Melissa Harrison, PhD

Harrison Lab

Research Description

Pluripotent cells have the ability to become virtually any cell type, and the power to control this capacity could revolutionize both basic research and medicine. Advances in reprogramming of specified cell types back to a pluripotent state have generated enthusiasm for the potential to create and manipulate specific cell lineages in culture. While reprogramming has exciting possibilities, the process is inefficient, limiting the future therapeutic benefits. By contrast, reprogramming occurs rapidly and efficiently in the early embryo when fertilized eggs are remodeled to become the embryonic cells that will eventually generate the adult organism. Our group is focused on understanding the fundamental molecular mechanisms by which the embryonic genome is rapidly remodeled to create the pluripotent state. We have shown that this process relies on transcription factors with unique properties that allow them to define regulatory regions. Ongoing studies focus on the unique set of factors that can drive this reprogramming within the context of a developing metazoan and understanding how these proteins shape the genome to affect the dramatic changes in cell fate required for organismal development.

Selected References:

1. Larson, E.D., Komori, H., Gibson, T.J., Ostgaard, C.M., Hamm, D.C., Schnell, J.M., Lee, C.Y., and M.M. Harrison. (2021) Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila. Nat Comm. 12: 7153
2. Gaskill, M.M., Gibson, T.J., Larson, E.D., and M.M. Harrison. (2021) GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo. eLife 10: e66668 doi.org/10.7554/eLife.66668
3. Larson, E.D., Marsh, A.J., and M.M. Harrison. (2021) Pioneering the developmental frontier. Mol Cell 81: 1640-1650.
4. McDaniel, S.L., Gibson, T.J., Schulz, K.N., Fernandez Garcia, M., Nevil, M.N., Jain, S.U., Lewis, P.W., Zaret, K.S., and M.M. Harrison. (2019) Continued activity of the pioneer factor Zelda is required to drive zygotic genome activation. Mol Cell. 74:185-195.