In consortium with researchers at Washington University School of Medicine, the University of Connecticut Health Center, the University of North Carolina School of Medicine, and the University of Florida, we propose to create a highly integrated Center for Cancer Physics at Johns Hopkins University. Our integrated approach will allow a systematic analysis and quantitative understanding of how various mechanical stimuli - cell-cell adhesive forces, compressional forces, interstitial fluid flow causing shear stresses and hydrostatic pressure, adhesive forces between cell and substrate, cell-mediated traction and protrusive forces within the matrix, steric forces during extravasation and intravasation, shear forces in the circulatory system - modulate angiogenesis, cell dissociation from the primary tumor, three-dimensional motility in the matrix, basement membrane and vascular invasion, tumor cell-host cell interactions in the circulatory system, and cell proliferation at the secondary tumor site. To address the complexity of the role of forces in cancer, we have developed three interrelated projects. To overcome the lack of predictive computational models of cancer, computational and experimental biophysicists as well as cancer biologists will work together in the Center to systematically develop a quantitative understanding of forces in the metastatic cascade. To overcome the lack of consistency in the use of models and biophysical methods, the projects will use the same biophysical methods and the same cancer cell lines. To overcome language and cultural barriers between cancer biologists and physicists/engineers, the Center will establish a comprehensive predoctoral and postdoctoral multidisciplinary training program. Johns Hopkins University cancer biologists, engineers, and physicists in the Center will work in the same laboratories.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
3U54CA143868-05S1
Application #
8722803
Study Section
Special Emphasis Panel (ZCA1-SRLB-9 (O1))
Program Officer
Ogunbiyi, Peter
Project Start
2009-09-28
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$61,526
Indirect Cost
$21,074
Name
Johns Hopkins University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Park, JinSeok; Kim, Deok-Ho; Kim, Hong-Nam et al. (2016) Directed migration of cancer cells guided by the graded texture of the underlying matrix. Nat Mater 15:792-801
Zhang, Kun; Grither, Whitney R; Van Hove, Samantha et al. (2016) Mechanical signals regulate and activate SNAIL1 protein to control the fibrogenic response of cancer-associated fibroblasts. J Cell Sci 129:1989-2002
He, Lijuan; Chen, Weitong; Wu, Pei-Hsun et al. (2016) Local 3D matrix confinement determines division axis through cell shape. Oncotarget 7:6994-7011
Hielscher, Abigail; Ellis, Kim; Qiu, Connie et al. (2016) Fibronectin Deposition Participates in Extracellular Matrix Assembly and Vascular Morphogenesis. PLoS One 11:e0147600
Ruhland, Megan K; Loza, Andrew J; Capietto, Aude-Helene et al. (2016) Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis. Nat Commun 7:11762
Luo, Xianmin; Fu, Yujie; Loza, Andrew J et al. (2016) Stromal-Initiated Changes in the Bone Promote Metastatic Niche Development. Cell Rep 14:82-92
Lee, Pilhwa; Wolgemuth, Charles W (2016) Physical Mechanisms of Cancer in the Transition to Metastasis. Biophys J 111:256-66
Semenza, Gregg L (2016) Novel strategies for cancer therapy. J Mol Med (Berl) 94:119-20
Semenza, Gregg L (2016) The hypoxic tumor microenvironment: A driving force for breast cancer progression. Biochim Biophys Acta 1863:382-91
Lan, Tian; Cheng, Kai; Ren, Tina et al. (2016) Displacement correlations between a single mesenchymal-like cell and its nucleus effectively link subcellular activities and motility in cell migration analysis. Sci Rep 6:34047

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