My laboratory generated the first genetically defined model from transformed human ovarian epithelial cells, and we were among the first to define the key autocrine and paracrine mechanisms between epithelial cells and senescent stromal cells for ovarian cancer progression. More recently, my laboratory has made the surprising finding that polyploid giant cancer cells (PGCCs), generally believed to be non-dividing senescent cancer cells, can dedifferentiate into blastomere-like cancer stem cells, the earliest stage of embryonic development. The reprogramming is achieved via a novel cellular mechanism we term the giant cell cycle. PGCCs represent the most archaic cancer stem cells reported to date. I was principal investigator (PI) of a NIH-funded R01 grant and am co-investigator of several other NIH grants related to ovarian cancer. I am also co-PI of the tissue pathology core for MD Anderson’s SPORE in ovarian cancer and PI of multi-investigator grants from the Cancer Prevention Research Institute of Texas. I also direct the core resource for patient-derived xenografts (PDXs) for ovarian cancer and have established a cohort of more than 40 ovarian cancer PDX models and are in the process to develop organoids from each model and primary cancer. The overall goal of this proposal is to understand the molecular mechanisms regulating the growth and division of PGCCs and identify combinations of novel therapeutic agents to block PGCC growth and division in synergy with paclitaxel in ovarian PDX models. I have successfully administrated a productive research group for the past 18 years, and have collaborated with many investigators. In summary, I have a strong background in pathology and a productive research program in ovarian cancer. Together with our co-investigators, our team has all of the expertise needed to successfully carry out the proposed work.