Phyllis Carolyn Leppert

My Research Interest is the Molecular Biology and development of medical treatments for Uterine fibroids or leiomyomas these are extremely common benign tumors of reproductive age women and are a leading cause of hysterectomy as well as significant morbidity. In addition there are reported racial differences in growth characteristics of fibroids. New studies indicate that uterine fibroids are present in 80% of women of African descent and up to 70-77% in women of European descent. Associated with uterine bleeding and pelvic pain and pressure, they were traditionally thought to be due to the proliferation of smooth muscle cells. However, recent work based on micro-array and on epidemiological data provides evidence that these growths are caused by the accumulation of secretion by the leiomyocyte of altered components of the extracellular matrix, especially collagen. Thus the etiology of these tumors is related to fibrosis in other tissues. Progress has been made in identify the pathways leading to the accumulation of altered extracellular matrix in these tumors. The most important are 1) fibroids are similar in matrix composition to skin keloids, a type of altered wound healing. 2) Progesterone partial antagonists cause significant reduction in the size of uterine fibroids and in reduction of the uterine bleeding associated with them 3) differential gene expression demonstrates defined molecular subtypes. Translational research in my laboratory focuses on the thrombospondin 1 as a modulator of angiogenesis in uterine tumors and on the initiation of the differentiation of the myocyte to leiomyocyte leading to the altered secretion of collagen and other components of the matrix and to the role of mechanotransduction in the etiology of uterine fibroids. My research also focuses on Clinical Trials of drug treatment regimens for fibroids.