cycling property. This model solves a major problem in stem cell biology by enabling the isolation of specific cell types despite the absence cell surface markers. Using this model Dr. Guasch recently showed that slow-cycling cells are present in transitional epithelium frequently associated with tumor formation.
Dr. Guasch will use the Gene Expression and Bioinformatics Core in collaboration with Dr. Aronow to develop a microRNA database for the anorectal junction that may be part of a complete microRNA database on GI development. She will also use the Morphology Core to investigate the role of TZ cells in tumorigenesis.
Click image to enlarge
Cells from tetracycline-regulatable histone H2B-GFP transgenic mice colocalize with BrdU-retaining cells. (A) Schematic of BrdU and doxy pulse-chase experiments. (B–E) Colocalization of BrdU and H2B-GFP before (B and C) and after the chase (D and E. After the chase, white arrows indicated label-retaining cells in the bulge of the perianal hair follicle (D) and in the basal layer of the anal TZ (E). Figure from Cell Cycle, 2010;9:3039-3045.
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