Gastroenterology, Hepatology, and Nutrition Research
The Division of Gastroenterology, Hepatology, and Nutrition currently boasts clinical and basic science research activities.
Dr. Clifford Steer, Director of Molecular Gastroenterology
Steer’s laboratory has been involved in three major areas of research during the last five years. The Sleeping Beauty (SB) transposon system functions via a cut-and-paste mechanism catalyzed by the binding of SB transposase to inverted repeats/direct repeats (IR/DRs) of the mariner transposon. It excises the relevant transgene from the transposon at the IR/DRs and inserts the element into random TA dinucleotide sites within the genome. They are applying SB as a gene therapy vector to a variety of different animal disease models, including liver, bone marrow and brain disorders. Steer's laboratory is also interested in characterizing the effects of SB transposition on genomic methylation and histone acetylation.
The second major area of research involves the use of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, as a potent antiapoptotic agent. They have used UDCA as a therapeutic agent to treat transgenic models of Huntington’s disease and retinitis pigmentosa as well as acute stroke, spinal cord injury, myocardial infarction, and acute renal failure. Steer's laboratory continues to study basic mechanisms and translational applications of UDCA. Of note, the South Korean FDA has recently approved its use for the treatment of ALS.
Steer's lab is actively characterizing the role of microRNAs in gene regulation for a number of different target organs and stem cell populations. In particular, they have identified specific microRNAs that may be involved in the progression of colon from polyp to cancer; as well as their role in the regenerating liver. The studies are both basic and translational in nature. They are also identifying specific microRNAs as biomarkers of disease that can be assayed in blood. Most notably, they have recently discovered a unique nuclear profile of mature microRNAs; and a subset of microRNAs in mitochondria that may act as a rheostat for the control of apoptosis.
The majority of the Division's funded clinical research is in the area of viral hepatitis. There are currently four funded research protocols for the management of patients with hepatitis C. Dr. John Lake is involved in clinical research studies which focus on the treatment of hepatitis C with pegylated interferon and ribavirin.
In addition, the Division is an active participant in the Midwest Hepatitis Study Group, which is a consortium of investigators interested in the management of patients with chronic viral hepatitis. Dr. John Lake is also a co-investigator on 2 NIH-funded clinical research protocols, one on the area of primary biliary cirrhosis (M. Eric Gershwin, PI) and one in the area of non-alcoholic steatohepatitis (Elizabeth Parks, PI)
The Gastroenterology Division maintains an ongoing interest in the use of TIPS (transjugular intrahepatic portal systemic shunt) for management of complications of portal hypertension.