Harvard Catalyst Profiles

Molecular interrogation of gynecologic tumors:
My group molecularly interrogates gynecologic tumors to identify genes or proteins and their corresponding signaling pathways that contribute to malignant transformation, the pathology of the disease, recurrence and/or resistance to therapy. Once key factors or pathways are identified, we actively test novel anticancer drugs to determine their efficacy in tumor explant models. In addition, we assess the efficacy of dual or sequential therapy. Specifically, we assess whether novel anti-cancer agents work better as a single agent or in conjunction with the standard of care or another anti-cancer agent.

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.

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. More recently, Dr. Styer and I embarked on an in depth study to assess irregular microRNA (miRNA) expression in leiomyomata compared to matched native myometrium. As a result of these preliminary studies, we have begun in vitro functional studies in primary and immortalized fibroid and myometrial cells. Our ultimate goal is to delineate the functional impact of leiomyoma miRNA expression in the genesis, progression and phenotypic characteristics of the disease. In addition, we anticipate we may uncover novel gene targets that will serve in the development of alternative uterine sparing treatment strategies.

Drug development for treatment of resistant gynecologic cancers:
As a result of our multiple interactions with pharmaceutical companies we have become more proactive in formulating stronger collaborations with the intent to develop novel inhibitors of oncogenic pathways, identify susceptible immune checkpoints, test new immune treatment strategies, and generate specific antibody drug conjugates for the treatment of women diagnosed with endometrial or ovarian cancer.

• Cancer Stem Cells
• Glycosylation
• Ovarian Cancer
• Uterine Cancers
• cell signaling
• Drug Resistance
• primary derived xenograft
• S Phase Kinase Associated Proteins