Douglas W. DeSimone

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Primary Appointment

Ivy Pratt Distinguished Professor of Morphogenesis, and Chair of Cell Biology, Cell Biology

Education

  • BS, Life Sciences, Worcester Polytechnic Institute
  • PhD, Biology, Dartmouth College
  • Postdoc, Cell and Molecular Biology, Massachusetts Institute of Technology

Research Disciplines

Biotechnology, Cell and Developmental Biology, Computational Biology, Development, Stem Cells & Regeneration, Molecular Biology

Research Interests

Cell Adhesion and Adhesion-Dependent Cell Signaling in Vertebrate Morphogenesis

Research Description

Research in the DeSimone laboratory centers on the problem of morphogenesis, which is the process biological systems use to generate form and develop increasingly complex structures needed to carry out the specialized functions of tissues, organs and whole organisms. We are interested in elucidating how the "linear" information encoded in genomes is played out over time to yield the fantastic variety of 3-dimensional biological form that we associate with all multi-celled organisms. Our specific research focus is the regulation of cell adhesion and adhesion-dependent cell signaling pathways important for directing cell motility and cell polarity in amphibian embryos. One central hypothesis is that the embryonic extracellular matrix (ECM) serves to define compartments within which cell movements are confined and regulated. We have established that integrin-ECM interactions are a necessary component of the cellular machinery regulating collective cell migration and the radial and mediolateral cell-intercalation behaviors that drive midline convergence and axial extension at gastrulation. In recent years our studies have focused increasingly on the signaling crosstalk between cadherin adhesions at cell-cell interfaces and integrin adhesions to the ECM. We have determined that tugging forces on cadherin adhesions are required to establish the polarized protrusions of collectively migrating cells. Current research seeks to elucidate the instructive importance of mechanical signals in directing morphogenetic behaviors of cells and tissues and related mechanisms of adhesion-dependent mechanotransduction. We anticipate that basic knowledge derived from such "simple" model systems of morphogenetic change will be critical to advancing the field of regenerative medicine and the practical applications of tissue engineering.

Training

  • Biotechnology Training Grant

Selected Publications

2023

Comlekoglu, T., Dzamba, B. J., Pacheco, G. G., Shook, D. R., Sego, T. J., Glazier, J. A., . . . DeSimone, D. W. (2023). Modeling the roles of cohesotaxis, cell-intercalation, and tissue geometry in collective cell migration of Xenopus mesendoderm.. bioRxiv. doi:10.1101/2023.10.16.562601

2022

Shook, D. R., Wen, J. W. H., Rolo, A., O'Hanlon, M., Francica, B., Dobbins, D., . . . Keller, R. E. (2022). Characterization of convergent thickening, a major convergence force producing morphogenic movement in amphibians. ELIFE, 11. doi:10.7554/eLife.57642

2021

Watanabe, H., Belyea, B. C., Paxton, R. L., Li, M., Dzamba, B. J., DeSimone, D. W., . . . Sequeira-Lopez, M. L. S. (2021). Renin Cell Baroreceptor, a Nuclear Mechanotransducer Central for Homeostasis. CIRCULATION RESEARCH, 129(2), 262-276. doi:10.1161/CIRCRESAHA.120.318711

2018

Shook, D., Wen, J., Rolo, A., Francica, B., Dobins, D., Skoglund, P., . . . Keller, R. (2018). Characterization of convergent thickening, a major convergence force producing morphogenic movement in amphibians. doi:10.1101/270892

Dzamba, B. J., & DeSimone, D. W. (2018). Extracellular Matrix (ECM) and the Sculpting of Embryonic Tissues. EXTRACELLULAR MATRIX AND EGG COATS, 130, 245-274. doi:10.1016/bs.ctdb.2018.03.006

2017

Sonavane, P. R., Wang, C., Dzamba, B., Weber, G. F., Periasamy, A., & DeSimone, D. W. (2017). Mechanical and signaling roles for keratin intermediate filaments in the assembly and morphogenesis of Xenopus mesendoderm tissue at gastrulation. DEVELOPMENT, 144(23), 4363-4376. doi:10.1242/dev.155200

2014

DeSimone, D. W., & Horwitz, A. R. (2014). Many modes of motility. SCIENCE, 345(6200), 1002-U226. doi:10.1126/science.1259176

Bjerke, M. A., Dzamba, B. J., Wang, C., & Desimone, D. W. (2014). FAK is required for tension-dependent organization of collective cell movements in Xenopus mesendoderm. DEVELOPMENTAL BIOLOGY, 394(2), 340-356. doi:10.1016/j.ydbio.2014.07.023

Rozario, T., Mead, P. E., & DeSimone, D. W. (2014). Diverse functions of kindlin/fermitin proteins during embryonic development in Xenopus laevis. MECHANISMS OF DEVELOPMENT, 133, 203-217. doi:10.1016/j.mod.2014.07.004

2012

Batra, N., Burra, S., Siller-Jackson, A. J., Gu, S., Xia, X., Weber, G. F., . . . Jiang, J. X. (2012). Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109(9), 3359-3364. doi:10.1073/pnas.1115967109

Xu, G., Wei, S., White, J. M., & DeSimone, D. W. (2012). Identification and characterization of ADAM41, a novel ADAM metalloproteinase in Xenopus. INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 56(5), 333-339. doi:10.1387/ijdb.113444gx

2011

Wei, S., Xu, G., Bridges, L. C., Williams, P., Nakayama, T., Shah, A., . . . DeSimone, D. W. (2012). Roles of ADAM13-regulated Wnt activity in early Xenopus eye development. DEVELOPMENTAL BIOLOGY, 363(1), 147-154. doi:10.1016/j.ydbio.2011.12.031

Weber, G. F., Bjerke, M. A., & DeSimone, D. W. (2012). A Mechanoresponsive Cadherin-Keratin Complex Directs Polarized Protrusive Behavior and Collective Cell Migration. DEVELOPMENTAL CELL, 22(1), 104-115. doi:10.1016/j.devcel.2011.10.013

Schwarzbauer, J. E., & DeSimone, D. W. (2011). Fibronectins, Their Fibrillogenesis, and In Vivo Functions. COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 3(7). doi:10.1101/cshperspect.a005041

Weber, G. F., Bjerke, M. A., & DeSimone, D. W. (2011). Integrins and cadherins join forces to form adhesive networks. JOURNAL OF CELL SCIENCE, 124(8), 1183-1193. doi:10.1242/jcs.064618

Weber, G. F., Bjerke, M. A., & DeSimone, D. W. (2011). Integrins and cadherins join forces to form adhesive networks (vol 124, pg 1183, 2011). JOURNAL OF CELL SCIENCE, 124(9), 1601. doi:10.1242/jcs.091074

2010

Wei, S., Xu, G., Bridges, L. C., Williams, P., White, J. M., & DeSimone, D. W. (2010). ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling. DEVELOPMENTAL CELL, 19(2), 345-352. doi:10.1016/j.devcel.2010.07.012

Wei, S., Whittaker, C. A., Xu, G., Bridges, L. C., Shah, A., White, J. M., & DeSimone, D. W. (2010). Conservation and divergence of ADAM family proteins in the Xenopus genome. BMC EVOLUTIONARY BIOLOGY, 10. doi:10.1186/1471-2148-10-211