2020 Collaborative Research Development Grant Recipient — Andrew K. Godwin, PhD
Project Summary
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.