Abstract

High-throughput screening (NTS) is a means of rapidly assessing the ability of hundreds of thousands of chemical compounds to affect biological systems for the purpose of accelerating medical research. We propose an HTS core the goal of which is to enable Gl SPORE investigators to discover chemical tools to promote better understanding of colorectal cancer physiology and potentially to help reveal novel targets and therapeutic opportunities. Using state-of-the-art HTS technologies and working with Gl SPORE investigators, the Vanderbilt Institute of Chemical Biology's HTS facility has developed and validated HTS-compatible assays aimed at discovering chemical tools relevant to: 1) E-cadherin regulation in the human colon cancer cell line, SW620;2) axin and (3-catenin stability in a novel in vitro assay system;and 3) p120's role in modulating E-cadherin activity and adherens junction formation in the Colo205 cell line. We present data demonstrating our ability to perform the HTS assays, discover compounds that affect the systems noted above, and we detail our plans to use the products of the HTS to further the aims of the Gl SPORE.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA095103-08
Application #
7813824
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
8
Fiscal Year
2009
Total Cost
$100,677
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212

  Publications

Roberts, Jordan; Gonzalez, Raul S; Revetta, Frank et al. (2018) Mesenteric tumour deposits arising from small-intestine neuroendocrine tumours are frequently associated with fibrosis and IgG4-expressing plasma cells. Histopathology 73:795-800
Gibson, William E; Gonzalez, Raul S; Cates, Justin M M et al. (2018) Hepatic micrometastases are associated with poor prognosis in patients with liver metastases from neuroendocrine tumors of the digestive tract. Hum Pathol 79:109-115
Fenix, Aidan M; Neininger, Abigail C; Taneja, Nilay et al. (2018) Muscle-specific stress fibers give rise to sarcomeres in cardiomyocytes. Elife 7:
Wang, Jing; Zhao, Yue; Zhou, Xiaofan et al. (2018) Nascent RNA sequencing analysis provides insights into enhancer-mediated gene regulation. BMC Genomics 19:633
Burns, Michael C; Howes, Jennifer E; Sun, Qi et al. (2018) High-throughput screening identifies small molecules that bind to the RAS:SOS:RAS complex and perturb RAS signaling. Anal Biochem 548:44-52
Herring, Charles A; Banerjee, Amrita; McKinley, Eliot T et al. (2018) Unsupervised Trajectory Analysis of Single-Cell RNA-Seq and Imaging Data Reveals Alternative Tuft Cell Origins in the Gut. Cell Syst 6:37-51.e9
Hinger, Scott A; Cha, Diana J; Franklin, Jeffrey L et al. (2018) Diverse Long RNAs Are Differentially Sorted into Extracellular Vesicles Secreted by Colorectal Cancer Cells. Cell Rep 25:715-725.e4
Weigl, Korbinian; Thomsen, Hauke; Balavarca, Yesilda et al. (2018) Genetic Risk Score Is Associated With Prevalence of Advanced Neoplasms in a Colorectal Cancer Screening Population. Gastroenterology 155:88-98.e10
Schulte, Michael L; Fu, Allie; Zhao, Ping et al. (2018) Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models. Nat Med 24:194-202
Zhao, Shilin; Li, Chung-I; Guo, Yan et al. (2018) RnaSeqSampleSize: real data based sample size estimation for RNA sequencing. BMC Bioinformatics 19:191

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