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Applicants: Prof. Dr. Dr. med. Sabine Gabrysch , PD Dr. Volker Winkler, Prof. Dr. Dr. med. Till Bärnighausen, Dr. Andreas Deckert, Dr. med. Florian Neuhann

The quality of marginal donor grafts can be significantly improved by changing the modalities of organ preservation or by the use of techniques that allow for revitalizing of the ischemic tissue prior to transplantation. The adverse effects of extended ischemic storage times, for instance, can be alleviated by a short period of subsequent hypothermic oxygenated machine perfusion. 

DNA double strand breaks occur constantly in every cell caused by metabolic products, radiation or chemicals. Several cellular repair mechanisms are available to detect and repair DNA breaks. Genetic defects of DNA repair proteins can lead to immunodeficiency, bone marrow failure and malignancies. The only treatment option for many of these diseases is the allogeneic hematopoietic stem cell transplantation (HSCT), although associated with increased toxicity to conditioning regimens.

Certain „oncolytic“ viruses replicate selectively in cancer cells, leading to tumor lysis. This can elicit tumor vaccination effects and induce an immune response against the tumor. This effect can be enhanced by certain immunotherapies called „checkpoint antibodies“. In a clinical trial at the National Center for Tumor Diseases in Heidelberg patients with advanced colorectal and pancreatic cancer are treated with oncolytic measles vaccine viruses and a checkpoint antibody.

Our project is focused on a particular signaling pathway (HGF/Met signaling) and its influence on immunologic and metabolic changes in malignant tumors of the head and neck (oral cavity, throat, etc.). Recently, we showed that activation of a receptor (Met) results in enhanced glucose metabolism and expression of immunosuppressive proteins. Next, we intend to analyze how and to what extent immune cells are compromised by those HGF/Met-mediated changes. To this end, we use immune cells from human blood samples and determine their behavior in the presence of HGF-conditioned tumor cells.

Neuromyelitis optica spectrum disorders (NMOSD) are inflammatory disorders which mainly affect the optic nerve and the spinal cord, but can involve the brain and brainstem. The detection of antibodies (Abs) which target aquaporin-4 in a large group of NMOSD patients gave rise to the concept that NMOSD is distinct from multiple sclerosis. In addition, Abs to MOG have been found in a subgroup of patients. There is still a sizeable group of patients with clinical symptoms of NMOSD without identified specific Abs, complicating diagnosis and treatment of patients.

Clinical use of morphine, a highly-effective drug for the treatment of severe pain, is limited by rapid development of dependence and addiction after repeated or extended administration. Modifications of the μ-opioid receptor, like phosphorylation, play a crucial role in these processes. Our project investigates for the first time the main responsible enzyme GRK5 and evaluates the importance of its kinase/phosphorylation activity as compared with adapter and scaffold function.

Glioblastoma is a malignant brain tumor with poor survival. Imaging in glioblastoma, mainly performed by magnetic resonance imaging, is restricted to morphological information (tumor size, perifocal edema). Immunotherapies aim to elicit anti-tumor immune responses but monitoring treatment effects beyond the macroscopic tumor size remains difficult. Visualizing immune responses by direct tracking of effector cells could facilitate preclinical therapy development and allow treatment monitoring and patient stratification.

Aspirin exacerbated respiratory disease (AERD) is a chronic inflammatory condition characterized by asthma, nasal polyps and intolerance to aspirin and related drugs. Unfortunately, the disease mechanisms of AERD are incompletely understood and therapeutic options for affected patients are very limited. Thus, our project aims to improve the understanding of the immunological and metabolic mechanisms that cause AERD symptoms and to explore new immuneregulatory strategies for AERD therapy.