The C-SiG Genetics and Model Systems Core facilitates access to genetic tools and model systems for digestive disease-related research projects. Genetic manipulation is a critical approach from biological modeling to establishing and testing critical molecular signaling pathways in both normal and clinically relevant disease states. Genetic tools are extremely dynamic, with new technologies emerging every year. The Core provides current, emerging, and future genetic technologies while facilitating access to a full range of model systems including mouse, zebrafish, and rat. The Core Director, Dr. Stephen Ekker, is a well-established geneticist with extensive expertise using a variety of model systems. The Core has focused our original Specific Aims on tangible deliverables to better serve the C-SiG membership. Thus, the current SPECIFIC AIMS of the C-SiG Genetics and Model Systems Core are three-fold. First, to accelerate research by connecting and educating members to genetics and model systems tools. Second, to deliver new genetics and model systems tools/technologies that are needed by C-SiG members. Third, to establish cutting-edge genetic tools for genome editing including zinc finger nucleases (ZFNs), TALENs, Cas9 Custom Restriction Enzyme System (CRlSPRs) and future locus-specific genome editing tools that can be applied to model organism development including zebrafish, rats, mice and Drosophila.
These aims will be accomplished by: i) Directly generating custom reagents including transposon clones, BAC clones, and TALENs for top-priority projects;ii) Providing education through core-sponsored seminars, Web site, and presentations to C-SiG Member laboratories;iii) Providing consultative services by connecting C-SiG members to genetics tools and institutional infrastructures directly and through a novel online reagent hub; and, iv) Developing model experimental systems, including zebrafish and genetically manipulated mice, flies, and rats, directly and by facilitating internal and external collaborative partnerships that benefit C-SiG members. Tiie C-SiG Genetics and Model Systems Core services have been used by 55% of Center members and supported 18 publications.

Public Health Relevance

Gastrointestinal diseases and their complications have a significant effect on public health and health care utilization costs. The C-SiG Genetics and Model Systems Core supports scientific advancements of C-SiG members that are critically important for furthering understanding of the mechanisms that underlie digestive diseases, which can lead to practical applications for the diagnosis, prevention, monitoring and treatment of human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
2P30DK084567-06
Application #
8737731
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Banales, Jesus M; Marzioni, Marco; LaRusso, Nicholas F et al. (2018) Cholangiocytes in health and disease: From basic science to novel treatments. Biochim Biophys Acta Mol Basis Dis 1864:1217-1219
Tarragó, Mariana G; Chini, Claudia C S; Kanamori, Karina S et al. (2018) A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline. Cell Metab 27:1081-1095.e10
Kim, Minsoo; Druliner, Brooke R; Vasmatzis, Nikolaos et al. (2018) Inferring modes of evolution from colorectal cancer with residual polyp of origin. Oncotarget 9:6780-6792
Druliner, Brooke R; Wang, Panwen; Bae, Taejeong et al. (2018) Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations. Sci Rep 8:3161
Mansini, Adrian P; Lorenzo Pisarello, Maria J; Thelen, Kristen M et al. (2018) MicroRNA (miR)-433 and miR-22 dysregulations induce histone-deacetylase-6 overexpression and ciliary loss in cholangiocarcinoma. Hepatology 68:561-573
Moncsek, Anja; Al-Suraih, Mohammed S; Trussoni, Christy E et al. (2018) Targeting senescent cholangiocytes and activated fibroblasts with B-cell lymphoma-extra large inhibitors ameliorates fibrosis in multidrug resistance 2 gene knockout (Mdr2-/- ) mice. Hepatology 67:247-259
Allen, Alina M; Shah, Vijay H; Therneau, Terry M et al. (2018) The role of 3D-MRE in the diagnosis of NASH in obese patients undergoing bariatric surgery. Hepatology :
Dhanasekaran, Renumathy; Nault, Jean-Charles; Roberts, Lewis R et al. (2018) Genomic Medicine and Implications for Hepatocellular Carcinoma Prevention and Therapy. Gastroenterology :
Sugihara, Takaaki; Werneburg, Nathan W; Hernandez, Matthew C et al. (2018) YAP Tyrosine Phosphorylation and Nuclear Localization in Cholangiocarcinoma Cells Are Regulated by LCK and Independent of LATS Activity. Mol Cancer Res 16:1556-1567
Rizvi, Sumera; Fischbach, Samantha R; Bronk, Steven F et al. (2018) YAP-associated chromosomal instability and cholangiocarcinoma in mice. Oncotarget 9:5892-5905

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