Disease Mechanisms & Targets

This research programme focuses on the analysis of molecular mechanisms involved in the development of various diseases, such as cardiovascular diseases. The diseases have multi-factorial causes; genetic constellations play a role, as do environmental and nutritional influences. Because they progress differently in different patients, they respond differently to treatments. Researchers at ISAS are identifying potential target molecules in order to gain a comprehensive understanding of the pathomechanisms and facilitate earlier diagnosis of the diseases in the future, with fewer side effects and better individual therapy. 

In their basic research, the scientists use methods that are by no means limited to the genome level, but also include proteomic and metabolomic parameters. The researchers use multi-omics techniques for this purpose and test and optimise them. One focus in the »Disease Mechanisms & Targets« programme is on cardiovascular diseases. The institute can draw on many years of analytical expertise in this field, including extensive studies of the platelet proteome and the detailed elucidation of platelet dysfunction and molecular processes involved in heart failure (cardiac insufficiency).  

Molecular mechanisms of heart failure

The molecular causes and the progression of the disease are still largely unknown for many diseases of the cardiovascular system. In the »Disease Mechanisms & Targets« research programme, the scientists are working on improving the diagnosis of heart failure and establishing new therapeutic approaches. They are combining classical methods of molecular genetics and biochemistry with high-throughput methods. The researchers at ISAS cover the entire spectrum of analysis, from the detailed investigation of individual components to the examination of entire cellular systems.

Characteristic disease progression & reduction of side effects

The scientists are developing new diagnostic and therapeutic tools for the differentiation of several heart diseases. To do this, they work with transgenic mice. The aim is to identify spectroscopic characteristics of different disease processes. The research group is also developing and optimising silicon-based nanocontainers that enable the myocardial-cell-specific application of medications and thereby a reduction in side effects.

Healing processes in the heart through CAP 

The researchers are investigating the mechanisms of cold atmospheric plasma (CAP) in the treatment of cardiovascular diseases. Up to now, plasmas such as these have been tested primarily in the fields of tissue repair, the treatment of infectious skin diseases, dentistry and cancer treatment. They could increase the concentration of nitrite in the blood and thus reduce a cardiovascular risk factor.

Imaging techniques

In 2021, the scientists strongly advanced biospectroscopic analyses using imaging vibrational microscopy and high-resolution microscopy. Using optical methods, they succeeded in investigating the various molecular mechanisms of heart failure and diagnosing the corresponding diseases in their early stages. In cooperation with the Julius-Maximilians-Universität of Würzburg and the University of Duisburg-Essen, the scientists investigated various mouse models with genetic diseases.

In 2021, in order to fully assess the potential of non-linear spectroscopic imaging instrument and various assays for the identification of cardiac involvement in metabolic disorders and genetic storage diseases such as Fabry disease, the researchers for the first time used the coherent anti-stokes raman scattering (CARS) microscopy to investigate a mouse model. The analysis method proved to be precise. Thanks to the high sensitivity of the spectral information obtained and computer-aided diagnosis, subtle changes in protein lipid changes in the protein-lipid content between heart tissue in Fabry disease and control tissue could be reliably detected by up to 96 percent. Diagnosis by means of CARS microscopy thus has the potential to support gold-standard histology and other diagnostic methods for detecting the involvement of specific organs in Fabry disease. 

 

Prof. Dr. Kristina Lorenz

Programme Coordinator