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. Freund, M.M., Harrison, M.M. and E.F. Torres-Zelada. (2024) Exploring the reciprocity between pioneer factors and development. Development 151:dev201921.
2. Gibson, T.J., Larson, E.D. and M.M. Harrison. (2024) Protein-intrinsic properties and context-dependent effects regulate pioneer-factor binding and function. Nat Struct Mol Biol 31:548-558.
3. Gaskill, M.M., Soluri, I.V., Branks, A.E., Boka, A.P, Stadler, M.R., Vietor, K., Huang, HY, Gibson, T.J., Mir, M., Blythe, S.A., and M.M. Harrison. (2023) Localization of the pioneer factor GAF to subnuclear foci is driven by DNA binding and required to silence satellite repeat expression. Dev Cell 58: 1610-1624.
4. 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.