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 #
5P50CA095103-07
Application #
7620044
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
7
Fiscal Year
2008
Total Cost
$99,828
Indirect Cost

  Institution

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

  Publications

Singh, Kshipra; Coburn, Lori A; Asim, Mohammad et al. (2018) Ornithine Decarboxylase in Macrophages Exacerbates Colitis and Promotes Colitis-Associated Colon Carcinogenesis by Impairing M1 Immune Responses. Cancer Res 78:4303-4315
Idrees, Kamran; Padmanabhan, Chandrasekhar; Liu, Eric et al. (2018) Frequent BRAF mutations suggest a novel oncogenic driver in colonic neuroendocrine carcinoma. J Surg Oncol 117:284-289
Zhang, Qin; Jeppesen, Dennis K; Higginbotham, James N et al. (2018) Mutant KRAS Exosomes Alter the Metabolic State of Recipient Colonic Epithelial Cells. Cell Mol Gastroenterol Hepatol 5:627-629.e6
Choksi, Yash A; Reddy, Vishruth K; Singh, Kshipra et al. (2018) BVES is required for maintenance of colonic epithelial integrity in experimental colitis by modifying intestinal permeability. Mucosal Immunol 11:1363-1374
Saito-Diaz, Kenyi; Benchabane, Hassina; Tiwari, Ajit et al. (2018) APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway. Dev Cell 44:566-581.e8
Davenport, James R; Su, Timothy; Zhao, Zhiguo et al. (2018) Modifiable lifestyle factors associated with risk of sessile serrated polyps, conventional adenomas and hyperplastic polyps. Gut 67:456-465
Liu, Qi; Herring, Charles A; Sheng, Quanhu et al. (2018) Quantitative assessment of cell population diversity in single-cell landscapes. PLoS Biol 16:e2006687
Means, Anna L; Freeman, Tanner J; Zhu, Jing et al. (2018) Epithelial Smad4 Deletion Up-Regulates Inflammation and Promotes Inflammation-Associated Cancer. Cell Mol Gastroenterol Hepatol 6:257-276
Weiss, Vivian L; Kiernan, Colleen; Wright, Jesse et al. (2018) Fine-Needle Aspiration-Based Grading of Pancreatic Neuroendocrine Neoplasms Using Ki-67: Is Accurate WHO Grading Possible on Cytologic Material? J Am Soc Cytopathol 7:154-459
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

Showing the most recent 10 out of 447 publications