Sebastian Mueller, MD, PhD

 

Professor of Medicine,

Department of Medicine, 

Salem Medical Center

University of Heidelberg

 

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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.

Translational Research

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 mechenisms 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. 

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.  

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