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.
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.
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