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.
|Yang, Liu; Kwon, Junghee; Popov, Yury et al. (2014) Vascular endothelial growth factor promotes fibrosis resolution and repair in mice. Gastroenterology 146:1339-50.e1|
|Guenzel, Adam J; Hillestad, Matthew L; Matern, Dietrich et al. (2014) Effects of adeno-associated virus serotype and tissue-specific expression on circulating biomarkers of propionic acidemia. Hum Gene Ther 25:837-43|
|Bi, Yan; Mukhopadhyay, Dhriti; Drinane, Mary et al. (2014) Endocytosis of collagen by hepatic stellate cells regulates extracellular matrix dynamics. Am J Physiol Cell Physiol 307:C622-33|
|White, Thomas A; LeBrasseur, Nathan K (2014) Myostatin and sarcopenia: opportunities and challenges - a mini-review. Gerontology 60:289-93|
|Peng, Ying; Clark, Karl J; Campbell, Jarryd M et al. (2014) Making designer mutants in model organisms. Development 141:4042-54|
|Yaqoob, Usman; Jagavelu, Kumaravelu; Shergill, Uday et al. (2014) FGF21 promotes endothelial cell angiogenesis through a dynamin-2 and Rab5 dependent pathway. PLoS One 9:e98130|
|Koh, Kwi Hye; Pan, Xian; Zhang, Wei et al. (2014) Krüppel-like factor 9 promotes hepatic cytochrome P450 2D6 expression during pregnancy in CYP2D6-humanized mice. Mol Pharmacol 86:727-35|
|Razumilava, Nataliya; Gradilone, Sergio A; Smoot, Rory L et al. (2014) Non-canonical Hedgehog signaling contributes to chemotaxis in cholangiocarcinoma. J Hepatol 60:599-605|
|Bhat, Mamatha; Chaiteerakij, Roongruedee; Harmsen, William S et al. (2014) Metformin does not improve survival in patients with hepatocellular carcinoma. World J Gastroenterol 20:15750-5|
|Tabibian, James H; O'Hara, Steven P; Splinter, Patrick L et al. (2014) Cholangiocyte senescence by way of N-ras activation is a characteristic of primary sclerosing cholangitis. Hepatology 59:2263-75|
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