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Organ transplantation is made possible by the introduction of drugs, that suppress the immune system (immunosuppressants). They represent the cornerstone of modern transplant medicine. However, it is difficult to determine the right medication and immunosuppressive dose in advance of the transplantation, as every patient reacts differently to the treatment. As a result, frequent complications occur, which threaten transplant outcome and the patient’s health. Recently, intestinal bacteria (the microbiome) have been suspected to impact the efficacy and toxicity of immunosuppressive drugs.

Critical Illness Polyneuropathy (CIP) and Myopathy (CIM) occur frequently as complications after severe illness where intensive care treatment was necessary. They present usually with a whole body muscle weakness which delays reconvalescence. Despite its high relevance, research is lacking regarding prognosis, course of the disease and therapy approaches. This cohort study addresses this research deficit and contributes to a better understanding of CIP/CIM and will therefore finally help to optimise care and treatment of affected patients.

The main purpose of this project is to investigate the detrimental role of a subgroup of platelets, called Reticulated platelets (RPs), in patients with coronary artery disease (CAD). RPs are young, hyper-reactive platelets with pro-thrombotic potential. High levels of RPs in peripheral blood are predictors of adverse events in different diseases including myocardial infarction. The reason of these correlations is still unclear, and the biology of RPs still has to be investigated.

Patients with chronic kidney disease (CKD) experience both thrombotic and bleeding complications. Current therapy to reduce thrombotic risk focuses on antiplatelet drugs but increases bleeding risk. This calls for novel therapies addressing CKD-specific mechanisms of thrombosis with reduced impact on bleeding. Building on our expertise in inflamed vasculature as well as thrombus formation, we believe that this can be achieved with therapies tackling a pathological endothelium-platelet crosstalk in CKD.

About 20 - 30% of humans develop nonalcoholic fatty liver disease (NAFLD) as a response to a high caloric diet. It is associated with a loss of liver function which in the worst case necessitates liver transplantation. The disease is not fully understood and no medication is available. We want to study the role of epigenetics during disease development by analysing hepatocytes from healthy and diseased donors. Epigenetics sustainably influences gene expression. It helps to define cell types and is involved in the development of various diseases.

Only a few studies exist on cognitive development across the life span of people with Down’s Syndrome (Trisomy 21). The main objective of this study is to investigate the cognitive functioning from childhood to older adult age and to examine differences to age-matched, typically developing controls. For this purpose we use neuropsychological tests, questionnaires concerning psychiatric disorders and symptoms of dementia, and magnetic resonance imaging (MRI).

Heart failure is associated with arrhythmias and sudden cardiac death. Current data indicate that noncardiac sodium channel isoforms such as Nav1.8 lead to disruptions in cardiac electrophysiology. In order to investigate the importance of Nav1.8 and to show a link between Nav1.8-induced arrhythmia development, Nav1.8 knock-outs are generated in human, induced pluripotent stem cells using CRISPR-Cas9 technology and differentiated into cardiomyocytes.

Applicants: PD Dr. sc. hum. Marco Metzger, Fraunhofer-Institut für Silicatforschung ISC, Translations-zentrum Regenerative Therapien, Würzburg
Dr. med. Frank-Mattias Schäfer, FEAPU, Abteilung für Kinderchirurgie und Kinderurologie Cnopfsche Kinderklinik, Nürnberg / Urologische und Kinderurologische Universitätsklinik des Uniklinikums Erlangen

Anal carcinoma constitutes a rare disease. Radiochemotherapy constitutes the current standard of care, but achieves only limited healing rates. So far, no clinical, molecular, or pathological parameter has been identified to adjust the given therapy to individual patients. The proposed project aims to analyze the potential of quantitative analysis of medical imaging data (“radiomics”) and artificial intelligence techniques for improved prediction of patients’ survival. The resulting image-based prediction models may be used for improved patient risk assessment in the future.

Cancer is a leading cause of death worldwide. Despite progress in therapy, new approaches to cure cancer are urgently needed. Such an approach is the topic of this project: It investigates small molecules that are completely non-toxic for cells. However, if they are activated by light, they fragment into smaller parts, which are very toxic, killing cells quickly. For activation, special light guides are needed, which precisely deliver the light to the desired spot – here, the cancer cells. Such lights are developed in this project, too.