Research Summary

Multicellular organisms possess a remarkable capacity for the development, maintenance, and regeneration of robust tissue patterns, even while facing considerable environmental and genetic challenges. Regulation of tissue patterns and the individual cell states they comprise is critical during embryonic development; failures can lead to birth defects, developmental disorders, and/or lethality. While we currently understand many of the links connecting environmental and genetic perturbations to their ultimate effects on embryos, a significant proportion of human pregnancies still result in developmental defects or miscarriages of unknown cause. At present, we also often fail to understand why certain genetic or environmental perturbations result in failed embryogenesis in some individuals, but not in others. Feedback regulation of cell fate decisions within tissues is one strategy by which developing embryos buffer a wide range of perturbations to achieve healthy outcomes. My research seeks to understand feedback mechanisms that underlie cell fate and tissue pattern robustness, as well as the disease states that arise when these mechanisms fail. My lab studies these mechanisms in the zebrafish (Danio rerio), a vertebrate species whose embryos bear considerable genetic and anatomical similarity to those of humans. As a model system, zebrafish embryos can be studied with a wide variety of reverse genetic, lineage-tracing, imaging, and molecular tools. My lab will additionally leverage single-cell genomics methods, including TRACERSEQ and STITCH, which I developed in my postdoc, to map quantitative relationships between cell lineage and cell state, in both healthy and perturbed contexts. Such analyses will also reveal transcriptional signatures for how all tissues of a developing embryo respond to perturbations, yielding candidate genes for targeted in vivo developmental genetic studies. We will additionally use comparative approaches to relate molecular details of feedback mechanisms discovered in zebrafish to their counterparts in humans.

Research Funding

  • March 1, 2022 - March 1, 2027 - Challenging and decoding the logic of cell fate feedback control in the developing zebrafish embryo , Principal Investigator . Sponsor: Chan Zuckerberg Biohub, Sponsor Award ID: 7031078
  • September 23, 2021 - August 31, 2024 - Mapping cell fate flow and feedback control on vertebrate embryonic landscapes , Principal Investigator . Sponsor: NIH, Sponsor Award ID: DP2GM146258
  • July 1, 2021 - June 30, 2024 - Elucidating molecular mechanisms of pattern repair in zebrafish embryos , Principal Investigator . Sponsor: Searle Scholar's Program, Kinship Foundation, Sponsor Award ID: 136867A
  • June 1, 2020 - May 31, 2023 - Mapping vertebrate differentiation hierarchies with high-throughput single cell transcriptomics , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R00GM121852


Postdoc, 2019 - Systems Biology, Harvard Medical School
Ph.D, 2012 - Biology, MIT
B.S., 2003 - Biology, Chemistry, Haverford College

Honors & Awards

  • Biohub Investigator, Chan Zuckerberg Biohub, 2022-2027
  • NIH Director's New Innovator Award, NIH/NIGMS, 2021-2026
  • Searle Scholar, Kinship Foundation, 2021-2024
  • 2018 Breakthrough of the Year - "Development Cell by Cell", Science Magazine, 2018
  • K99/R00 Pathway to Independence Award, NIH/NIGMS, 2017-2023
  • HHMI Postdoctoral Fellowship of the Life Sciences Research Foundation (LSRF), HHMI/LSRF, 2015-2017
  • Praecis Presidential Graduate Fellowship, MIT, 2005-2006
  • Ariel G. Lowy Prize for Biology Research, Haverford College, 2003
  • Howard Hughes Medical Institute Interdisciplinary Scholar, Haverford College, 2002

Selected Publications

  1. Graded BMP signaling within intestinal crypt architecture directs self-organization of the Wnt-secreting stem cell niche. Cell Stem Cell. 2023; 4(30):433-449.  View on PubMed
  2. Kraiczy J, McCarthy N, Malagola E, Tie G, Madha S, Boffelli D, Wagner DE, Wang TC, Shivdasani RA. Graded BMP signaling within intestinal crypt architecture directs self-organization of the Wnt-secreting stem cell niche. Cell Stem Cell. 2023 04 06; 30(4):433-449.e8.  View on PubMed
  3. Wagner DE. Triangulating spatial relationships from single-cell interaction maps. Nat Methods. 2021 08; 18(8):867-869.  View on PubMed
  4. Wagner DE, Klein AM. Lineage tracing meets single-cell omics: opportunities and challenges. Nat Rev Genet. 2020 07; 21(7):410-427.  View on PubMed
  5. Diaz-Cuadros M, Wagner DE, Budjan C, Hubaud A, Tarazona OA, Donelly S, Michaut A, Al Tanoury Z, Yoshioka-Kobayashi K, Niino Y, Kageyama R, Miyawaki A, Touboul J, Pourquié O. In vitro characterization of the human segmentation clock. Nature. 2020 04; 580(7801):113-118.  View on PubMed
  6. Sharma N, Flaherty K, Lezgiyeva K, Wagner DE, Klein AM, Ginty DD. The emergence of transcriptional identity in somatosensory neurons. Nature. 2020 01; 577(7790):392-398.  View on PubMed
  7. Tewari AG, Owen JH, Petersen CP, Wagner DE, Reddien PW. A small set of conserved genes, including sp5 and Hox, are activated by Wnt signaling in the posterior of planarians and acoels. PLoS Genet. 2019 10; 15(10):e1008401.  View on PubMed
  8. Wagner DE, Weinreb C, Collins ZM, Briggs JA, Megason SG, Klein AM. Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo. Science. 2018 06 01; 360(6392):981-987.  View on PubMed
  9. Briggs JA, Weinreb C, Wagner DE, Megason S, Peshkin L, Kirschner MW, Klein AM. The dynamics of gene expression in vertebrate embryogenesis at single-cell resolution. Science. 2018 06 01; 360(6392).  View on PubMed
  10. Raj B, Wagner DE, 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. Nat Biotechnol. 2018 06; 36(5):442-450.  View on PubMed
  11. Wang IE, Wagner DE, Reddien PW. Clonal Analysis of Planarian Stem Cells by Subtotal Irradiation and Single-Cell Transplantation. Methods Mol Biol. 2018; 1774:479-495.  View on PubMed
  12. Wagner DE, Klein AM. Genetic screening enters the single-cell era. Nat Methods. 2017 02 28; 14(3):237-238.  View on PubMed
  13. Owen JH, Wagner DE, Chen CC, Petersen CP, Reddien PW. teashirt is required for head-versus-tail regeneration polarity in planarians. Development. 2015 Mar 15; 142(6):1062-72.  View on PubMed
  14. van Wolfswinkel JC, Wagner DE, Reddien PW. Single-cell analysis reveals functionally distinct classes within the planarian stem cell compartment. Cell Stem Cell. 2014 Sep 04; 15(3):326-339.  View on PubMed
  15. Witchley JN, Mayer M, Wagner DE, Owen JH, Reddien PW. Muscle cells provide instructions for planarian regeneration. Cell Rep. 2013 Aug 29; 4(4):633-41.  View on PubMed
  16. Wagner DE, Ho JJ, Reddien PW. Genetic regulators of a pluripotent adult stem cell system in planarians identified by RNAi and clonal analysis. Cell Stem Cell. 2012 Mar 02; 10(3):299-311.  View on PubMed
  17. Wagner DE, Wang IE, Reddien PW. Clonogenic neoblasts are pluripotent adult stem cells that underlie planarian regeneration. Science. 2011 May 13; 332(6031):811-6.  View on PubMed
  18. Wagner DE, Phillips CL, Ali WM, Nybakken GE, Crawford ED, Schwab AD, Smith WF, Fairman R. Toward the development of peptide nanofilaments and nanoropes as smart materials. Proc Natl Acad Sci U S A. 2005 Sep 06; 102(36):12656-61.  View on PubMed

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