Core 1 (Microfabication) The Microfabrication Core is a virtual infrastructure built upon the established microfabrication capacities in the laboratories of Drs. Fan and Levchenko, which have been geared toward innovative microfluidics and bioMEMS platforms for biomolecular and phenotypic analyses of cancer cells. It is also supported by the shared facility at Yale University West Campus. Specifically, the Core will support both Research Projects by fabricating and supplying nano-topographic patterned array substrata and microchip platforms as well as the assay services performed with them to i) measure single cancer cell migration and invasiveness in response to combination of external cues and genetic alterations to identify the molecular networks responsible for the P-A phenotypic switch, and ii) measure a panel of paracrine signals mediating heterotypic cell-cell communication that drive non-cell-autonomous mechanisms of invasive spread. In parallel, the Core will be a technology innovation center will develop novel technology platforms to enable new opportunities for scientific discoveries that cannot be achieved using the existing tools. Thus, the Core will be built upon substantial research in engineering innovation and represent an important component of the Yale's Cancer Systems Biology Center. Integration of the Core and the Research Projects will be performed according to the following research plan. First, fabrication of the nano-tographic patterned array substrata for directed cell migration measurement. Second, developing a microfluidic cell invasiveness assay chip via integrating the aforementioned substrata with microfluidic control of the cell media. This platform will be used to analyze melanoma and glioblastoma cell motility and quantify phenotypic heterogeneity (Project 1), and measure the influence of stromal cells and paracrine factors secreted therefrom (Project 2) on cancer cell invasiveness via further integration with the dual channel microfluidic co-culture device. Third, developing a microfluidic cell-cell communication assay microchip. This platform will be used to analyze how cell-cell communication alters the fate of cancer cells in a non-autonomous fashion (Project 2). The Core 1 will also function as a base to bridge engineering and biology to train cross-disciplinary cancer researchers and outreach activities. The Core will commit in trans-network collaboration and complement the resources cores in other U54 centers by offer microfabrication support.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA209992-02
Application #
9328005
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Shah, Sagar R; David, Justin M; Tippens, Nathaniel D et al. (2017) Brachyury-YAP Regulatory Axis Drives Stemness and Growth in Cancer. Cell Rep 21:495-507
Park, JinSeok; Holmes, William R; Lee, Sung Hoon et al. (2017) Mechanochemical feedback underlies coexistence of qualitatively distinct cell polarity patterns within diverse cell populations. Proc Natl Acad Sci U S A 114:E5750-E5759
Chow, Ryan D; Guzman, Christopher D; Wang, Guangchuan et al. (2017) AAV-mediated direct in vivo CRISPR screen identifies functional suppressors in glioblastoma. Nat Neurosci 20:1329-1341
Freed, Daniel M; Bessman, Nicholas J; Kiyatkin, Anatoly et al. (2017) EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics. Cell 171:683-695.e18
Smith, Chris L; Kilic, Onur; Schiapparelli, Paula et al. (2016) Migration Phenotype of Brain-Cancer Cells Predicts Patient Outcomes. Cell Rep 15:2616-24