In collaboration with cancer cell biologists at the Washington University School of Medicine and the University of Pennsylvania Abramson Cancer Center, as well as computational biophysicists at the University of Arizona, bioengineers and clinicians at Johns Hopkins University propose to create the Johns Hopkins Physical Sciences Oncology Center (PSOC). This PSOC will develop an integrated approach for a systematic, quantitative understanding of the forces mediating local invasion from the hypoxic primary tumor to distant organs, through single and collective invasion into the stromal matrix and confined migration along confining tracks, some of the early critical step in the metastatic cascade. To address the complexity of the combined effects of hypoxia, matrix microstructure and confinement on tumor cell invasion, we have developed three inter-related projects. Computational biophysicists will establish a computational core to systematically develop a quantitative understanding of forces in the metastatic cascade. PSOC projects will share innovative biophysical methods and experts. This PSOC takes a trans-disciplinary, integrated approach, combining the fields of physics, biomedical engineering, cancer biology, ecology, and clinical medicine, to transform our understanding of metastatic cancer, opening new paradigms for prognosis and treatment.

Public Health Relevance

In collaboration with cancer cell biologists at Washington University School of Medicine and the University of Pennsylvania Abramson Cancer Center, as well as computational biophysicists at the University of Arizona, bioengineers at Johns Hopkins University propose to create the Johns Hopkins Physical Sciences Oncology Center to develop an integrated approach for a systematic analysis and quantitative understanding of the physical forces mediating local tumor invasion.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA210173-05
Application #
10016193
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Zahir, Nastaran Z
Project Start
2016-08-29
Project End
2021-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Smith, Quinton; Rochman, Nash; Carmo, Ana Maria et al. (2018) Cytoskeletal tension regulates mesodermal spatial organization and subsequent vascular fate. Proc Natl Acad Sci U S A 115:8167-8172
Grither, Whitney R; Longmore, Gregory D (2018) Inhibition of tumor-microenvironment interaction and tumor invasion by small-molecule allosteric inhibitor of DDR2 extracellular domain. Proc Natl Acad Sci U S A 115:E7786-E7794
Ju, Julia A; Gilkes, Daniele M (2018) RhoB: Team Oncogene or Team Tumor Suppressor? Genes (Basel) 9:
Ye, I Chae; Fertig, Elana J; DiGiacomo, Josh W et al. (2018) Molecular Portrait of Hypoxia in Breast Cancer: A Prognostic Signature and Novel HIF-Regulated Genes. Mol Cancer Res 16:1889-1901
Neumann, Neil M; Perrone, Matthew C; Veldhuis, Jim H et al. (2018) Coordination of Receptor Tyrosine Kinase Signaling and Interfacial Tension Dynamics Drives Radial Intercalation and Tube Elongation. Dev Cell 45:67-82.e6
Smith, Quinton; Macklin, Bria; Chan, Xin Yi et al. (2018) Differential HDAC6 Activity Modulates Ciliogenesis and Subsequent Mechanosensing of Endothelial Cells Derived from Pluripotent Stem Cells. Cell Rep 24:895-908.e6
Rochman, Nash D; Popescu, Dan M; Sun, Sean X (2018) Ergodicity, hidden bias and the growth rate gain. Phys Biol 15:036006
Vig, Dhruv K; Hamby, Alex E; Wolgemuth, Charles W (2017) Cellular Contraction Can Drive Rapid Epithelial Flows. Biophys J 113:1613-1622
Tao, Jiaxiang; Li, Yizeng; Vig, Dhruv K et al. (2017) Cell mechanics: a dialogue. Rep Prog Phys 80:036601
Lewis, Daniel M; Blatchley, Michael R; Park, Kyung Min et al. (2017) O2-controllable hydrogels for studying cellular responses to hypoxic gradients in three dimensions in vitro and in vivo. Nat Protoc 12:1620-1638

Showing the most recent 10 out of 21 publications