The Non-Parenchymal Liver Cell Core has been a catalyst for both a prolific growth of cell-type specific research by center and non-center investigators and successful career developments of young investigators. During the current funding cycle, the core has served 30 investigators by performing 2,304 isolations of rat and mouse hepatic stellate cells (HSC), sinusoidal endothelial cells (SEC), Kupffer cells (KC), and hepatocytes. These core services have supported 21 peer-reviewed publications and 14 grant acquisitions or renewals, plus 5 pending grant applications. As a testament to the support for young career developments, the core has facilitated successful acquisition of two KGB, one K99 and four first ROI awards by young investigators. In addition, the core continued to serve as a national resource by supporting 11 non-center investigators from 9 institutions across the nation. The core has experienced a 62% increase in the volume of services rendered in most recent 3 years, due in part to increased requests for isolation of mouse liver cells. The core has also incorporated new innovative techniques: 1) automated MACS (magnetic cell sorting)-based isolation of rat and mouse SEC;2) FACS (fluorescence-activated cell sorting)-based isolation of HSC from Tg mice expressing GFP under the control of type I collagen promoter (Coll-GFP) which allows collection of heterogeneous populations of HSC from a normal mouse liver and vitamin A-depleted, activated HSC from a mouse intragastric ethanol infusion model of steatohepatitis;and 3) a hypoxia chamber-shuttle box system to facilitate culture and manipulations of the cells in a manner which reproduces alcohol-induced liver hypoxia in vivo. The core is committed to continued provision of unique and invaluable services of liver cell isolation from normal and diseased rodents to promote cell-type specific research on ALD and cirrhosis at both regional and national levels.

Public Health Relevance

The non-parenchymal liver cell core laboratory proposed in this grant helps researchers to discover how harmful effects are produced by different cell types in the liver, causing alcohol-associated liver diseases and cirrhosis. New information generated by these studies with support from the core, will lead to identification of new treatment modalities for the diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Resource-Related Research Projects (R24)
Project #
5R24AA012885-13
Application #
8474672
Study Section
Special Emphasis Panel (ZAA1-GG (01))
Program Officer
Gao, Peter
Project Start
2001-06-01
Project End
2016-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
13
Fiscal Year
2013
Total Cost
$406,766
Indirect Cost
$159,430
Name
University of Southern California
Department
Pathology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Khanova, Elena; Wu, Raymond; Wang, Wen et al. (2018) Pyroptosis by caspase11/4-gasdermin-D pathway in alcoholic hepatitis in mice and patients. Hepatology 67:1737-1753
Gajendiran, Priya; Vega, Leonel Iglesias; Itoh, Kie et al. (2018) Elevated mitochondrial activity distinguishes fibrogenic hepatic stellate cells and sensitizes for selective inhibition by mitotropic doxorubicin. J Cell Mol Med 22:2210-2219
Wu, Raymond; Murali, Ramachandran; Kabe, Yasuaki et al. (2018) Baicalein Targets GTPase-Mediated Autophagy to Eliminate Liver Tumor-Initiating Stem Cell-Like Cells Resistant to mTORC1 Inhibition. Hepatology 68:1726-1740
Yang, Zemin; Liu, Yu; Qin, Lan et al. (2017) Cathepsin H-Mediated Degradation of HDAC4 for Matrix Metalloproteinase Expression in Hepatic Stellate Cells: Implications of Epigenetic Suppression of Matrix Metalloproteinases in Fibrosis through Stabilization of Class IIa Histone Deacetylases. Am J Pathol 187:781-797
Machida, Keigo (2017) Existence of cancer stem cells in hepatocellular carcinoma: myth or reality? Hepatol Int 11:143-147
Lai, Keane K Y; Kweon, Soo-Mi; Chi, Feng et al. (2017) Stearoyl-CoA Desaturase Promotes Liver Fibrosis and Tumor Development in Mice via a Wnt Positive-Signaling Loop by Stabilization of Low-Density Lipoprotein-Receptor-Related Proteins 5 and 6. Gastroenterology 152:1477-1491
Zeybel, M├╝jdat; Luli, Saimir; Sabater, Laura et al. (2017) A Proof-of-Concept for Epigenetic Therapy of Tissue Fibrosis: Inhibition of Liver Fibrosis Progression by 3-Deazaneplanocin A. Mol Ther 25:218-231
Eguchi, Akiko; Lazaro, Raul G; Wang, Jiaohong et al. (2017) Extracellular vesicles released by hepatocytes from gastric infusion model of alcoholic liver disease contain a MicroRNA barcode that can be detected in blood. Hepatology 65:475-490
Chen, Chia-Lin; Huang, Jeffrey Y; Wang, Chun-Hsiang et al. (2017) Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2. Nat Commun 8:13882
Li, Yuchang; Lua, Ingrid; French, Samuel W et al. (2016) Role of TGF-? signaling in differentiation of mesothelial cells to vitamin A-poor hepatic stellate cells in liver fibrosis. Am J Physiol Gastrointest Liver Physiol 310:G262-72

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