Ovarian cancer remains a disease with high mortality due to late-stage diagnoses and tumor recurrence. Understanding how ovarian tumors begin and come back (recur) would provide new ways to develop early detection methods and targets of recurrent disease. One hypothesis as to how ovarian tumors are initiated and recur is through a rare population of cells called Ovarian Cancer Stem-like Cells (OCSCs). OCSCs have similar characteristics as normal stem cells that can give rise to many kinds of cells in a tissue, but instead possess the ability to produce the cells that comprise ovarian tumors. Further, these cells have been shown to be capable of tumor initiation and possess characteristics that allow them a measure of innate therapy resistance, providing a possible mechanism for tumor re-initiation/recurrence. In this project, we propose to profile individual OCSCs using new technologies we have developed in our group to provide a rich picture of these cells at each step in the process of differentiating into the various types of cells in a tumor in a process known as lineage tracing. The first innovative way we are tackling this problem is by giving each individual OCSC a unique cell barcode. When an OCSC divides into two cells, we will be able to keep track of both the new cell and which cell it came from by sequencing the DNA and RNA. We have developed new sequencing approaches that profile patterns of marks on the DNA (methylation) and how they can regulate which genes are turned on and off (RNA) in the cell. How and why these patterns change during OCSC differentiation will provide new information that we can use to target the tumor initiating cells and potentially lowering disease recurrence, hopefully leading to better patient outcomes.
This grant was made possible in part by a generous donation from The Mike & Patti Hennessy Foundation