Analytic Core B provides support for a """"""""systems biology"""""""" approach to understanding colorectal cancer. This approach includes coordinating tissue collection, processing and distribution. In addition, the Analytic Core performs a variety of molecular morphological analyses including routine histology, immunohistochemistry, in situ hybridization, laser capture microdissection, RT-PCR, digital photography. The core also facilitates the study of genes that may underlie the molecular pathways that lead to colon cancer using zebrafish as a functional genomics model system. Core B offers three main services: (1) collection and storage of human colon tissue specimens;(2) characterization of human and murine colon tissues and (3) examination of relevant genes in zebrafish intestinal development. 1. Collection of Human Colon Tissue Specimens. Analytical Gore B works with the Huntsman Cancer Institute Tissue Acquistion and Distribution Core and Core C to provide centralized collection and distribution of tissues taken during colonoscopy or from surgical resections performed at participating hospitals. Informed consent is obtained prospectively for both groups of subjects. 2. Characterization of Human and Murine Colon Tissues. To maximize utilization of reagents derived from tissue specimens and to create uniform reagents, Analytcal Core B isolates DNAs and RNAs from normal colon, colon adenomas, and colon carcinomas taken from either humans or mice. This core stores and distributes RNA and DNA at the request of the project leaders. In addition, the core generates and maintains cDNA libraries from RNA taken from colon tumors, polyps and normal tissue. 3. Zebrafish Functional Genomics Resource. Zebrafish represent a tractable model system for quickly manipulating and identifying specific signaling pathways required for enterocyte differentiation. In view of the attributes of zebrafish as a model system. Core B provides gene maniplulation services either though overexpression or morpholino knock down to support our systems biology effort and to efficiently examine genetic pathways of intestinal differentiation.

Public Health Relevance

Our long-term goal is to facilitate the development of new preventive measures for colon adenoma formation by understanding the earliest cellular perturbations that follow APC mutation. This project supports our long-term goal in a number of ways. First, it will expand our understanding of how APC contributes to the development of normal intestinal epithelium. This understanding could support a testable clinical hypothesis using new combined therapies for preventing human colon cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA073992-12
Application #
8234103
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2011-03-01
Project End
2015-02-28
Budget Start
2011-03-01
Budget End
2012-02-29
Support Year
12
Fiscal Year
2011
Total Cost
$243,766
Indirect Cost
Name
University of Utah
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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Gan, Meng; Boothe, Dustin; Neklason, Deborah W et al. (2017) Outcomes and complications of radiation therapy in patients with familial adenomatous polyposis. J Gastrointest Oncol 8:643-649
Bice, Benjamin D; Stephens, Megan R; Georges, Stephanie J et al. (2017) Environmental Enrichment Induces Pericyte and IgA-Dependent Wound Repair and Lifespan Extension in a Colon Tumor Model. Cell Rep 19:760-773
Kanth, Priyanka; Bronner, Mary P; Boucher, Kenneth M et al. (2016) Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype. Cancer Prev Res (Phila) 9:456-65
Burt, Randall W (2016) Screening and Survival in Familial Adenomatous Polyposis. J Clin Gastroenterol 50:3-4
Samadder, N Jewel; Smith, Ken Robert; Hanson, Heidi et al. (2016) Familial Risk in Patients With Carcinoma of Unknown Primary. JAMA Oncol 2:340-6
Neklason, Deborah W; VanDerslice, James; Curtin, Karen et al. (2016) Evidence for a heritable contribution to neuroendocrine tumors of the small intestine. Endocr Relat Cancer 23:93-100
Li, Jun; Woods, Susan L; Healey, Sue et al. (2016) Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant. Am J Hum Genet 98:830-842
Samadder, N Jewel; Curtin, Karen; Pappas, Lisa et al. (2016) Risk of Incident Colorectal Cancer and Death After Colonoscopy: A Population-based Study in Utah. Clin Gastroenterol Hepatol 14:279-86.e1-2
Samadder, N Jewel; Neklason, Deborah W; Boucher, Kenneth M et al. (2016) Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial. JAMA 315:1266-75

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