BRIGHAM AND WOMEN'S HOSPITAL, INC., THE
Grant: $105,987 - National Institutes of Health - Aug. 31, 2009
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Award Description: p53 signatures and pelvic serous carcinoma
Project Description: The following have been achieved in the past three months: 1) A model for the p53 signature has been constructed using the Li Fraumeni syndrome. We disoovered a high rate of p53 signatures in these patients and have described a step-wise carcinogenic pathway (Xian et al, J of Pathol, in press). 2) We have isolated p53 signatures in frozen sections of normal fallopian tubes, have isolated RNA by laser capture microdissection and are interrogating the array data to identify biomarkers linked to and and pathways perturbed in this precursor. 3) We have establsihed primary cell cultures of fallopian tube epithelium from women with both BRCA1 mutations and Li Fraumeni syndrome and will soon be manipulating these cells to reproduce the early events in serous carcinogenesis in vitro. 4) In collaboration with Michael Birrr, we have established expression profiles from distal fallopian tubes of women with malignancy (n=10) and normal controls (n=10) and have identified a unique set of 200+ genes which distinguish the normal tubal mucosa from these two entities. The goal is to take this data set and test it against prospectively accrued samples to determine if there is a tubal 'expression signature' that will segregate with ovarian cancer risk.
Jobs Summary: The laboratory of the PI is engaged in the development of a novel model for ovarian carcinogenesis that originates in the distal fallopian tube (the p53 signature). This discovery and its integration into the general model of ovarian carcinogesis, has been viewed as a paradigm shift in the field and one that will impact on both our understanding of how these tumors develop and strategies for ovarian cancer prevention and detectino. The purpose of the original award was to study a putative precursor to serous cancer, the 'p53 signature'. This entity was described by the PI in several publications and the award was designed to study this entity in cell culture, generate expression data from these microscopic precursor lesions, and identify candidate genes that could facilitate the detection of early serous cancers. Progress on all of these goals has been made. As of July 1, 2009, the PI employed one full-time research associated (Wa Xian), a full-time research fellow (Karishma Mehra) and soon after took on a volunteer (Mitra Mehrad) to conduct this project. The funding has made it possible to retain Wa Xian at 30% as a research associate so that she can continue training the other two members of the current laboratory over the next 12 months and develop collaborations critical to the project. The funds encumbered for Dr Xian have freed up sufficient departmental funds to provide Mitra Mehrad, an unemployed volunteer research fellow, with health insurance during her stay in the laboratory next year. The funding also carries a subcontract to Alexander Miron at the Dana Farber Cancer Institute, to cover salary in his laboratory. (Total jobs reported: 0)
Project Status: Less Than 50% Completed
This award's data was last updated on Aug. 31, 2009. Help expand these official descriptions using the wiki below.
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