Dan Wagner, PhD
Assistant Professor
Ob/Gyn, Reproductive Sciences
School of Medicine
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.
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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.
Awards
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- 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
Education & Training
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- Postdoc Systems Biology Harvard Medical School 2019
- Ph.D Biology MIT 2012
- B.S. Biology, Chemistry Haverford College 2003
Interests
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- Zebrafish
- Bioinformatics
- Lineage
- Single-cell 'omics
Websites
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- @@danwagnerlab on Twitter (twitter.com)
- Wagner Lab Website (danwagnerlab.org)
Grants and Projects
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- Challenging and decoding the logic of cell fate feedback control in the developing zebrafish embryo, Chan Zuckerberg Biohub, 2022-2027
- Mapping cell fate flow and feedback control on vertebrate embryonic landscapes, NIH, 2021-2024
- Elucidating molecular mechanisms of pattern repair in zebrafish embryos, Searle Scholar's Program, Kinship Foundation, 2021-2024
- Mapping vertebrate differentiation hierarchies with high-throughput single cell transcriptomics, NIH, 2020-2023
- Mapping vertebrate differentiation hierarchies with high-throughput single cell transcriptomics, NIH, 2017-2019
Publications (19)
Top publication keywords:
Zebrafish ProteinsPluripotent Stem CellsAdult Stem CellsGenomicsEsophageal NeoplasmsGene Expression Regulation, DevelopmentalEmbryonic DevelopmentRNA InterferencePlanariansCell LineageGenetic TestingZebrafishRegenerationClonal EvolutionSingle-Cell Analysis
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Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo.
Science (New York, N.Y.) 2018 Wagner DE, Weinreb C, Collins ZM, Briggs JA, Megason SG, Klein AM -
The dynamics of gene expression in vertebrate embryogenesis at single-cell resolution.
Science (New York, N.Y.) 2018 Briggs JA, Weinreb C, Wagner DE, Megason S, Peshkin L, Kirschner MW, Klein AM -
Simultaneous single-cell profiling of lineages and cell types in the vertebrate brain.
Nature biotechnology 2018 Raj B, Wagner DE, McKenna A, Pandey S, Klein AM, Shendure J, Gagnon JA, Schier AF -
Clonogenic neoblasts are pluripotent adult stem cells that underlie planarian regeneration.
Science (New York, N.Y.) 2011 Wagner DE, Wang IE, Reddien PW -
Pluripotency of a founding field: rebranding developmental biology.
Development (Cambridge, England) 2024 Rogers CD, Amemiya C, Arur S, Babonis L, Barresi M, Bartlett M, Behringer R, Benham-Pyle B, Bergmann D, Blackman B, Brown CT, Browne B, Camacho J, Chabu CY, Chow I, Cleaver O, Cool J, Dennis MY, …
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Graded BMP signaling within intestinal crypt architecture directs self-organization of the Wnt-secreting stem cell niche
Cell Stem Cell 2023 -
Graded BMP signaling within intestinal crypt architecture directs self-organization of the Wnt-secreting stem cell niche.
Cell stem cell 2023 Kraiczy J, McCarthy N, Malagola E, Tie G, Madha S, Boffelli D, Wagner DE, Wang TC, Shivdasani RA -
Triangulating spatial relationships from single-cell interaction maps.
Nature methods 2021 Wagner DE -
Lineage tracing meets single-cell omics: opportunities and challenges.
Nature reviews. Genetics 2020 Wagner DE, Klein AM -
In vitro characterization of the human segmentation clock.
Nature 2020 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 -
The emergence of transcriptional identity in somatosensory neurons.
Nature 2020 Sharma N, Flaherty K, Lezgiyeva K, Wagner DE, Klein AM, Ginty DD -
A small set of conserved genes, including sp5 and Hox, are activated by Wnt signaling in the posterior of planarians and acoels.
PLoS genetics 2019 Tewari AG, Owen JH, Petersen CP, Wagner DE, Reddien PW -
Clonal Analysis of Planarian Stem Cells by Subtotal Irradiation and Single-Cell Transplantation.
Methods in molecular biology (Clifton, N.J.) 2018 Wang IE, Wagner DE, Reddien PW -
Genetic screening enters the single-cell era.
Nature methods 2017 Wagner DE, Klein AM -
teashirt is required for head-versus-tail regeneration polarity in planarians.
Development (Cambridge, England) 2015 Owen JH, Wagner DE, Chen CC, Petersen CP, Reddien PW -
Single-cell analysis reveals functionally distinct classes within the planarian stem cell compartment.
Cell stem cell 2014 van Wolfswinkel JC, Wagner DE, Reddien PW -
Muscle cells provide instructions for planarian regeneration.
Cell reports 2013 Witchley JN, Mayer M, Wagner DE, Owen JH, Reddien PW -
Genetic regulators of a pluripotent adult stem cell system in planarians identified by RNAi and clonal analysis.
Cell stem cell 2012 Wagner DE, Ho JJ, Reddien PW -
Toward the development of peptide nanofilaments and nanoropes as smart materials.
Proceedings of the National Academy of Sciences of the United States of America 2005 Wagner DE, Phillips CL, Ali WM, Nybakken GE, Crawford ED, Schwab AD, Smith WF, Fairman R