PIBBS Mentor; Professor
Research Medicine, Biochemical & Molecular Biology
Keck School of Medicine of USC
- Organelle (ER/Golgi/Lysosome) Stress and Liver Diseases;
- Hepatotoxicity of alcohol and anti-HIV/HCV/TB Drugs;
- Tackling Alcohol Intoxication with Nanotechnology
Research OverviewHeavy or long-term alcohol consumption is a major cause of acute and chronic liver disease (ALD) worldwide. Alcohol induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis has been established as a significant mechanism contributing to ALD. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in ALD depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors (e.g. drug abuse), cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress occurs more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress directly lead to development of hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways in ALD will uncover potential therapeutic targets for prevention/curing of ALD.
RECENT PUBLICATIONS (see ALL via PubMed or GoogleScholar):
(1) Effect of artesunate supplementation on bacterial translocation and dysbiosis of gut microbiota in rats with liver cirrhosis. World J Gastroenterol. 2016; 22(10):2949; PMID: 26973391.
(2) Advance & New Concept in Alcohol-Induced Organelle Stress, UPR and Organ Damage. Biomolecules 2015; 5(2):1099. PMID: 26047032.
(3) Effects of Alcohol and Anti-HIV Drugs on Cellular Stress Responses in Primary Liver Cells. Alcohol Clin Exp Res. 2015; 39(1):11.
(4) Enhanced expression of GRP78 correlates with malondialdehyde levels… Exp Ther Med. 2015;10(6):2119. PMID: 26668603.
(5) Overexpression of GRP78 promotes cardiomyocyte apoptosis in a rat model of liver cirrhosis. Int J Clin Exp Pathol 2015; 8(8): 9256; PMID:26464674.
(6) New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases. Int. J. of Hepatology, vol. 2014; 513787; PMID: 2486870
(7) Critical Role of GRP78 in Pulmonary Microvascular Remodeling. Gene. 2014; 545(1):156; PMID: 24768185
(8) Expression of GRP78 in hepatopulmonary syndrome. Gene. 2014; 537:115-119; PMID: 24334118
(9) Altered Methylation of ERAD in Alcohol-induced Liver Tumors. Frontiers in Genetics 2013; 4: 224; PMCID: PMC3813967
(10) Enzyme Nanocomplexes as Antidotes for Alcohol Intoxication. Nature Nanotech. 2013; 8:187
(11) ER stress, Cyclin D, ERα variants, and Liver Tumorigenesis. J Gastro. Hepatol. 2013; 28(3):576
(12) Tregs, MMP9/13, TGF-β and acute liver injury. J Mol Cell Biol. 2013; 5(6):369. PMID: 24280647