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 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.
In addition to our laboratory-based basic and translational research program, the Liver Center of Excellence has an active portfolio of clinical investigation and clinical trials in various chronic liver diseases. Dr. Kowdley is a principal investigator on the NIH-funded Nonalcoholic Steatohepatitis Clinical Research Network and on the NIH-funded Hepatitis B Research Network, both funded via the U0-1 mechanism and in two studies of biomarker discovery in primary sclerosing cholangitis and hemochromatosis. Dr. Kowdley and colleagues are also investigators in a large number of industry-funded pharmacotherapeutic trials in the area of hepatitis C, nonalcoholic steatohepatitis, primary biliary cirrhosis and primary sclerosing cholangitis.
Kowdley Laboratory Members
Dr. Kris Kowdley is the Director of the Liver Center of Excellence at Virginia Mason Medical Center, Clinical Professor of Medicine at the University of Washington, and a Clinical Investigator at BRI. 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 125 national and international medical centers and scientific symposia. He is the author of over 325 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. Priya Handa has a PhD in Biochemistry from Indian Institute of Science, Bangalore, India. During her postdoctoral work in University of Washington (UW)Hematology, she studied inflammatory and apoptotic signaling pathways. As a research scientist in UW Cardiology, she uncovered the effect of nitric-oxide signaling on adipose tissue inflammation and obesity; and the protective role of ApoA-I/HDL in mitigating saturated fat-induced inflammation. In the Kowdley Laboratory, Dr. Handa aims to 1) study the pathogenic role of immune mediators in the progression of non-alcoholic fatty liver diseases by using in vivo models and in vitro cell culture systems from a mechanistic perspective, and 2) decipher the mechanism of iron induced activation of hepatocytes, hepatic macrophages and stellate cells and how this may lead to the etiology of nonalcoholic steatohepatitis (NASH) and extend her findings to translational studies in humans. In addition, she would like to study the mechanistic link between vitamin D depletion and NASH.
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.
Vicki Morgan-Stevenson joined the Kowdley lab in 2012. Previously she worked for Drs. John Harlan and Bob Winn in the Department of Surgery at Harborview Medical Center. She earned her BS in Molecular Biology from the University of Washington. At BRI she is currently studying the effects of iron in liver disease.
Dr. Jim Nelson has a PhD in Molecular Biology/Genetics and completed a post-doctorate fellowship in liver directed gene therapy at the University of Washington and Stanford University. 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 Research Assistant Member at BRI.
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. He is currently a staff scientist at BRI.