Hans Fischer Senior Fellow
MicroRNAs Regulating Diabetes and Obesity
Prof. Klaus H. Kästner, Ph.D., M.S., was born on April 26, 1961 in Münster, Germany. After studying biology and chemistry at the University of Bremen, he went to the University of Maryland in College Park, MD, on a DAAD scholarship, where he received his Master of Science (M.S.) degree in 1986. He then enrolled in the Biochemistry, Cell and Molecular Biology doctoral program at the Johns Hopkins University Medical School in Baltimore, MD, where he obtained his Ph.D. in 1990. He then moved to Heidelberg, Germany for a postdoctoral fellowship under Professor Günther Schütz at the German Cancer Research Center. He was appointed Assistant Professor in the Department of Genetics at the University of Pennsylvania Perelman School of Medicine in1997, was promoted to Associate Professor in 2002 and full Professor in 2006. Since 2006, his is the endowed Suor Butterworth Chair of Genetics in the Department of Genetics at the University of Pennsylvania.
Klaus Kästner’s work is focused on the understanding of the molecular mechanisms of beta-cell mass expansion and glucose homeostasis. In addition, his laboratory has pioneered the development of functional genomics tools applicable to the study of the endocrine pancreas. Klaus Kästner was a founding member of the NIDDK-sponsored Beta Cell Biology Consortium, a group of 30 investigators whose common goal is to understand the developmental biology and molecular physiology of the pancreatic beta-cell in order to allow for improved cell-replacement therapy of type 1 diabetes. He is also a founding member of the recently formed, NIH-supported Human Islet Research Network (HIRN).
Klaus Kästner has served on multiple review panels for the Juvenile Diabetes Research Foundation and for the National Institute for Diabetes, Digestive and Kidney Diseases. He was member of the Trans-NIDDK Strategic Planning Group on Genetics, Genomics, and Bioinformatics in 2000. Dr. Kästner serves on the editorial boards of Diabetes and Molecular Endocrinology, and is Associate Editor of the Journal of Clinical Investigation. He has co-authored more than 250 publication in the areas of beta-cell function, glucose homeostasis, and organ development.
2012 NIH MERIT Award
2011 Stanley N. Cohen Biomedical Research Award
2000 R. Robert and Sally D. Funderburg Research Scholar Award
Pancreatic insulin-producing beta-cells play a key role in diabetes pathology. Klaus Kästner led functional genomics efforts in the field, first identifying thousands of transcripts expressed in the pancreatic islet, and later by defining key chromatin marks of human alpha- and beta-cells. Recently, he found that the imprinted MEG3 locus on human chromosome 14, encoding 54 microRNAs, is dysregulated in human diabetic beta-cells, and showed that this correlated with increased DNA methylation at the locus. He also pioneered the genetic analysis of the FoxA family of winged helix transcription factors, which play key roles in the organogenesis and function of liver, pancreas, and gut. In fact, without the FoxA factors, neither liver nor pancreas can form during development. In adult physiology, Klaus Kästner showed that the FoxA genes are central regulators of alpha and beta-cell function, and the transcriptional response to fasting in the liver. In addition, he discovered that the well-known sexual dimorphism of risk for liver cancer – where men are three-fold more likely to be affected than women – is dependent on the FoxA proteins enabling binding of the androgen and estrogen receptors to key targets in the male or female liver, respectively. This finding is relevant to human disease, as SNPs in FOXA binding sites affect occupancy of the FOXA proteins and the sex hormone receptor in human liver.
- The diabetes gene Hhex maintains -cell differentiation and islet function. Genes & Development 28 (8), 2014, 829-834 more… BibTeX Full text ( DOI )
- Epigenetic Regulation of the DLK1-MEG3 MicroRNA Cluster in Human Type 2 Diabetic Islets. Cell Metabolism 19 (1), 2014, 135-145 more… BibTeX Full text ( DOI )
- Epigenomic plasticity enables human pancreatic α to β cell reprogramming. Journal of Clinical Investigation 123 (3), 2013, 1275-1284 more… BibTeX Full text ( DOI )
- Foxa2 and H2A.Z Mediate Nucleosome Depletion during Embryonic Stem Cell Differentiation. Cell 151 (7), 2012, 1608-1616 more… BibTeX Full text ( DOI )
- Foxa1 and Foxa2 Are Essential for Sexual Dimorphism in Liver Cancer. Cell 148 (1-2), 2012, 72-83 more… BibTeX Full text ( DOI )
- Cdx2 regulates endo-lysosomal function and epithelial cell polarity. Genes & Development 24 (12), 2010, 1295-1305 more… BibTeX Full text ( DOI )
- Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development. Genes & Development 22 (24), 2008, 3435-3448 more… BibTeX Full text ( DOI )
- Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress. Nature Medicine 14 (8), 2008, 828-836 more… BibTeX Full text ( DOI )
- Foxa2 Controls Vesicle Docking and Insulin Secretion in Mature β Cells. Cell Metabolism 6 (4), 2007, 267-279 more… BibTeX Full text ( DOI )
- Expansion of adult beta-cell mass in response to increased metabolic demand is dependent on HNF-4 . Genes & Development 21 (7), 2007, 756-769 more… BibTeX Full text ( DOI )
- Foxa2 integrates the transcriptional response of the hepatocyte to fasting. Cell Metabolism 2 (2), 2005, 141-148 more… BibTeX Full text ( DOI )
- The initiation of liver development is dependent on Foxa transcription factors. Nature 435 (7044), 2005, 944-947 more… BibTeX Full text ( DOI )