Benutzerspezifische Werkzeuge

Hampe lab

Hampe lab

more information on CRTD website

Research focus

Genomic and molecular disease mechanisms of gastrointestinal and hepatological disorders (Group leader: Prof. Jochen Hampe, MD)

The research interest in our group is to unravel the molecular pathways that are implicated in the development of gastrointestinal and hepatological disorders. Specifically, our research focuses on systematic, genome-wide approaches in patient material derived from individuals with disorders such as nonalcoholic liver disease, alcoholic liver disease, gallstone disease, inflammatory bowel disease (IBD), diverticulitis and diverticulosis, colorectal cancer, gallbladder and hepatocellular cancer.

GENOME-WIDE ASSOCIATION STUDIES

Studies of genetic risk factors of complex disorders, and specifically, genome-wide association studies (GWAS) have been widely employed in the study of complex disorders. Through close cooperation with German and international hospitals and research centers we have actively recruited large cohorts with complex disorders and use these for the identification of novel susceptibility genes for gallstone disease, alcoholic liver cirrhosis, colonic diverticular disease (diverticulosis, diverticulitis), colorectal cancer, hemochromatosis,  inflammatory bowel disease and sarcoidosis.

For instance, our group has identified the first common risk factor for gallstone disease (ABCG5/8) through a genome-wide association study. This is now the most widely replicated human susceptibility gene for gallstone disease, which has been shown to confer an approximately twofold increase in gallstone risk. This gene codes for a heterodimeric biliary cholesterol transporter. In order to better understand the mechanistic disease effect conferred by ABCG5/8, genetic fine mapping and cellular assays established cholesterol hypersecretion caused by ABCG8-Asp19His amino acid change as the disease causing mechanisms in this disorder. Recently, our group lead the first genome-wide association study in alcoholic liver cirrhosis.

EPIGENETICS OF GI DISORDERS

Epigenetics describes heritable changes in gene expression without changing the DNA-sequence. To date three mechanisms are known to induce epigenetic changes: DNA methylation, histone modification and ncRNA associated gene silencing.

In our group, we focus on changes in DNA methylation in fatty liver disease where we were able to identify NAFLD-specific expression and methylation differences for nine genes coding for key enzymes in intermediate metabolism and insulin/insulin-like signaling. Intra-individual comparison of liver biopsies before and after bariatric surgery showed NAFLD-associated methylation changes to be partially reversible. Postbariatric and NAFLD-specific methylation signatures were clearly distinct both in gene ontology and transcription factor binding site analyses.

We are now extending the analysis to the key transcription factors to identify differentially expressed genes by Chip-Seq analysis and FAIRE-Seq.

DYSREGULATION OF TRANSLATION IN COMPLEX DISEASES

Eukaryotic protein synthesis involves three stages, initiation, elongation and termination, in which initiation is the rate-limiting step. The complex nature and the number of different factors involved in the translation initiation process harbours several mechanisms how protein synthesis can be controlled. These mechanisms can be divided in to two broad categories:

  1. Global up- or downregulation of protein synthesis by changing the phosphorylation state or degradation of initiation factors and
  2. regulation of individual transcripts through the activity of cis-acting elements, like internal ribosomal entry sites (IRES), sequence specific RNA binding proteins, secondary structures influencing scanning kinetics, miRNAs and upstream open reading frames.

We use ribosomal profiling, a method which allows a transcriptome-wide mapping of ribosomes with sub-codon resolution to analyze the complex nature of translational dysregulation in metabolic diseases i.e. non-alcoholic fatty liver disease and different cancer entities.

Team

Scientists

Mario Brosch, PhD

Lab head

Functional genomics

Tel.: +49 (0) 351 458 4683

Alexander Herrmann

Bioinformatics

Tel.: +49 (0) 351 458 4146

Stephan Buch, PhD

Genetic association studies

Tel.: +49 (0) 351 458 4684

Veera Raghavan Thangapandi

Tel.: +49 (0) 351 458 4684

Vincent Moser

Sophie Nehring

PhD students
Tohid Siddiqui
Technical team

Luise Obermann

Tel.: +49 (0) 351 458 3757

Sylvia Lehmann

Tel.: +49 (0) 351 458 3757

Publications

Please find our current publication activity @Google Scholar (link: https://scholar.google.de/citations?user=u9TRfVoAAAAJ&hl=de&oi=ao) and pubmed (link: https://www.ncbi.nlm.nih.gov/pubmed/?term=hampe-j)