Center for Molecular Studies in Digestive and Liver Diseases (NIH/NIDDK Digestive Diseases Research Center)
The mission of our NIH-funded Digestives Diseases Research Center is to unite investigators with interests in digestive, liver and pancreatic physiology and disease in the exploration of creative experimental approaches as well as to stimulate others to enter this area of research. The scientific focus of the Center revolves around the molecular controls of cellular growth and differentiation in the digestive tract, liver and pancreas with the goal of achieving a new level of integration in biology, pathobiology, and therapy. The targeted areas of pathobiology include genetic, malignant, and inflammatory disease of the liver, pancreas and digestive tract. The Center is divided into three thematic areas:
- Developmental biology and genetics
- Microbe and host immune response
- Cell growth and differentiation
Center resources include four scientific cores to support experimental procedures for Center Investigators, a pilot project program, weekly seminar series, an annual retreat, a journal and reference library, and various enrichment programs.
Anil K. Rustgi, MD
Klaus Kaestner, Ph.D. Thomas and Evelyn Suor Butterworth
Current work in the Kaestner lab is focused on the understanding of the molecular mechanisms of transcriptional control of development, function, and proliferation of liver and intestine. Over the past ten years, his lab has shown, using genetic means, the importance of the winged helix transcription factors of the FOXA subclass to liver development and metabolism. Most recently, they discovered that sexual dimorphism of liver cancer is dependent on the Foxa factors, in which the Foxa proteins act as tumor suppressors in the female liver, but as tumor promoters in the male liver.
The Kaestner lab has also made contributions to our understanding of the molecular mechanisms of transcriptional control of gastrointestinal proliferation and differentiation. They identified the winged helix transcription factor Foxl1 as the first mesenchymal modifier of the APCmin tumor phenotype, and showed that ablation of Cdx2 causes homeotic transformation of the ileum into esophagus. Recently, his group elucidated the epigenetic control of intestinal stem cells and their descendants. Specifically, they utilized massively-parallel sequencing to determine the transcriptome and methylome of stem and differentiated cells in the mouse jejunum to elucidate dynamic changes in DNA methylation at enhancers of key regulatory genes. In addition, we his lab employed conditional gene ablation to demonstrate that maintenance DNA methylation is essential for intestinal health.
Dr. Kaestner is member of the AASLD and AGA, and has served on the NIDDK study section on “Gastrointestinal Cell and Molecular Biology”. Dr. Kaestner was Associate Editor of the Journal of Clinical Investigation, and received the Stanley Cohen Biomedical Research Award in 2011 and an NIDDK MERIT award in 2012.
|Gary D. Wu, M.D.
Ferdinand G. Weisbrod Professor in Gastroenterology
Director, Host-Microbial Analytic and Repository Core
Associate Chief of Research, Division of Gastroenterology
|Center Administrator||Kim Meyers-McCombs|
|*Please remember to cite the Center (NIH-P30-DK050306) and its core facilities (Molecular Pathology and Imaging Core, Molecular Biology/Gene Expression Core, Transgenic and Chimeric Mouse Core, and Cell Culture Core) in your publications*|