Sebastian Mueller, MD, PhD
Professor of Medicine,
CAR, University of Heidelberg
VISCERA AG Bauchmedizin Bern
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Sebastian Mueller, MD, PhD
Professor of Medicine, CAR, University of Heidelberg
VISCERA AG Bauchmedizin Bern
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Our
group has a long term interest both in basic science projects and translational
projects directly linked to human diseases, namely liver
diseases. Major focus is the cellular function of oxygen derived molecules (so called
ROS-reactive oxygen species) e.g. in signal transduction. Some findings
from our research activities are
presented at a glance by clicking on the left tool bars Biochemistry,
Cell
biology and Clinical studies. Among many publications in peer-reviewed journals, major findings of our work are summarized in a book published in 2023 by Springer Nature entitiled "Alcohol and alcohol-related diseases" .
A
major goal is to better understand molecular mechanisms of liver diseases
and their consequences such as cancer in
order to develop diagnostic tools to early recognize these diseases and to identify novel therapeutic
approaches. One major expertise is the non-invasive
detection and monitoring of chronic liver diseases. Thus, we have developed refined algorithms to accurately
diagnose liver cirrhosis which is is a common liver disease (up to 7% in the
general population) and the end-stage of most chronic liver diseases. We also
engage in various studies that focus on the genetic factors that modify the
development of liver diseases. A better understanding of the molecular mechanisms of alcoholic but also non-alcoholic liver disease (ALD and NALD) is another major focus at the Center for Alcohol Research. Alcoholic liver disease is the most common liver disease. Since alcohol consumption has been rather stable over decades or is even drastically increasing in several parts of the world, we think that an early detection of individuals with high genetic risk for developing severe liver disease is an important alternative strategy to combat the detrimental consequences. In addition, elucidation of key mechanisms of ALD could help in developing novel targeted therapeutic approaches. For instance, a majority of patients with ALD show increased iron overload in their livers, a condition known to cause cancer. In later cirrhotic stages, iron further increases even after stopping drinking. If the basic mechanisms of this iron overload would be understood, novel therapeutic concepts could be developed. Finally, we hope to learn a lot from our long-term prospective follow-up study performed from 2007-2022 that also also contains mortality data in heavy drinkers.
Basic Research Reactive oxygen species
(ROS) are involved in the pathology of many diseases. The research on ROS has been
drastically limited because these small molecules are very short-lived and
hardly to detect in human tissues. The development of novel assays
(e.g. for H2O2) has
allowed us the real-time assessment of this central ROS at ultra-low
concentrations. Based on this assay,
our group has also been pioneering in developing novel in vitro models to
study in detail cellular functions of ROS in human cells. As
a major achievement, we have been recently able to simulate the oxygen and
peroxide environment in cultured cells that typically occur in humans during inflammation, cancer but also under many physiological
conditions. These models have helped us to better understand cellular functions of
ROS including cellular metabolism of ROS (how they are produced and
metabolized) as well as how ROS engage in the intracellular and intercellular
communication (redox regulation) e.g. in iron
metabolism. |
