Our lab studies vertebrate development and adult tissue homeostasis through the lens of the lineage tree. The lineage tree is the branching structure of cell divisions that describes relationships between all cells in the adult animal, and connects these cells to their ancestor cells in the embryo. We have developed tools using CRISPR genome editing and single-cell RNA sequencing to record lineage trees with unprecedented scale and granularity.
Our lab studies variability in the vertebrate lineage tree - how it is compensated for and how it can lead to individuality. We are interested in cell signaling pathways, and how they influence cell fate choice at critical branch points within the tree. Finally, our lab researches how stem cells contribute to tissue maintenance and regeneration, particularly in the brain and in the germ line, as animals grow and age. Our lab addresses these topics using genome engineering, sequencing and synthetic biology in the zebrafish, a great model of vertebrate biology.
We also have a variety of side projects driven by curiosity! Approaching classic mysteries of biology with new ideas and methods is our specialty. If you are curious about the intersection of biology, engineering and math, let’s talk.
References (Selected Publications)
- Takasugi PR, Drage EP, Kanishka SN, Higbee MA, Gagnon JA. Orthogonal CRISPR-Cas genome editing and efficient inhibition with anti-CRISPRs in zebrafish embryos. BioRxiv 2020 (Preprint available on https://www.biorxiv.org/content/10.1101/2020.11.07.372151v1)
- Balla KM, Rice MC, Gagnon JA, Elde NC. Linking virus discovery to immune responses visualized during zebrafish infections. Current Biology 2020 30:2092-2103.
- McKenna A, Gagnon JA. Recording development with single cell dynamic lineage tracing. Development 2019 146:dev169730 PMID: 31249005
- Raj B, Wagner DW, McKenna A, Pandey S, Klein AM, Shendure J, Gagnon JA*, Schier AF*. Simultaneous single-cell profiling of lineages and cell types in the vertebrate brain. Nature Biotechnology 2018 36:442-450 PMID: 29608178
- Gagnon JA, Obbad K, Schier AF. The primary role of zebrafish nanog is in extra-embryonic tissue. Development 2018 145:dev147793 PMID: 29180571
- McKenna A*, Findlay G*, Gagnon JA*, Horwitz M, Schier AF, Shendure J. Whole organism lineage tracing by combinatorial and cumulative genome editing. Science 2016 353:aaf7907 PMID: 27229144
- Gagnon JA, Valen E, Thyme SB, Huang P, Akhmetova L, Pauli A, Montague TG, Zimmerman S, Richter C, Schier AF. Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs.PLoS One 2014 9:e98186 PMID: 24873830
- * Equal contribution