If ovarian cancer takes decades to develop, why are we still unable to detect the disease at an early stage when surgery is curative? Only recently have scientist demonstrated that many of the most common and deadly ovarian cancers actually do not originate in the ovary, but in the fallopian tube. This realization necessitates changes in identifying the underlying cause of the disease in order to exploit and expand new diagnostic tools focused on early precursor lesion confined to the fallopian tubes. Developing non-invasive and highly specific blood-based tests, i.e., “liquid biopsies” for pre-symptomatic screening and early detection of ovarian cancer is, therefore, the holy grail. We will focus our program project grant supported by the OCRA to study tiny vesicles (membrane-bound sacs) found circulating in blood at high concentrations (>1 billion particles in a teaspoon of blood) that are a 1000-times smaller than the width of an average human hair. These nanosized vesicles, referred to as exosomes, are released by all types of cells in the body, both healthy and tumor cells: in the disease state the number of exosomes in blood are greatly elevated. Longitudinal studies connecting early fallopian tube proteins that correlate with disease progression in the blood are a challenge due to the length of time for disease to develop and the incidence of ovarian cancer. Therefore, model systems are a critical tool to predict changes that will persist over the course of disease in order to find successful biomarkers. In studies led by Dr. Joanna Burdette (University of Illinois at Chicago), we will determine how ovarian exosomes can modify the cells in the fallopian tube and turn on signals that convert normal cells into preneoplastic lesions. In complementary studies led by Dr. Andrew K. Godwin (University of Kansas Medical Center), we will exploit a specific subset of these exosomes as robust indicators or “biomarkers” to detect the early presence of the deadliest forms of ovarian cancer before it leaves the fallopian tubes for “greener pastures”. Both projects leverage novel microfluidics. Dr. Godwin’s project uses “lab-on-a-chip” technologies which can specifically capture and analyze ovarian exosomes that accumulate in bodily fluids of women at increased risk. Although small, these mighty vesicles are chocked full of biomarkers, which can be early indicators for the presence of cancer (high sensitivity) and with great certainty of the type of cancer (high specificity). Dr. Burdette’s project uses “organ-on-a-chip” microfluidics to support the growth of normal and preneoplastic lesions of the fallopian tube in order to capture and follow exosomes over disease progression. Thus, this proposal will expand our knowledge of the causes of cancer initiation in the fallopian tubes and then exploit this to measure specific elements of the molecular cargo of ovarian cancer-associated exosomes in blood. These studies will expand our knowledge of the disease and develop innovative molecular tools to better detect ovarian cancer at earlier stages when therapies are curative.
Dr. Andrew K. Godwin is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor and the Director of Molecular Oncology in the Department of Pathology and Laboratory Medicine at the University of Kansas Medical Center. In the latter position, he is the founding director of the Clinical Molecular Oncology Laboratory, a CLIA-certified, CAP-accredited molecular diagnostics laboratory, and heads the institutional efforts in the area of precision medicine. He was recently awarded a COBRE grant from the NIGMS to develop the Kansas Institute for Precision Medicine. Dr. Godwin earned his BS in Cellular Biology from the University of Kansas and his PhD in Molecular Biology from the University of Pennsylvania while carrying out his thesis research at Fox Chase Cancer Center (FCCC) in Philadelphia. During his 26 fruitful years at FCCC, he climbed the ranks from graduate student to Senior Member (full Professor with tenure). In late 2010, Dr. Godwin was recruited to the KU Medical Center as the KU Cancer Center’s Associate Director for Translational Research and his engaged participation contributed towards NCI designation in 2012, resulted in him being named the Deputy Director in 2013. Dr. Godwin also serves as the Director of the KUMC’s Biospecimen Repository Core Facility (BRCF) as well as the Scientific Director for the Biomarker Discovery Laboratory (BDL). He also leads the ovarian cancer research-working group at KUMC and is a member of the Investigator Initiated Trial Steering Committee. He was named a Kansas Bioscience Authority Eminent Scholar in 2010 and his contributions towards education and training was recognized when he was presented the KUMC School of Medicine Achievement Award for Mentoring Post-Docs in 2014, the KU Medical Center’s Faculty Investigator Research Award in 2015, the University of Kansas Cancer Center Director’s William Jewell Team Science Award in 2017, the KUCC Director’s Basic Science Award in 2018 and most recently the prestigious 2018 Chancellor’s Club Award.
Dr. Godwin is a leader in the field of translational research and precision medicine, and his laboratories at KUMC continue to focus on various aspects of both basic and translational research, with an emphasis on early detection of cancer, predictive and prognostic biomarkers, liquid biopsies based on extracellular vesicles, molecular therapeutics, companion diagnostics, clinical trials, and biosample ascertainment. He is internationally recognized for his molecular biology/genetic studies of sarcoma (e.g., GIST and Ewing Sarcoma), breast and ovarian cancer, and his efforts to help bridge the gap between basic and clinical science in order to improve patient care. Dr. Godwin has been the Translational Science Co-chair for many Gynecologic Oncology Group (GOG, now a part of the NRG) clinical trials evaluating molecularly targeted agents in recurrent ovarian and endometrial cancer patients. He is a currently a member of the Early Therapeutics and Rare Cancers Committee and the Vice Chair of the Breast Translational Medicine subcommittee of the Southwest Oncology Group (SWOG) and remains active in ovarian cancer advocacy.