2024 Early Career Investigator Grant Recipient — Nicole James, PhD
Nicole James, PhD
Women & Infants Hospital of Rhode Island
The evaluation of amphiregulin as a novel immunomodulatory high grade serous ovarian cancer therapy
Project Summary
High grade serous ovarian cancer is the most lethal of all gynecologic cancers. While patients typically respond well to chemotherapy, eventually their disease returns, and they become unresponsive to treatment. Therefore, in order to improve patient prognosis, there is an urgent need to better understand factors that influence chemotherapy response and resistance. In recent years, efforts have focused on the development of targeted therapies that function to activate the patient’s immune system to fight tumor cells, called immunotherapies; however ovarian cancer patients have been largely unresponsive to these current treatments. It has been theorized that this lack of response is due to the complex and unique nature of the ovarian tumor microenvironment, a network composed of multiple cell types that surround and influence the tumor. Our groups previous work has identified that the gene amphiregulin is highly overexpressed in patient tumors following chemotherapy exposure and is significantly upregulated in patients that have chemoresistant disease. Therefore, this investigation will examine how amphiregulin affects the ovarian tumor immune microenvironment as well as determine the efficacy of targeting this factor alone and with chemotherapy and immunotherapy. Ultimately, results from this research will generate an unprecedented understanding of the immune-mediated mechanistic and therapeutic effects of amphiregulin in the context of ovarian cancer for the first time.
Bio
Dr. Nicole James is an Assistant Professor (Research) of Obstetrics and Gynecology at the Warren Alpert Medical School of Brown University and Women and Infants Hospital of Rhode Island. She received her BS in Biology from Providence College and obtained her Ph.D. in Pharmaceutical Sciences from the University of Rhode Island. Her postdoctoral fellowship was completed at Women and Infants Hospital of Rhode Island where she was subsequently appointed as research faculty. Since her time as a graduate student Dr. James's research has been primarily focused on ovarian cancer. Her early pre-doctoral work evaluated human epididymis protein 4 (HE4) 's role in ovarian cancer pathogenesis and immune evasion, while her postdoctoral studies focused on translational immune profiling of high grade serous ovarian cancer patient tissue to uncover novel immune prognostic markers indicative of improved outcomes. Dr. James's lab's current research centers upon elucidating the role that amphiregulin (AREG) plays in modulating the ovarian tumor immune microenvironment and targeting AREG in combination with standard of care chemotherapy and clinically available immunotherapies to improve high grade serous ovarian cancer patient clinical outcomes.