Division of Nephrology
The Kim laboratory focuses on molecular mechanisms involved in inherited metabolic liver diseases using zebrafish. Through the forward genetic screening of mutant zebrafish, his lab identified 19 novel mutants, including known genetic disorders with liver defects such as Tuberous Sclerosis Complex, Multiple Acyl-CoA dehydrogenase deficiency and Alper's syndrome. Kim has found mTORC1 signaling plays important role in progression of liver injury in those mutants. One recent study has focused on the mechanism of sphingolipids accumulation in 3-ketodihydrosphingosine reductase (kdsr) mutant and has found that sphingosine kinase 2 played a key role in progression of liver disease from steatosis to steatohepatitis in the kdsr mutant.
The other major topic of Kim’s research is to determine whether heterozygous mutations in those mutants are novel genetic risk factors underlying development of alcoholic/non-alcoholic fatty liver disease in adults. Importantly, the Kim lab has found heterozygous mutations in certain genes are sufficient to induce steatohepatitis phenotype in adult zebrafish, which supporting the hypothesis that those heterozygous mutants are prone to develop advanced liver disease under a certain stress condition such as high-fat diet or chronic alcohol consumption. Thus, genetic mutations found in inherited metabolic disease models could be novel genetic risk factors in human. Additionally, the Kim lab has successfully established both high-fat diet and alcoholic induced steatohepatitis model in adult zebrafish, recapitulating pathology and metabolic context of liver disease in patients. Because adult zebrafish has not been used as model of chronic liver disease, his research will bring zebrafish as an alternative vertebrate model to study both alcoholic and non-alcoholic liver diseases in the field.