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Liver Digestive and Metabolic Disorders Laboratory

Mission Statement: The goal of the Liver Digestive and Metabolic Disorders Laboratory is to advance the art and science of medicine and biomedical research, especially as it relates to improving knowledge and care of patients with liver, digestive disease and metabolic diseases.

History of the Laboratory
This laboratory was established in 2007 shortly after the arrival of Herbert L. Bonkovsky, MD, as Vice President of Research. Throughout his professional career which now spans more than 40 years, Dr. Bonkovsky has been actively engaged in both bench research and clinical research. He continues to be active as a clinical investigator, administrator and clinician. Two key members of the laboratory moved from the University of Connecticut with Dr. Bonkovsky, namely, Drs. Hou and Mr. Tian. The group has been strengthened further by the successful recruitments of Dr. Schrum, Research Group Director, with strong interests in alcoholic liver disease and hepatic fibrogenesis, Dr. Ghosh, with expertise in cell biology and advanced microscopy, and Dr. Li, with expertise in molecular biology and virology. The group has numerous interaction with physicians and investigators throughout CMC, especially the surgical research laboratories, liver transplantation, hepato-pancreato-biliary surgery, and the core facilities for biostatistics, nucleic acids, and proteomics. The laboratories occupy approximately 900 square feet of space on the third floor of the Cannon Research Center. The labs are equifpped to carry out state-of-the-art, contemporary molecular and cell biological research. They are convenient to all of the core laboratories and facilities of Cannon Research Center, which are available for use by the staff of the laboratory whenever needs arise.

Research Summary
The laboratory's research primarily focuses upon studies of the liver in health and disease. Among Dr. Bonkovsky's longstanding interests are porphyrin heme and iron metabolism. This includes the study and amelioration of inborn and acquired disorders of metabolism, particularly the porphyrias and iron overload states. Recent work has focused upon the expression and regulation of two key enzymes in heme metabolism, namely 5-aminolevulinic acid synthase, the rate-controlling enzyme for heme synthesis, and hemeoxygenase, the rate-controlling enzyme for heme breakdown. Dr. Bonkovsky first used intravenous heme for therapy of acute porphyric attacks in 1970, and this therapy has withstood the test of time and still today is the treatment of choice for these attacks, which can be life threatening. More recently, the research team has been investigating molecular aspects of effects of heme excess and heme deficiency, especially on profiles of mRNAs and miRNAs in the liver and kidney.

We have carried out recent clinical research studies on iron uptake and homeostasis and levels of hepcidin in erythropoietic protoporphyria and on disordered circadian rhythms in acute intermittent porphyria.

There also is active study of effects of selected metallo-porphyrins, especially heme, cobalt protoporphyrin, zinc and tin meso- and protoporphyrin on hepatic heme metabolism, replication of HCV and on hepatic fibrogenesis.

Another area of active study is on effects of alcohol, iron, metallo-porphyrins and herbal remedies on hepatic fibrogenesis and hepatitis C infection. Exciting recent results indicate that the active ingredients of milk thistle (Silybum marianum) have additive or synergistic effects with certain Chinese herbal remedies to decrease the replication of the hepatitis C virus. Other work has focused on factors that regulate the uptake of HCV by hepatocytes and the influence of miRNA’s , especially the miR 29 family, on HCV replication and on the severity and progression of chronic hepatitis C.

Fatty liver disease and liver fatty acid binding protein are also areas of active interest and investigation, spear-headed by Dr. Wang and also involving Dr. de Lemos, the newest member of the faculty in Hepatology.

The laboratory also provides support for clinical studies, including the Drug-Induced Liver Injury Network and other national and local investigator-initiated studies.

Laboratory Members
Herbert L. Bonkovsky, MD
Professor of Medicine and Senior Adviser for Research
Professor of University of Connecticut
Professor of University of North Carolina

Andrew de Lemos, MD
Assistant Professor of Medicine

David Hornak, BS
Graduate Student Intern

Weihong Hou, PhD
Research Scientist

Shahin Sendi, MD, PhD
Post-doctoral Fellow

Qing Tian, BS, MS
Research Technician, I

Guqi Wang, PhD
Research Scientist

Contact Information: Weihong Hou; Guqi Wang

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