Daniel P. Kiehart

Professor of Biology

Office: 
4330 French Family Science Cen, Science Drive, Duke University, Durham, NC 27708-0338
Campus Box: 
Box 90338, Dept. Biology, Duke University, Durham, NC 27708-1000
Phone: 
(919) 613-8157
Our intellectual focus is on identifying determinants of cell shape that function during development. Utilizing molecular genetic and reverse genetic approaches in Drosophila, we have shown that conventional nonmuscle myosin is necessary for driving both cell division and post-mitotic cell shape changes for morphogenesis. Currently, we are investigating how myosin elicits cell shape change and how its function is regulated through filament formation, phosphorylation, sub-cellular targeting, small GTP-binding proteins, kinase and phosphatase functions. In fly, we are using novel, near saturating screens to identify mutations that perturb dorsal closure, a model cell sheet movement that requires at least six different filamentous actin and/or actomyosin arrays for proper morphogenesis. Our screens show that nearly all aspects of closure a mutable -- by extrapolating our results, which have thus far screened approximately two-fifths of the fly genome, we project that the function of over 300 genes are required to drive this superficially simple, yet remarkably complex and sophisticated morphogenic process. We have also identified gene products that are necessary for myosin function by genetically recovering second site non-complementing loci and biochemically recovering proteins that bind to myosin. To date, our experiments identify ~30 loci that genetically interact with myosin and a kinase activity that phosphorylates myosin heavy chain and establish genetically, that the Rho signalling pathway is required in concert with nonmuscle myosin II for morphogenesis. Finally, we are using laser microsurgery and micro-manipulation studies to understand the forces that drive  morphogenesis. We show that both the amnioserosa and the leading edge of the lateral epidermis contribute to the movements of dorsal closure. Finally, we are examining the role these proteins play in movements that occur during wound healing.

Education

  • Student, Summer Institute For Scientific Teaching, University of Wisconsin - Madison 2009 - 2009

  • Student, Physiology Course, Marine Biological Laboratory 1985 - 1985

  • Postdoctoral Fellow, Cell Biology And Anatomy, Johns Hopkins University 1978 - 1982

  • Ph.D., University of Pennsylvania 1979

  • B.A., University of Pennsylvania 1973

Sallee, Jennifer L., Janice M. Crawford, Vinay Singh, and Daniel P. Kiehart. “Mutations in Drosophila crinkled/Myosin VIIA disrupt denticle morphogenesis.Developmental Biology 470 (February 2021): 121–35. https://doi.org/10.1016/j.ydbio.2020.11.007. Full Text

Fogerson, Stephanie M., Richard D. Mortensen, Regan P. Moore, Hellen Y. Chiou, Neel K. Prabhu, Angela H. Wei, Daniel Tsai, et al. “Identifying Key Genetic Regions for Cell Sheet Morphogenesis on Chromosome 2L Using a Drosophila Deficiency Screen in Dorsal Closure.G3 (Bethesda, Md.) 10, no. 11 (November 5, 2020): 4249–69. https://doi.org/10.1534/g3.120.401386. Full Text

Kiehart, Daniel P., and John A. Cooper. “Contractile protein biochemistry in the Pollard Lab in Baltimore.Biophysical Reviews 10, no. 6 (December 2018): 1483–85. https://doi.org/10.1007/s12551-018-0477-5. Full Text

Guo, Yuting, Di Li, Siwei Zhang, Yanrui Yang, Jia-Jia Liu, Xinyu Wang, Chong Liu, et al. “Visualizing Intracellular Organelle and Cytoskeletal Interactions at Nanoscale Resolution on Millisecond Timescales.Cell 175, no. 5 (November 2018): 1430-1442.e17. https://doi.org/10.1016/j.cell.2018.09.057. Full Text

Aristotelous, A. C., J. M. Crawford, G. S. Edwards, D. P. Kiehart, and S. Venakides. “Mathematical models of dorsal closure.Progress in Biophysics and Molecular Biology 137 (September 2018): 111–31. https://doi.org/10.1016/j.pbiomolbio.2018.05.009. Full Text

Mortensen, Richard D., Regan P. Moore, Stephanie M. Fogerson, Hellen Y. Chiou, Chimdindu V. Obinero, Neel K. Prabhu, Angela H. Wei, Janice M. Crawford, and Daniel P. Kiehart. “Identifying Genetic Players in Cell Sheet Morphogenesis Using a Drosophila Deficiency Screen for Genes on Chromosome 2R Involved in Dorsal Closure.G3 (Bethesda, Md.) 8, no. 7 (July 2, 2018): 2361–87. https://doi.org/10.1534/g3.118.200233. Full Text

Lo, Wei-Chang, Craig Madrak, Daniel P. Kiehart, and Glenn S. Edwards. “Unified biophysical mechanism for cell-shape oscillations and cell ingression.Physical Review. E 97, no. 6–1 (June 2018): 062414. https://doi.org/10.1103/physreve.97.062414. Full Text

Kiehart, Daniel P., Janice M. Crawford, Andreas Aristotelous, Stephanos Venakides, and Glenn S. Edwards. “Cell Sheet Morphogenesis: Dorsal Closure in Drosophila melanogaster as a Model System.Annual Review of Cell and Developmental Biology 33 (October 2017): 169–202. https://doi.org/10.1146/annurev-cellbio-111315-125357. Full Text

Cao, Jingli, Jinhu Wang, Christopher P. Jackman, Amanda H. Cox, Michael A. Trembley, Joseph J. Balowski, Ben D. Cox, et al. “Tension Creates an Endoreplication Wavefront that Leads Regeneration of Epicardial Tissue.Dev Cell 42, no. 6 (September 25, 2017): 600-615.e4. https://doi.org/10.1016/j.devcel.2017.08.024. Full Text

Lu, Heng, Adam Sokolow, Daniel P. Kiehart, and Glenn S. Edwards. “Quantifying dorsal closure in three dimensions.Molecular Biology of the Cell 27, no. 25 (December 2016): 3948–55. https://doi.org/10.1091/mbc.e16-06-0400. Full Text

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Selected Grants

Genetic and Genomics Training Grant awarded by National Institutes of Health (Mentor). 2020 to 2025

Morphogenesis: Biophysics and Genetics of Dorsal Closure awarded by National Institutes of Health (Principal Investigator). 2018 to 2023

Training Program in Developmental and Stem Cell Biology awarded by National Institutes of Health (Mentor). 2001 to 2022

Faculty Springboard to Advance Breakthrough Science by Post-Tenure Faculty awarded by National Science Foundation (Co-Principal Investigator). 2018 to 2021

Super-resolution Imaging via Multiple Modalities with the Zeiss Elyra 7 awarded by National Institutes of Health (Major User). 2020 to 2021

Genetics Training Grant awarded by National Institutes of Health (Mentor). 1979 to 2020

Organization and Function of Cellular Structure awarded by National Institutes of Health (Mentor). 1975 to 2020

Morphogenesis: Biophysics and Genetics of Dorsal Closure awarded by National Institutes of Health (Principal Investigator). 1984 to 2018

Lightsheet Imaging System awarded by National Institutes of Health (Major User). 2016 to 2017

Structural Biology and Biophysics Training Program awarded by National Institutes of Health (Mentor). 1994 to 2015

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