Sylvester Comprehensive Cancer Center

Sophia George, Ph.D.

Sophia George, Ph.D.

Research Assistant Professor of Obstetrics & Gynecology

Description of Research

Molecular/genetic changes present in morphologically normal fimbrial epithelium in BRCA1 mutation carriers reflect the earliest alterations in serous carcinogenesis, and manipulation of selected genes in an in vitro culture model preferentially induce a tumorigenic phenotype in Fallopian Tube Epithelium (FTE) cells. It is thought that secretory cells are the cells of origin of High-Grade Serous Carcinoma (HGSC) but not much is known about the contribution of ciliated FTE cells or the ‘peg’ cells, or the biology of the FTE progenitor cells and how they contribute to the HGSC disease development. Along with transcriptional and translational changes within this high-risk population, miRNA/lncRNA signatures and chromatin remodeling changes in breast and fallopian tube epithelial cells of these genetically high-risk women.

The fallopian tube epithelial layer is thought to be the drivers in both low-grade and high-grade serous carcinoma. These cells are exposed to a series of hormonal and inflammatory bursts from menarche to menopause in women. These environmental factors are thought to trigger genetic events which leads to the aggressive phenotype observed in high-grade serous cancer. Profiling and modeling neoplastic lesions of both these diseases will give insight into carcinogenesis and potential avenues for targeted therapy.

Highlights

  • Demonstrated transcriptional differences between the fallopian tube epithelial layer of BRCA1 mutation carriers and non-carriers.
  • Demonstrated the infiltration of immune cells into pre neoplastic and neoplastic lesions found in the fimbria correlates with disease progression.
  • Identified a minimal deletion region on Chr 19p13.3 correlates with improved progression free survival and overall survival in high-grade serous cancer patients.
  • Used ex-vivo culture of fallopian tube epithelium to model pre-neoplastic changes observed in the fallopian tubes of BRCA1/2 mutation carriers.
  • Member of a collaborative team assessing the type and prevalence of germ-line mutations in hereditary breast and ovarian cancer genes in 6 countries in the Caribbean.

Selected Cancer-Related Publications

Programs

Collaborating in the Multidisciplinary Research Program(s):

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