My Research
KEYWORDS
translational medicine, hormonal carcinogenesis, normal and malignant growth regulatory mechanisms, post-translational protein modifications, cell cycle, ubiquitin pathway regulation of growth, TGF-β signaling, stromal/epithelial interactions and cell substrate interactions in cancer…
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SUMMARY
Cancer Biology:

The laboratory studies loss of growth regulation in cancer, particularly hormone-regulated cancers. Specific objectives emphasize alterations in cancer cells with respect to the regulation of cell cycle proteins by ubiquitin-mediated degradation, nuclear-cytoplasmic shuttling of cell cycle proteins, growth factor signaling pathways, particularly TGF-β, hormone-regulated growth, and stromal/epithelial interactions. For example, we are the first to show that TGF-β, estrogen, and progesterone control endometrial epithelial cell proliferation by regulating the protein levels of the cyclin-dependent kinase inhibitor, p27kip1 (p27) through the ubiquitin pathway (Diagram). Therefore, identifying specific inhibitors of the E3 ligase, Skp2 to potentially prevent p27 degradation to regain growth control is a potential specific therapy for endometrial carcinoma and other human cancers showing loss of nuclear p27. We utilize epithelial and stromal cells, isolated from normal and malignant endometrium, in primary cultures, co-cultures, and 3-dimensional matrices as our major model systems. These physiological paradigms afford optimal approaches to understanding the role of stromal cells surrounding malignant glands in malignant progression (tumor microenvironment) and a greater probability for defining molecular targets for translation into novel treatments for cancer prevention and therapy.