Associate Professor, Department of Medicine
Associate Professor, Department of Pathology
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.
We discovered that the intracellular calcium-binding endoplasmic reticulum (ER) chaperone protein, calreticulin has non-ER functions of topically enhancing the rate and quality of wound healing and exogenously, inducing proliferation, migration, and matrix protein induction of cells involved in the wound healing process. The mechanisms involved in how calreticulin induces these functions from the outside-inward and the receptors are unknown opening a new area for the lab to explore.
Permanent member of Metabolic Pathology and Tumor Cell Biology IRGs, NIH; Council, American Association Cancer Research (WICR), SEP Review Panel for Gynecological SPORE, NIH; Review Panel for AACR Fellowships, Ad hoc Reviewer for numerous IRGs, NIH; Associate Editor, Molecular Signaling.
FASEB journal. 2020 Dec; 34(12):15849-15874
International journal of molecular sciences. 2019 Jan 18; 20(2):
Endocrinology. 2017 09 01; 158(9):2754-2773
International journal of biochemistry & cell biology. 2017 08; 89:199-206
Cell stress chaperones. 2015 Nov; 20(6):875-83
Microbial cell factories. 2015 Oct 15; 14:165