Dr. Fazleabas has been funded continuously by the National Institutes of health in the USA since 1986 for studies using the baboon as a model for reproductive biology research. The work in his laboratory has significant translational relevance related to improved pregnancy outcomes in infertile women as well as understanding the etiology and the pathophysiology associated with the development of endometriosis. His laboratory was the first to demonstrate that chorionic gonadotropin acts directly on the uterus in vivo and using this “simulated pregnancy model” went on to demonstrate that the early luteotrophic signal from the primate embryo is critical for initiating the decidualization response and remodeling the luminal epithelium to enhance trophoblast invasion. Recent studies have shown that infusion of chorionic gonadotropin in women undergoing assisted reproductive therapies improves the endometrial environment to facilitate the successful establishment of pregnancy. His laboratory has also published extensively on morphological changes associated with early placental development and the interaction between placental attachment and endometrial transformation. These initial studies have led to the more recent extensive studies related to embryo implantation and maternal fetal interactions and have focused specifically on the role of Notch 1 during the process of decidualization. In addition to studies in the non-human primate and in stromal cells from women, his laboratory has also developed novel transgenic models which have cell specific gain of function and loss of function properties to study the role of Notch signaling in decidualization and endometriosis. In addition to the basic fundamental role that Notch1 plays in initiating the decidualization process, recent data from the laboratory also suggests that altered Notch signaling as a consequence of endometriosis, which is a disease that affects 176 million women worldwide, has a significant impact on an aberrant decidualization response in the eutopic endometrium and promotes lesions development at ectopic sites. The focus of these studies are to understand the fundamental mechanisms by which Notch1 interacts with FOXO1 and progesterone to promote decidualization and the implications of altered Notch1 signaling in contributing to the pathophysiology of endometriosis. In conjunction with the studies on the role of Notch signaling in the pathophysiology of endometriosis, his laboratory has also identified specific microRNA’s that are altered in both the ectopic and eutopic tissues of baboons and women with endometriosis. These studies have specifically focused on target genes that are regulated my microRNA’s 451, 29c and 21 which in turn contribute to enhanced proliferation, suppression of apoptosis, development of progesterone resistance and fibrosis, which are all hallmarks of endometriosis related pathologies. He has over 200 peer reviewed publications and has authored multiple book chapters and reviews. The full list of publications is available at http://www.ncbi.nlm.nih.gov/pubmed/?term=Fazleabas.

Research Summary