Grant: CIHR Fellowship

The billions of cells in your body generally all share the same DNA sequence, and yet they display a vast array of morphologies and functions. Understanding how the same genetic material is interpreted in diverse cell types remains a challenge in modern biology. Diverse processes in a cell drive these heritable changes that do not involve alternations to the genome sequence (epigenetic modifications). There is significant therapeutic potential in improving our understanding of this epigenetic code and in discovering pharmaceuticals capable of altering a cell's epigenetic state. Promising applications include disrupting abnormal cell divisions in cancer or promoting self-renewal in stem cells for clinical use in regenerative medicine. This proposal focuses on the genome-wide characterization of epigenetic changes in stem cells. Stem cells offer a powerful model of the earliest cell commitments to either self-renewal, producing identical daughter cells, or to differentiation into specialized cell types. I will use next-generation sequencing technologies to examine histone modifications, DNA methylation and gene expression patterns in normal stem cells before and after differentiation. In addition, I plan to profile the epigenetic modifications in chemically induced stem cells to compare the patterns to those of normal self-renewing cells. My research will tackle the challenges of computationally distilling biologically meaningful patterns and displaying them in intuitive interfaces that serve to accelerate the transition from raw data to discovery within the health sciences. Using these datasets and the tools I develop, I plan to address questions relating to whether a characteristic epigenetic pattern exists for self-renewing cells. Such an approach will be valuable in evaluating the extent to which chemically induced cells have been reprogrammed and are appropriate for therapeutic use.