Kowdley Laboratory

The focus of the research in our group is in the area of genetic and metabolic liver diseases. We have been studying the role of hepatic iron overload and mutations in the hemochromatosis (HFE) gene in hereditary hemochromatosis, chronic viral hepatitis, nonalcoholic steatohepatitis and end-stage cirrhosis.

In the area of hemochromatosis, we are characterizing the phenotypic features associated with mutations in other genes involved in iron transport, such as transferrin-receptor 2, HAMP and hemojuvelin. Our translational research program is aimed at understanding the relationship between duodenal expression of genes involved in iron transport and expression of the hemochromatosis phenotype among individuals homozygous for HFE mutations using RT-PCR and microarray techniques and in understanding factors regulating iron absorption in humans and murine models of hemochromatosis.

In the area of end-stage cirrhosis, we are examining the effect of hepatic iron overload on long-term outcomes after liver transplantation via multicenter cohort and population-based studies.
Another major research interest is nonalcoholic steatohepatitis (NASH), an increasingly prevalent liver disease. We are examining the contribution of body iron stores and HFE mutations to insulin resistance, oxidative stress and liver injury in this disease via cross-sectional studies and prospective trials of iron depletion.

Our laboratory work is directed towards understanding the etiology of NASH. Currently we are investigating effects of free fatty acids and iron overload on the redox status and insulin sensitivity of cultured hepatocytes. Our plans for parallel work in a model of NASH will allow us to also examine the role of the immune system and other liver cell types in the progression of this disease.

We are actively evaluating several new therapies for patients with chronic liver disease including ursodeoxycholic acid for primary sclerosing cholangitis (funded by an RO-1 grant), a cholestatic liver disease with autoimmue features and several therapies for NASH including vitamin E, pioglitazone, omega-3 fatty acid and iron depletion. We are one of eight clinical centers in the NIDDK-funded Nonalcoholic Steatohepatitis Clinical Research Network (funded by a UO-1). In addition, we have an R21 grant to develop and study a novel susceptometer for noninvasive measurement of liver iron concentration.

Dr. Kris Kowdley is the Director of the Liver Center of Excellence at Virginia Mason Medical Center and Clinical Professor of Medicine at the University of Washington. Dr. Kowdley received his BS in Biology and Anthropology as a member of the Dean's List at Columbia University, and his medical degree from Mount Sinai School of Medicine. He completed his internship and residency at Oregon Health Science University and a Fellowship in Gastroenterology and Hepatology at Tufts University School of Medicine. Dr. Kowdley has presented his research in liver diseases at more than 100 national and international medical centers and scientific symposia. He is the author of over 300 articles, book chapters, reviews and commentaries in this area and has been published in the New England Journal of Medicine, Annals of Internal Medicine, Hepatology, Gastroenterology, Archives of Surgery, Journal of Clinical Gastroenterology and among other professional publications.

Dr. Jim Nelson has a PhD in Molecular Biology/Genetics and completed a post-doctorate fellowship in liver directed gene therapy at the UW and Stanford. Laboratory interests include investigating the effect of iron on glucose and lipid metabolism in murine models of NASH and the role of oxidative stress in NASH disease progression. Several years ago he developed an interest in clinical research and completed the Clinical Trials Certificate Program, at the University of Washington. Since that time he has designed and coordinated multiple investigator-initiated clinical trials for the treatment of NASH. He is currently a staff scientist/research coordinator at BRI.

Dr. Don Messner earned a PhD in Pharmacology at the University of Washington and a postdoctoral fellowship at Washington University at St. Louis in the Department of Medicine. He is currently a Staff Scientist at BRI and an Associate Research Scientist at Bastyr University. His research on iron-related liver diseases includes an interest in biologically based practices of Complementary and Alternative Medicine.

Dr. Heather Klintworth has a PhD in Toxicology from the University of Washington and is currently a postdoctoral research associate at BRI. She is developing in vitro models to study the effects of iron on different hepatic cell types from a mechanistic perspective. Her research aims to determine the role of iron in the activation of hepatic macrophages and stellate cells and how this may lead to the progression of NASH. She plans to further investigate her findings using in vivo models and translational studies in humans.

Dr. Yu Li earned his PhD in Microbiology at the University of Washington.  Using quantitative genomic approaches, he mapped out virus-host interactions during the infections of HCV and AIDS viruses. As a postdoctoral fellow at the University of Washington, he spearheaded the use of array technologies for the study of cellular microRNAs and their contribution to the lethality of the 1918 pandemic influenza and highly pathogenic H5N1 avian influenza viruses.  At BRI, Dr. Li is currently focusing on the application of high-throughput genomics, bioinformatics and molecular biology approaches to 1) identify serum microRNAs as early disease indicators for serious liver diseases including non-alcoholic steatohepatitis and hepatocellular carcinoma; 2) modulate microRNA activities in cell-based assays and evaluate their potential as therapeutic targets.