Melissa Harrison

Research Description:

Research in the Harrison lab focuses on how information encoded in the genome is differentially interpreted during organismal development. Specifically, we study the molecular mechanisms regulating gene expression and how changes in gene expression drive cell identity. We leverage the wide number of tools available in Drosophila to study conserved developmental transitions, enabling us to uncover fundamental principles governing cell-fate specification. Current research in the lab is primarily directed at understanding the function of proteins that act at the top of gene regulatory networks to elicit dramatic changes in cell fate.

Among the conserved developmental transitions studied in the lab are the molecular mechanisms that allow the genomes of the sperm and egg to be remodeled following fertilization, creating the totipotent state. This reprogramming requires the activity of specialized transcription factors, termed pioneer factors, that can uniquely access the genome within the context of chromatin and define regions that will be subsequently bound by additional transcription factor. Pioneer factors also function at the top of gene regulatory networks during additional developmental transitions. The Harrison lab studies multiple pioneer factors that function in diverse cellular contexts to define cell fate. In addition to the early embryo, we investigate how pioneer factors promote neural stem cell pluripotency and what limits their ability to interact with chromatin. Additional work in the lab, builds on the high conservation between humans and flies to model human diseases, including cancer.

Representative Publications:
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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 doi.org/10.1016/j.devcel.2023.06.010

Harrison, M.M., Marsh, A.J., and C.A. Rushlow. (2023) Setting the stage for development: the maternal-to-zygotic transition in Drosophila. Genetics in press

Larson, E.D., Komori, H., Gibson, T.J., Ostgaard, C.M., Hamm, D.C., Schnell, J.M., Lee, C-Y, and Harrison, M. M. (2021) Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila. Nat Comm. doi.org/10.1038/s41467-021-27506-y

Gaskill, M.M., Gibson, T.J., Larson, E.D. and Harrison, M.M. (2021) GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo. eLife doi.org/10.7554/eLife.66668

Larson, E.D., Marsh, A.J., and Harrison, M. M. (2021) Pioneering the developmental frontier. Mol Cell 81:1640-1650.

Jain, S.U., Rashoff, A.Q., Krabbenhoft, S.D., Hoelper, D., Do, T.J., Gibson, T.J., Lundgren, S.M., Bondra, E.R., Deshmukh, S., Harutyunyan, A.S., Juretic, N., Jabado, N., Harrison, M.M., Lewis, P.W. (2020) H3 K27M and EZHIP Impede H3K27-Methylation Spreading by Inhibiting Allosterically Stimulated PRC2. Mol Cell. 80:726-735.

McDaniel, S.L., Hollatz, A.J., Branstad, A.M., Gaskill, M.M., Fox, C.A., and Harrison, M.M. (2020). Tissue-Specific DNA Replication Defects in Drosophila melanogaster Caused by a Meier-Gorlin Syndrom Mutation in Orc4. Genetics. 214:355-367.

McDaniel, S.M., Gibson, T.J., Schulz, K.N., Fernandez Garcia, M., Nevil, M., Jain, S.U., Lewis, P.W., Zaret, K.S., and Harrison, M.M. (2019). Continued activity of the pioneer factor Zelda is required to drive zygotic genome activation. Mol Cell 74:185-195.