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
Uthaya Kumar, Dinesh Babu; Chen, Chia-Lin; Liu, Jian-Chang et al. (2016) TLR4 Signaling via NANOG Cooperates With STAT3 to Activate Twist1 and Promote Formation of Tumor-Initiating Stem-Like Cells in Livers of Mice. Gastroenterology 150:707-19
Mandrekar, Pranoti; Bataller, Ramon; Tsukamoto, Hidekazu et al. (2016) Alcoholic hepatitis: Translational approaches to develop targeted therapies. Hepatology 64:1343-55
Chen, Chia-Lin; Uthaya Kumar, Dinesh Babu; Punj, Vasu et al. (2016) NANOG Metabolically Reprograms Tumor-Initiating Stem-like Cells through Tumorigenic Changes in Oxidative Phosphorylation and Fatty Acid Metabolism. Cell Metab 23:206-19
Harrall, Kylie K; Kechris, Katerina J; Tabakoff, Boris et al. (2016) Uncovering the liver's role in immunity through RNA co-expression networks. Mamm Genome 27:469-84
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
Kweon, Soo-Mi; Chi, Feng; Higashiyama, Reiichi et al. (2016) Wnt Pathway Stabilizes MeCP2 Protein to Repress PPAR-γ in Activation of Hepatic Stellate Cells. PLoS One 11:e0156111
Eguchi, Akiko; Lazaro, Raul G; Wang, Jiaohong et al. (2016) Extracellular vesicles released by hepatocytes from gastric infusion model of ALD contain a miRNA barcode that can be detected in blood. Hepatology :
Avila, Diana V; Barker, David F; Zhang, JingWen et al. (2016) Dysregulation of hepatic cAMP levels via altered Pde4b expression plays a critical role in alcohol-induced steatosis. J Pathol 240:96-107
Siddique, Hifzur R; Feldman, Douglas E; Chen, Chia-Lin et al. (2015) NUMB phosphorylation destabilizes p53 and promotes self-renewal of tumor-initiating cells by a NANOG-dependent mechanism in liver cancer. Hepatology 62:1466-79
Bayan, Jennifer-Ann; Peng, Zhechu; Zeng, Ni et al. (2015) Crosstalk Between Activated Myofibroblasts and β Cells in Injured Mouse Pancreas. Pancreas 44:1111-20

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