Seok-Hyung Kim, Ph.D.

Seok Hyung Kim, Ph.D.Assistant Professor
Department: Regenerative Medicine & Cell Biology
Programs: Cell Injury, Inflammation, Fibrosis



Research Interests:

Alcoholic and non-alcoholic fatty liver diseases (FLD) are common chronic liver disorders. A substantial proportion of FLD patients develop an inflammatory response with hepatitis, leading to fibrosis, cirrhosis, liver failure and/or hepatocellular cancer.  Oxidative stress caused by accumulation of reactive oxygen/nitrogen species (ROS/RNS) and mitochondrial dysfunction has been implicated in the pathogenesis of both non-alcoholic and alcoholic FLD. The effect of obesity and environmental factors such as alcohol and high-fat diet in FLD are relatively well established. However, genetic determinants of FLD and advanced FLD, including steatohepatitis, fibrosis and hepatocellular carcinoma have not been systematically investigated. Previously, to identify novel genetic variants involved in liver disease, Dr. Kim’s group performed forward genetic screening of zebrafish mutants. Among 19 mutants identified from the screen, four novel mutants had hepatomegaly, steatosis, and hepatocellular injury and inflammation as well as evidence of mitochondrial oxidative stress. Dr. Kim and his team found that the proteins encoded by the mutant genes are directly or indirectly involved in mitochondrial respiration and maintenance. They also found activation of mTORC1 signaling pathway in the livers of all homozygous mutants.

Activation of mTORC1 signaling has been frequently found in FLD patients and might be involved in progression of liver disease, however mechanisms by which mTORC1 activation affect progression of liver disease are not well known. Dr. Kim’s recent data has demonstrated that mTORC1 activation is associated with an increase in oxidative stress and mitochondrial injury in the liver of mutants. His group also found evidence of hepatocellular injury and inflammation in adult heterozygous mutant zebrafish (all lines), supporting the possibility that humans who carry heterozygous mutations involved in mitochondrial function/homeostasis may be susceptible to FLD.

Thus, current investigations of Dr. Kim’s group are focused on understanding mechanisms of hepatocellular injury in the livers of these zebrafish mutants. Dr. Kim believes that this novel vertebrate model of liver disease will facilitate the identification of novel molecules that may be used to ameliorate advanced FLD. Therefore, his work and that of his group will validate the zebrafish model as one relevant to humans. The Analytical Cell Models Core will facilitate his use of CRISPR-Cas9 edited iPSCs to develop human liver cells, which will be essential for future studies. In addition, the Imaging and the Proteomics Cores will provide essential support for their projects.


PubMed Collection