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.
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.
|Malysz, John; Gibbons, Simon J; Saravanaperumal, Siva A et al. (2017) Conditional genetic deletion of Ano1 in interstitial cells of Cajal impairs Ca2+ transients and slow waves in adult mouse small intestine. Am J Physiol Gastrointest Liver Physiol 312:G228-G245|
|Tomita, Kyoko; Kohli, Rohit; MacLaurin, Brittany L et al. (2017) Mixed-lineage kinase 3 pharmacological inhibition attenuates murine nonalcoholic steatohepatitis. JCI Insight 2:|
|Rizvi, Sumera; Gores, Gregory J (2017) Emerging molecular therapeutic targets for cholangiocarcinoma. J Hepatol 67:632-644|
|Eisenman, S T; Gibbons, S J; Verhulst, P-J et al. (2017) Tumor necrosis factor alpha derived from classically activated ""M1"" macrophages reduces interstitial cell of Cajal numbers. Neurogastroenterol Motil 29:|
|Strege, Peter R; Gibbons, Simon J; Mazzone, Amelia et al. (2017) EAVK segment ""c"" sequence confers Ca2+-dependent changes to the kinetics of full-length human Ano1. Am J Physiol Gastrointest Liver Physiol 312:G572-G579|
|Schott, Micah B; Rasineni, Karuna; Weller, Shaun G et al. (2017) ?-Adrenergic induction of lipolysis in hepatocytes is inhibited by ethanol exposure. J Biol Chem 292:11815-11828|
|Alcaino, C; Farrugia, G; Beyder, A (2017) Mechanosensitive Piezo Channels in the Gastrointestinal Tract. Curr Top Membr 79:219-244|
|Mauer, Amy S; Hirsova, Petra; Maiers, Jessica L et al. (2017) Inhibition of sphingosine 1-phosphate signaling ameliorates murine nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 312:G300-G313|
|Sarmento, Olga F; Svingen, Phyllis A; Xiong, Yuning et al. (2017) The Role of the Histone Methyltransferase Enhancer of Zeste Homolog 2 (EZH2) in the Pathobiological Mechanisms Underlying Inflammatory Bowel Disease (IBD). J Biol Chem 292:706-722|
|O'Hara, Steven P; Splinter, Patrick L; Trussoni, Christy E et al. (2017) ETS Proto-oncogene 1 Transcriptionally Up-regulates the Cholangiocyte Senescence-associated Protein Cyclin-dependent Kinase Inhibitor 2A. J Biol Chem 292:4833-4846|
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