Asgerally Fazleabas

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. A significant area of his research emphasis has been to study the early events associated with maternal-fetal interactions during the establishment of pregnancy and the mechanisms by which these interactions are affected in women and non-human primates with endometriosis.

His laboratory was the first to demonstrate that endometrial responses to chorionic gonadotropin are attenuated in endometriosis as a consequence of progesterone resistance. 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 endometriosis. Recent data from the laboratory suggests that the inflammatory cytokine IL-6 transcriptionally regulates NOTCH expression via the induction of E-Box proteins.

In conjunction with the studies on the role of Notch signaling in the pathophysiology of endometriosis, his laboratory has developed a novel spheroid system that mimics the peritoneal environment in vitro and shown that these endometriotic organoids have a transcriptomic signature similar to spontaneous endometriotic lesions in the baboon. These transcriptomic analyses have also demonstrated that the baboon lesions have significant transcriptomic overlap with lesions obtained from adolescent women. Recent work using spatial transcriptomics have revealed novel cross talks within the endometriotic lesion between macrophages and the epithelial cells suggesting potential avenues for targeted discovery and non-hormonal therapies.