Douglas W. DeSimone

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Primary Appointment

Professor and Chair, 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, Development, Stem Cells & Regeneration

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

Dzamba BJ, DeSimone DW, Extracellular Matrix (ECM) and the Sculpting of Embryonic Tissues., 2018; Current topics in developmental biology. 130() 245-274. PMID: 29853179

Sonavane PoojaR., Wang Chong, Dzamba Bette, Weber GregoryF., Periasamy Ammasi, DeSimone DouglasW., Mechanical and signaling roles for keratin intermediate filaments in the assembly and morphogenesis of mesendoderm tissue at gastrulation, 2017; Development. 144() 4363-4376. PMID: | PMCID: PMC5769636

Rozario T, Mead PE, DeSimone DW, Diverse functions of kindlin/fermitin proteins during embryonic development in Xenopus laevis., 2014; Mechanisms of development. 133() 203-17. PMID: 25173804

Bjerke MA, Dzamba BJ, Wang C, DeSimone DW, FAK is required for tension-dependent organization of collective cell movements in Xenopus mesendoderm., 2014; Developmental biology. 394(2) 340-56. PMID: 25127991 | PMCID: PMC4172504

DeSimone DW, Horwitz AR, Cell Biology. Many modes of motility., 2014; Science (New York, N.Y.). 345(6200) 1002-3. PMID: 25170137

Batra N, Burra S, Siller-Jackson AJ, Gu S, Xia X, Weber GF, DeSimone D, Bonewald LF, Lafer EM, Sprague E, Schwartz MA, Jiang JX, Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels., 2012; Proceedings of the National Academy of Sciences of the United States of America. 109(9) 3359-64. PMID: 22331870 | PMCID: PMC3295295

Xu G, Wei S, White JM, DeSimone DW, Identification and characterization of ADAM41, a novel ADAM metalloproteinase in Xenopus., 2012; The International journal of developmental biology. 56(5) 333-9. PMID: 22811267 | PMCID: PMC3695402

Wei S, Xu G, Bridges LC, Williams P, Nakayama T, Shah A, Grainger RM, White JM, DeSimone DW, Roles of ADAM13-regulated Wnt activity in early Xenopus eye development., 2012; Developmental biology. 363(1) 147-54. PMID: 22227340 | PMCID: PMC3288294

Schwarzbauer JE, DeSimone DW, Fibronectins, their fibrillogenesis, and in vivo functions., 2011; Cold Spring Harbor perspectives in biology. 3(7) . PMID: 21576254 | PMCID: PMC3119908

Weber GF, Bjerke MA, DeSimone DW, A mechanoresponsive cadherin-keratin complex directs polarized protrusive behavior and collective cell migration., 2011; Developmental cell. 22(1) 104-15. PMID: 22169071 | PMCID: PMC3264825

Weber GF, Bjerke MA, DeSimone DW, Integrins and cadherins join forces to form adhesive networks., 2011; Journal of cell science. 124(0) 1183-93. PMID: 21444749 | PMCID: PMC3115772

Wei S, Whittaker CA, Xu G, Bridges LC, Shah A, White JM, Desimone DW, Conservation and divergence of ADAM family proteins in the Xenopus genome., 2010; BMC evolutionary biology. 10() 211. PMID: 20630080 | PMCID: PMC3055250

Wei S, Xu G, Bridges LC, Williams P, White JM, DeSimone DW, ADAM13 induces cranial neural crest by cleaving class B Ephrins and regulating Wnt signaling., 2010; Developmental cell. 19(2) 345-52. PMID: 20708595 | PMCID: PMC2951023

Dzamba BJ, Jakab KR, Marsden M, Schwartz MA, DeSimone DW, Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization., 2009; Developmental cell. 16(3) 421-32. PMID: 19289087 | PMCID: PMC2682918

Rozario T, Dzamba B, Weber GF, Davidson LA, DeSimone DW, The physical state of fibronectin matrix differentially regulates morphogenetic movements in vivo., 2009; Developmental biology. 327(2) 386-98. PMID: 19138684 | PMCID: PMC2829434

Rozario T, DeSimone DW, The extracellular matrix in development and morphogenesis: a dynamic view., 2009; Developmental biology. 341(1) 126-40. PMID: 19854168 | PMCID: PMC2854274

Thorne BC, Bailey AM, DeSimone DW, Peirce SM, Agent-based modeling of multicell morphogenic processes during development., 2008; Birth defects research. Part C, Embryo today : reviews. 81(4) 344-53. PMID: 18228259

Schwartz MA, DeSimone DW, Cell adhesion receptors in mechanotransduction., 2008; Current opinion in cell biology. 20(5) 551-6. PMID: 18583124 | PMCID: PMC2581799

Davidson LA, Dzamba BD, Keller R, Desimone DW, Live imaging of cell protrusive activity, and extracellular matrix assembly and remodeling during morphogenesis in the frog, Xenopus laevis., 2008; Developmental dynamics : an official publication of the American Association of Anatomists. 237(10) 2684-92. PMID: 18629871 | PMCID: PMC2628587

DeSimone DW, Dzamba B, Davidson LA, Using Xenopus embryos to investigate integrin function., 2007; Methods in enzymology. 426() 403-14. PMID: 17697893

Robertson SH, Smith CK, Langhans AL, McLinden SE, Oberhardt MA, Jakab KR, Dzamba B, DeSimone DW, Papin JA, Peirce SM, Multiscale computational analysis of Xenopus laevis morphogenesis reveals key insights of systems-level behavior., 2007; BMC systems biology. 1() 46. PMID: 17953751 | PMCID: PMC2190763

Davidson LA, Marsden M, Keller R, Desimone DW, Integrin alpha5beta1 and fibronectin regulate polarized cell protrusions required for Xenopus convergence and extension., 2006; Current biology : CB. 16(9) 833-44. PMID: 16682346

Alfandari D, Cousin H, Gaultier A, Hoffstrom BG, DeSimone DW, Integrin alpha5beta1 supports the migration of Xenopus cranial neural crest on fibronectin., 2003; Developmental biology. 260(2) 449-64. PMID: 12921745

Na J, Marsden M, DeSimone DW, Differential regulation of cell adhesive functions by integrin alpha subunit cytoplasmic tails in vivo., 2003; Journal of cell science. 116(0) 2333-43. PMID: 12711704

Marsden M, DeSimone DW, Integrin-ECM interactions regulate cadherin-dependent cell adhesion and are required for convergent extension in Xenopus., 2003; Current biology : CB. 13(14) 1182-91. PMID: 12867028

Davidson LA, Hoffstrom BG, Keller R, DeSimone DW, Mesendoderm extension and mantle closure in Xenopus laevis gastrulation: combined roles for integrin alpha(5)beta(1), fibronectin, and tissue geometry., 2002; Developmental biology. 242(2) 109-29. PMID: 11820810

Smith KM, Gaultier A, Cousin H, Alfandari D, White JM, DeSimone DW, The cysteine-rich domain regulates ADAM protease function in vivo., 2002; The Journal of cell biology. 159(5) 893-902. PMID: 12460986 | PMCID: PMC2173380

Alfandari D, Cousin H, Gaultier A, Smith K, White JM, Darribère T, DeSimone DW, Xenopus ADAM 13 is a metalloprotease required for cranial neural crest-cell migration., 2001; Current biology : CB. 11(12) 918-30. PMID: 11448768

Marsden M, DeSimone DW, Regulation of cell polarity, radial intercalation and epiboly in Xenopus: novel roles for integrin and fibronectin., 2001; Development (Cambridge, England). 128(18) 3635-47. PMID: 11566866

Lallier TE, DeSimone DW, Separation of neural induction and neurulation in Xenopus., 2000; Developmental biology. 225(1) 135-50. PMID: 10964470

Cohen MW, Hoffstrom BG, DeSimone DW, Active zones on motor nerve terminals contain alpha 3beta 1 integrin., 2000; The Journal of neuroscience : the official journal of the Society for Neuroscience. 20(13) 4912-21. PMID: 10864949