Investigation into the functional significance of the functional contribution of gynecologic cancer stem cells: My group has extensively studied and continues to conduct research focused on the functional contribution of sub populations of gynecologic cancer cells that have stem like characteristics a contributing to the pathology and high recurrence rate. Our research provided valuable rationale for identifying targetable cells and testing combination therapies that can be tested in clinical trials for women with recurrent and refractory gynecologic cancer.
Investigation into the functional significance of aberrant forms of glycosylation in gynecologic cancers: Tumor-associated carbohydrate antigens (TACAs) are promising therapeutic targets. Increased presence of Sialyl-Thomsen-nouveau antigen (STn), a TACA, correlates with worsened outcome and chemoresistance in ovarian cancer (OvCa). However, our recent studies suggest that many of the previous published reports that supported this conclusion utilized STn antibodies that may not be as specific as originally proposed. We are working with a panel of murine and humanized antibodies that bind with high specificity to all glycoforms of STn. Our preliminary data utilizing these novel highly specific STn antibodies suggests that STn is present in a significant subset of OvCa cells and tumors. From a therapeutic standpoint, we are testing STn-antibody drug conjugates (ADC) in in vitro and in vivo models.
Define mechanisms that contribute to the genesis, progression or pathology of benign gynecologic diseases: In addition to in depth studies on gynecologic malignances we also focus on benign diseases that impact reproductive aged women. Specifically, we have and continue to be focused on endometriosis and leiomyoma. These non-malignant diseases can have a devastating negative impact on women’s health and quality of life. Despite the prevalence of the disease very little progress have been made in long term solutions with the exception of surgical removal of the of uterus. We have used mouse models as well as primary human tissues to assess the mechanisms by which specific cell signaling factors positively or negatively impact the development, progression and/or pathological properties associated with these diseases.