Celeste M. Nelson
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 (609) 258-8851 |
 Engineering Quadrangle, A321 |
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Lab (609) 258-8222 |
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Faculty Assistant
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Virginia Czarnecki
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(609) 258-1830 |
Research Focus
Tissue Morphodynamics
Our group seeks to answer the following fundamental questions: How are the final architectures of tissues and organs determined? Specifically, how do individual cell—the building blocks of these materials—integrate complex biological signals (both biochemical and mechanical) dynamically and spatially within tissues to direct the development of organs?
The answers to these questions have broad ramifications, from understanding the fundamental mechanisms of development, to delineating the developmental control processes that are circumvented by cancer and other diseases, to elucidating new paradigms required for successful therapeutic approaches in regenerative medicine and tissue engineering. Because of the complexity of the interacting pathways and three-dimensional (3D) nature of developing tissues, this problem requires an interdisciplinary approach, combining expertise from the cell biology, developmental biology, and engineering communities. Our group works at the interface of these disciplines, developing tools to engineer organotypic culture models that mimic tissue development, enabling rigorous quantitative analysis and computational predictions of the dynamics of morphogenesis. Our current focus is on sophisticated mammalian cell culture and mouse models of normal branching morphogenesis (ie, the developmental process that builds the lung, kidney, and mammary gland) and abnormal neoplastic growth.
Cellular cooperation within 3D tissues
How do cells cooperate and integrate to build complex tissue geometries, such as the branching architectures of the lung, kidney, and mammary gland? The most straightforward way to address this question would be to manipulate individual cells at specific locations within a tissue at will—reproducibly and with high precision. We accomplish this by using microfabrication approaches to recreate 3D mammalian tissue architecture in culture. Current challenges include: (1) understanding the dynamics of individual cells during morphogenesis; (2) understanding the roles of different cell types within an organ during development; (3) defining the role of the cellular microenvironment in normal development and neoplastic progression.
Biochemical and mechanical signal integration
What signals determine final tissue geometry? Long-range communication between individual cells within a tissue is critical for determining pattern formation during morphogenesis. We have shown that pattern formation and symmetry breaking are determined in part by long-range transmission of mechanical stresses and autocrine morphogen gradients; these gradients are determined by the structure of the tissue, forming a feedback system during morphogenesis. We use experimental and computational approaches to determine the relative roles of morphogen and mechanical gradients during tissue development.
Selected Publications
Zhu W, Nelson CM. (2013) PI3K regulates branch initiation and extension of cultured mammary epithelia via Akt and Rac1 respectively. Dev Biol. S0012-1606(13)00223-6. [Epub ahead of print]
Zhu W, Nelson CM. (2013) Adipose and mammary epithelial tissue engineering. Biomatter. 3: e24630. Pubmed
Radisky DC, Nelson CM. (2013) Regulation of mechanical stress by mammary epithelial tissue structure controls breast cancer cell invasion. Oncotarget. 4: 498-9. Pubmed
Gleghorn JP, Manivannan S, Nelson CM. (2013) Quantitative approaches to uncover physical mechanisms of morphogenesis. Curr. Opin. Biotechnol. S0958-1669(13)00087-6. PubMed
Chen QK, Lee K, Radisky DC, Nelson CM. (2013) Extracellular matrix proteins regulate epithelial-mesenchymal transition in mammary epithelial cells. Differentiation. S0301-4681(13)00025-X. Pubmed
Mori H, Lo AT, Ghajar CM, ... Nelson C.M. ... Bissell M.J. (2013) Transmembrane/cytoplasmic, rather than catalytic, domains of Mmp14 signal to MAPK activation and mammary branching morphogenesis via binding to integrin beta1. Development 140: 343-352. Pubmed
Boghaert E, Gleghorn JP, Lee K, Gjorevski N, Radisky DC, Nelson CM. (2012) Host epithelial geometry regulates breast cancer cell invasiveness. Proc Natl Acad Sci. 109: 19632-19637. Pubmed
Manivannan S, Nelson CM. (2012) Dynamics of branched tissue assembly. Stem Cell Res Ther. 3: 42. Pubmed
Lee K, Chen QK, Lui C, Cichon MA, Radisky DC, Nelson CM. (2012) Matrix compliance regulates Rac1b localization, NADPH oxidase assembly, and epithelial-mesenchymal transition. Mol Biol Cell. 23: 4097-4108. Pubmed
Nelson CM, Gorsuch RA, Bailey TJ, Ackerman KM, Kassen SC, Hyde DR. (2012) Stat3 defines three populations of Müller glia and is required for initiating maximal Müller glia proliferation in the regenerating zebrafish retina. J Comp Neurol. 520: 4294-311. Pubmed
Zhu W, Nelson CM. (2012) PI3K signaling in the regulation of branching morphogenesis. Biosystems. 403-11. Pubmed
Chung JW, Lee K, Neikirk C, Nelson CM, Priestley RD. (2012) Photoresponsive coumarin-stabilized polymeric nanoparticles as a detectable drug carrier. Small. 8: 1693-1700. PubMed
Gleghorn JP, Kwak J, Pavlovich AL, Nelson CM. (2012) Inhibitory morphogens and monopodial branching of the embryonic chicken lung. Dev Dyn. 241: 852-862. PubMed
Lee K, Nelson CM. (2012) New insights into the regulation of epithelial-mesenchymal transition and tissue fibrosis. Int Rev Cell Mol Biol. 294: 171-221. PubMed
Nelson CM, Gleghorn JP. (2011) Sculpting organs: Mechanical regulation of tissue development. Annu Rev Biomed Eng. 14: 129-154. Pubmed
Gjorevski N, Nelson CM. (2011) Integrated morphodynamic signalling of the mammary gland. Nat Rev Mol Cell Biol. 12: 581-593. PubMed
Gjorevski N, Boghaert E, Nelson CM. (2011) Regulation of epithelial-mesenchymal transition by transmission of mechanical stress through epithelial tissues. Cancer Microenviron. 5: 29-38. PubMed
Lee K, Gjorevski N, Boghaert E, Radisky DC, Nelson CM. (2011) Snail1, Snail2, and E47 promote mammary epithelial branching morphogenesis. EMBO J. 30: 2662-2674. PubMed
Gomez EW, Nelson CM. (2010) Lithographically defined two- and three-dimensional tissue microarrays. Methods Mol Biol. 671: 107-116. PubMed
Gjorevski N, Nelson CM. (2010) Branch formation during organ development. Wiley Interdiscip Rev Syst Biol Med. 2: 734-741. PubMed
Gjorevski N, Nelson CM. (2010) The mechanics of development: Models and methods for tissue morphogenesis. Birth Defects Res C Embryo Today. 90: 193-202. PubMed
Gjorevski N, Nelson CM. (2010) Endogenous patterns of mechanical stress are required for branching morphogenesis. Integr Biol (Camb). 2: 424-434. PubMed
Gomez EW, Chen QK, Gjorevski N, Nelson CM. (2010) Tissue geometry patterns epithelial-mesenchymal transition via intercellular mechanotransduction. J Cell Biochem. 110: 44-51. PubMed
Gjorevski N, Nelson CM. (2009) Bidirectional extracellular matrix signaling during tissue morphogenesis. Cytokine Growth Factor Rev. 20: 459-465. PubMed
Nelson CM. (2009) Geometric control of tissue morphogenesis. Biochim Biophys Acta. 1793: 903-910. PubMed
Nelson CM, Inman JL, Bissell MJ. (2008) Three-dimensional lithographically-defined organotypic tissue arrays for quantitative analysis of morphogenesis and neoplastic progression. Nat Protoc. 3: 674-678. PubMed
Nelson CM, VanDuijn MM, Inman JL, Fletcher DA, Bissell MJ. (2006) Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures. Science 314: 298-300. PubMed
Nelson CM, Tien J. (2006) Microstructured extracellular matrices in tissue engineering and development. Curr Opin Biotech. 17: 518-523. PubMed
Nelson CM, Bissell MJ. (2006) Of extracellular matrix, scaffolds, and signaling: Tissue architecture regulates development, homeostasis, and cancer. Annu Rev Cell Dev Biol. 22: 287-309. PubMed
Nelson CM, Jean RP, Tan JL, Liu WF, Sniadecki NJ, Spector AA, Chen CS. (2005) Emergent patterns of growth controlled by multicellular form and mechanics. Proc Natl Acad Sci 102: 11594-11599. PubMed
Radisky DC, Levy DD, Littlepage LE, Liu H, Nelson CM, Fata JE, Leake D, Godden EL, Albertson DG, Nieto MA, Werb Z, Bissell MJ. (2005) Rac1b and reactive oxygen species mediate MMP3-induced EMT and genomic instability. Nature 436: 123-127. PubMed
McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineagecommitment. Dev Cell 6: 483-495. PubMedNelson CM, Chen CS. (2003) VE-cadherin simultaneously stimulates and inhibits cell proliferation by altering cytoskeletal structure and tension. J Cell Sci. 116: 3571-3581. PubMed
