One novel research area of great promise is the epigenetics of complex disorders, which indicates that even genes that have no disease-causing DNA polymorphisms may predispose to disease if not correctly regulated on the epigenomic level to be expressed in the appropriate amount, at the right time, or in the right compartment of the cell. Hence, our main projects are focussed on epigentic aspects of:
Chronic Pancreatitis (CP)
Our projects are dedicated to the search for epigenetic disease signatures in CP using high throughput microarray-based strategies which will help implementing a panel-based test to distinguish between CP and pancreatic cancer (PCa). Epigenetic biomarkers may prove crucial in detecting PCa early among CP patients and unaffected individuals that may me predisposed to develop PCa. Epigenetics may also help in understanding how hazardous environmental factors (e.g. diet or drugs) interact with the genome and modulate its activity.
Late onset Alzheimer's disease (LOAD)
In a previous study on LOAD, we could demonstrate that epigenetic patterns in the brain are potentially affected by an age-specific epigenetic drift that may influence age-of-onset and disease progression. By identifying differences in neuronal epigenetic profiles between healthy persons and individuals diagnosed with AD, we may be able to better understand the molecular mechanisms that drive AD pathogenesis, including the formation of amyloid plaques and neurofibrillary tangles. Our experiments have also a special focus on aging mechanisms.
Pancreatic Cancer
Our projects are especially dedicated to the study of epigenetic drift during the multi-step progression from pancreatitis to pancreatic adenocarcinomas. Pancreatic cellular epigenetic patterns are under the influence of environmental and stochastic factors and change during the course of disease and may accelerate age-and -disease-specific. Infiltrating adenocarcinoma of the pancreas is thought to develop through precursor-lesions called pancreatic intraductal neoplasias (PanINs). We are especially interested in the very early stages of PanIN formation, since aberrant DNA methylation begins presumably early, probably in pre-PanIN stages and its prevalence progressively increases during neoplastic progression even before DNA mutations occur.
The 1-Cell Methylome
The main goal of our projects is the development of innovative technologies and protocols to interrogate DNA methylation patterns (loci specific as well as whole-genome)in single mammalian cells, which would be a quantum leap in epigenetics research. At present, the study of DNA methylation in tissue samples is typically limited by mixed cell populations. The problem of cell heterogeneity has been a significant barrier to the detailed molecular analysis of normal or diseased tissue. Although much progress has been made in the field, tools to study DNA methylation in single cells are generally lacking. In collaboration with a Biotech company in Munich, we develop highly parallelized protocols using special microreation devices that could make it possible to obtain statistically relevant methylation data on single cells in a reasonable time frame.
Post Traumatic Stress Disorder (PTSD)
PTSD, is an anxiety disorder that can develop after exposure to a terrifying event or ordeal in which grave physical harm occurred or was threatened. Traumatic events that may trigger PTSD include violent personal assaults, natural or human-caused disasters, accidents, or military combat. PTSD displays biochemical changes in the brain and body that differ from other psychiatric disorders such as major depression and that suggest abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. In a collaboration with groups from the Max Planck Institute of Psychiatry in Munich, we use a PTSD mouse model to study the surprisingly strong epigenetic effects taking place in the brain of affected mice (that show behavioral abnormalities due to artificial stress factors).
Other research projects are dedicated to detailed epigenetic analyses of schizophrenia, bipolar disorder, Prader-Wiili & Angelman Syndrome, Barrett's oesophagus, colon cancer and other complex disorders.
Move over picture
Our research may lead to a better understanding of the changes in the regulation of genes and genomes that occur in complex diseases. It may also aid in understanding why the same gene sequence may predispose an individual to disease and in other cases does not, and elucidate the molecular mechanisms of how hazardous environmental factors interact with the genome. Results from the work may lead to new diagnostics and effective therapies. However, prior to a therapeutic intervention, identifying and understanding the epigenetic code is a necessity.
