Research Medicine, Biochemical & Molecular Biology
Keck School of Medicine of USC
- Organelle ER Stress, UPR and Liver Diseases;
- Hepatotoxicity of alcohol and anti-HIV/HCV Drugs;
- Tackling Alcohol Intoxication with Nanotechnology
Research OverviewHeavy or long-term alcohol consumption is a major cause of acute and chronic liver disease worldwide. Alcohol induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis has recently been established as a significant mechanism contributing to liver diseases. 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 alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur 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 may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for prevention of liver cancer in alcoholics.
(1) Advance & New Concept in Alcohol-Induced Organelle Stress, UPR and Organ Damage.
Biomolecules 2015; 5(2):1099. PMID: 26047032.
(2) Effects of Alcohol and Anti-HIV Drugs on Cellular Stress Responses in Primary Liver Cells.
Alcohol Clin Exp Res. 2015; 39(1):11.
(3) New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases.
Int. J. of Hepatology, vol. 2014; 513787; PMID: 2486870
(4) Critical Role of GRP78 in Pulmonary Microvascular Remodeling
Gene. 2014; 545(1):156; PMID: 24768185
(5) Expression of GRP78 in hepatopulmonary syndrome.
Gene. 2014; 537:115-119; PMID: 24334118
(6) Altered Methylation of ERAD in Alcohol-induced Liver Tumors.
Frontiers in Genetics 2013; 4: 224; PMCID: PMC3813967
(7) Enzyme Nanocomplexes as Antidotes for Alcohol Intoxication
Nature Nanotech. 2013; 8:187
(8) ER stress, Cyclin D, ERα variants, and Liver Tumorigenesis
J Gastro. Hepatol. 2013; 28(3):576
(9) Tregs, MMP9/13, TGF-β and acute liver injury.
J Mol Cell Biol. 2013; 5(6):369. PMID: 24280647