Dan P. Kiehart

Professor of Biology

Office: 
4330 French Family Science Center, 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, and cellular locomotions. Currently, we are investigating how myosin elicits cell shape change and how its function is regulated through filament formation, phosphorylation, sub-cellular targeting and small GTP-binding protein function. We are characterizing myosin light chain kinase; a novel myosin VII heavy chain; and additional elements that participate in localizing myosin and transmitting the forces that it produces. We used screens for aberrant cell shape induced in the yeast S. pombe by expression of transfected Drosophila cDNAs. These experiments show that elements that define cell shape are conserved throughout phylogeny and that a screen in yeast is a valuable tool for recovering heterologous cDNAs that encode cytoskeletal elements and the proteins that regulate them. In fly, we are identifying 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. We are also using manipulation studies to understand the forces that drive cellularization and 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

  • Ph.D., University of Pennsylvania 1979

  • B.A., University of Pennsylvania 1973

Wells, AR, Zou, RS, Tulu, US, Sokolow, AC, Crawford, JM, Edwards, GS, and Kiehart, DP. "Complete canthi removal reveals that forces from the amnioserosa alone are sufficient to drive dorsal closure in Drosophila." Molecular Biology of the Cell 25, no. 22 (November 2014): 3552-3568. Full Text

Chen, B-C, Legant, WR, Wang, K, Shao, L, Milkie, DE, Davidson, MW, Janetopoulos, C, Wu, XS, Hammer, JA, Liu, Z, English, BP, Mimori-Kiyosue, Y, Romero, DP, Ritter, AT, Lippincott-Schwartz, J, Fritz-Laylin, L, Mullins, RD, Mitchell, DM, Bembenek, JN, Reymann, A-C, Böhme, R, Grill, SW, Wang, JT, Seydoux, G, Tulu, US, Kiehart, DP, and Betzig, E. "Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution." Science (New York, N.Y.) 346, no. 6208 (October 23, 2014): 1257998-null. Full Text

Hunter, GL, Crawford, JM, Genkins, JZ, and Kiehart, DP. "Ion channels contribute to the regulation of cell sheet forces during Drosophila dorsal closure." Development (Cambridge, England) 141, no. 2 (January 2014): 325-334. Full Text

Tulu, US, Beckerle, MC, and Kiehart, DP. "Cell Junctions and the Tension Sensitive, Supracellular Purse Strings in Drosophila Dorsal Closure (Submitted)." J. Cell Biol. (June 2012). (Academic Article)

Hunter, G, Crawford, J, Genkins, J, and Kiehart, DP. "Ion channels function in the mechanoregulation of cell sheet forces during Drosophila morphogenesis (Submitted)." Developmental Cell (May 2012). (Academic Article)

Sokolow, A, Toyama, Y, Kiehart, DP, and Edwards, GS. "Cell ingression and apical shape oscillations during dorsal closure in Drosophila." Biophysical Journal 102, no. 5 (March 6, 2012): 969-979. Full Text

Roh-Johnson, M, Shemer, G, Higgins, CD, McClellan, JH, Werts, AD, Tulu, US, Gao, L, Betzig, E, Kiehart, DP, and Goldstein, B. "Triggering a cell shape change by exploiting preexisting actomyosin contractions." Science (New York, N.Y.) 335, no. 6073 (March 2012): 1232-1235. Full Text

Boyle, MJ, French, RL, Cosand, KA, Dorman, JB, Kiehart, DP, and Berg, CA. "Division of labor: subsets of dorsal-appendage-forming cells control the shape of the entire tube." Dev Biol 346, no. 1 (October 1, 2010): 68-79. Full Text

Franke, JD, Montague, RA, and Kiehart, DP. "Nonmuscle myosin II is required for cell proliferation, cell sheet adhesion and wing hair morphology during wing morphogenesis." Dev Biol 345, no. 2 (September 15, 2010): 117-132. Full Text

Layton, AT, Toyama, Y, Yang, G-Q, Edwards, GS, Kiehart, DP, and Venakides, S. "Drosophila morphogenesis: tissue force laws and the modeling of dorsal closure." HFSP J 3, no. 6 (December 2009): 441-460. Full Text

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Selected Grants

New Console and Cold Probe for the Duke 600 MHz NMR Spectrometer System awarded by National Institutes of Health (Major User). 2013 to 2014

Non Muscle Myosin II Contractility Putatively Regulates Scar Contracture awarded by National Institutes of Health (Co-Mentor). 2008 to 2013

Actin Protrusions, Oocytes: Myosin VIIA and the Actin Cytoskeleton awarded by National Institutes of Health (Principal Investigator). 2010 to 2013

Replacement Equipment Components for an 800 MHz NMR Spectrometer awarded by National Institutes of Health (Major User). 2010 to 2011

Myosins VIIA, VIIB & XV in Fly Hearing and Morphogenesis awarded by National Institutes of Health (Principal Investigator). 2005 to 2011

Integrated instrument systems for maintenance and delivery of RNAi libraries awarded by National Institutes of Health (Co Investigator). 2008 to 2009

Duke PREP: Minority Recruitment into Biomedical Sciences awarded by National Institutes of Health (Advisor). 2003 to 2008

Molecular Genetic Analysis of Wound Healing in Drosophila awarded by National Institutes of Health (Principal Investigator). 2000 to 2004

Cytoplasmic Myosin Function in Vivo and in Vitro awarded by National Institutes of Health (Principal Investigator). 1984 to 2004

Center for FEL Research in the Medical, Biological, and Materials Sciences awarded by Air Force Office of Scientific Research (Co-Principal Investigator). 2000 to 2001

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