Human life starts with the fusion of oocyte and sperm, a process that happens in the oviduct of the mother. During the subsequent cell divisions the developing embryo migrates through the oviduct before it implants in the uterus between day 5 and 6. Migration and division of the embryo have to be precisely coordinated and regulated; otherwise tubal pregnancy or loss of the embryo might result.
The targeted drug inhibitor everolimus is one of the few approved therapies for advanced neuroendocrine tumors (NETs), a common type of gut cancer. However, most patients develop a resistance after less than one year. In this project we will investigate the mechanisms of everolimus resistance in two human pancreatic NET cell lines showing stable resistance to everolimus and in an everolimus-resistant tumor grafted in to mice. We will also explore whether the new drug BYL719 can overcame everolimus resistance, as we have already shown in cell lines.
Human cells can remove themselves when they become a danger for neighboring cells or even the entire organisms by a program, termed apoptosis. In healthy human beings, apoptosis contains infections and severe diseases, such as cancer. The development of a tumor requires misregulation of apoptosis. Among other characteristic properties, tumor cells often show an altered metabolism of the sugar glucose. We have preliminary evidence for the involvement of the enzymes funneling glucose into the metabolism, so called hexokinases, being involved in the inhibition of apoptosis.
Body dysmorphic disorder (BDD) is a relatively common and serious mental disorder in adolescents. However, waitlists for treatment are long and barriers (e. g., shame) to seek treatment are high. On the other side, affinity of adolescents to electronic media might increase accessibility. Therefore, the effectiveness of a 12-week guided online intervention consisting of six cognitive behavioral treatment modules is tested against a psychoeducation and weekly disorder-unspecific therapist contact in 15 to 21-year old individuals with BDD.
Severely calcified coronary stenoses provide a peculiar challenge for the interventional treatment in the cathlab. Before implanting a coronary stent, it is essentially necessary to achieve a sufficient lumen gain. If a stent cannot be deployed completely due to severe calcifications, this is a major reason for restenosis during further course.
The present project aims at closing decisive gaps in our pathophysiological understanding of sleep disordered breathing in patients with (precapillary) pulmonary hypertension and in patients with systolic heart failure. In these groups of patients the immediate effects of established nocturnal mask based therapies on not only respiratory (sleep disordered breathing related) parameters but also on cardiac and autonomic nervous system function parameters will also be investigated critically.
Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive embryonal brain tumors. In one distinct subgroup of AT/RT, the sonic-hedgehog (SHH), the signaling pathway is activated downstream of the trans membranous receptors. We recently discovered that arsenic trioxide (ATO) inhibits the SHH-signaling downstream which made ATO therapeutically interesting. Even though ATO has been successfully introduced into clinical treatment of leukemia, numerous clinical trials in solid tumors failed due to insufficient drug concentrations in the tumor tissue.
Accumulating evidence has shown that gut-microbiota related metabolites may contribute to the development of cardiovascular diseases. Endothelial lesions and dysfunction are early vascular hallmarks in the development of atherosclerotic heart disease. Within the funded project we aim at evaluating the impact of distinct gut-microbiota related metabolites on regeneration and repair mechanisms of endothelial cells in arterial vessels after injury.
Parkinson’s disease (PD) is characterized by locomotion difficulties, affecting mostly elderly people. While the cause is mostly unknown, mitochondria, the powerhouse of the cell, are often affected, resulting in a deficit of cellular energy that is required for locomotion. Recently, awareness is given to the importance of different fats in efficient functioning mitochondria. In this project, we want to identify changes in fat and investigate its effect on mitochondrial function in PD. Ceramide is one type of fat that is changed in PD and is crucial for mitochondrial and brain function.
Hereditary cone-rod dystrophies (CRDs) are rare diseases of the human eye (1:40,000) that lead to sensitivity to light, colour blindness, reduced visual acuity and sensitivity, progressive loss of vision and night blindness. We investigate the molecular basis of CRDs resulting from mutations of two visual transduction proteins, using cell biological, biophysical and structural biology methods. Among other things, we will produce so-called "nanobodies", unique antibodies against the two proteins, to find out how the mutations limit the functionality of these proteins.
