Non-Parenchymal Liver Cell Core proposed in this application, will provide to the alcohol research community, highly specialized services of isolation and culture of three types of non-parenchymal cells, sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells from normal, ethanol-fed, and pair-fed control rats. The principal and co-principal investigators have combined 28 years of experience in isolation of nonparenchymal liver cells and this expertise has served as a unique collaborative tool to support research activities by other investigators on and off campus. For the past two years, this technical resource has been partially subsidized by the NIDDK-funded University of Southern California (USC) Research Center for Liver Disease. However, the Core facility has grown to serve not only 5 USC investigators but also 7 investigators at other universities, and of the total 12 investigators, 10 investigators utilize the Core for alcohol- related research. The main objective of the proposal is to obtain a NIAAA Alcohol Research Resource Award to fully support the activities of the Core with a mission of promoting research on non-parenchymal liver cell biology in alcoholic liver disease (ALD), the field increasingly recognized as a mechanistically important area of research. Isolation of the three types of non-parenchymal liver cells is performed only in several laboratories in the country. Moreover, isolation of the cells from alcohol-fed animals is performed in even fewer laboratories. The Core will not only isolate the cells from normal rats but also work with the Animal Core of the NIAAA-funded USC-UCLA Research Center for Alcoholic Liver and Pancreatic Diseases (Alcohol Research Center), to prepare the cells from the intragastric ethanol infusion model of ALD. It is our goal that these unique services will stimulate the interest of scientists from alcohol and non-alcohol fields in applying novel questions and innovative techniques to research on non-parenchymal liver cell biology in ALD. In addition, the Core will provide scientific advice and hands-on training for the cell isolation procedures, to NIAAA-funded investigators who consider the study of alcohol and non-parenchymal liver cells as their primary interest. These goals will be achieved by close collaborations between the proposed Non- parenchymal Liver Cell Core and te existing Animal and Administrative Core facilities of the Alcohol Research Center, Headquartered at USC and directed by the Principal Investigator.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Health Services Research Review Subcommittee (AA)
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Russo, Denise A
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University of Southern California
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
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He, Lina; Gubbins, James; Peng, Zhechu et al. (2016) Activation of hepatic stellate cell in Pten null liver injury model. Fibrogenesis Tissue Repair 9:8
Page, Agata; Paoli, Pier; Moran Salvador, Eva et al. (2016) Hepatic stellate cell transdifferentiation involves genome-wide remodeling of the DNA methylation landscape. J Hepatol 64:661-73
DeLeve, Laurie D; Wang, Xiangdong; Wang, Lei (2016) VEGF-sdf1 recruitment of CXCR7+ bone marrow progenitors of liver sinusoidal endothelial cells promotes rat liver regeneration. Am J Physiol Gastrointest Liver Physiol 310:G739-46
Page, Agata; Paoli, Pier P; Hill, Stephen J et al. (2015) Alcohol directly stimulates epigenetic modifications in hepatic stellate cells. J Hepatol 62:388-97
Page, Agata; Mann, Derek A; Mann, Jelena (2014) The mechanisms of HSC activation and epigenetic regulation of HSCs phenotypes. Curr Pathobiol Rep 2:163-170
Yan, H-X; Wu, H-P; Zhang, H-L et al. (2013) DNA damage-induced sustained p53 activation contributes to inflammation-associated hepatocarcinogenesis in rats. Oncogene 32:4565-71
Ueno, Akiko; Lazaro, Raul; Wang, Ping-Yen et al. (2012) Mouse intragastric infusion (iG) model. Nat Protoc 7:771-81
Perugorria, Maria Jesus; Wilson, Caroline L; Zeybel, Mujdat et al. (2012) Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation. Hepatology 56:1129-39