Specialization
Anatomy, Molecular biology, Nutrition, Liver
Focus of research
Proteins turn over continuously. Protein breakdown generates toxic ammonia. Glutamine and urea synthesis are the main pathways for ammonia detoxification, but their mutual dependence is still not sorted out. A ~5% reduction in urea synthesis causes lethal hyperammonemia, but a 35% reduction in glutamine synthesis produces no phenotype, even though glutamine synthetase is, thus far, held responsible for preventing hyperammonemia. Using tissue-specific knockout mice and stable isotope-based fluxomics, we investigate the interorgan dependence and (patho )physiological determinants of glutamine and urea synthesis, and the requirement of glutamine synthesis for urea synthesis. Environmental conditions that are studied include high-protein diets (high-protein diets are satiating and facilitate weight reduction), fasting (a proxy for cachexia), and intestinal bacterial overgrowth and acidosis (the encephalopathy-provoking condition in cirrhotic patients).
The pelvic floor is the last underexplored area in human anatomy, even though it plays a key role in deliveries and accounts for incontinence in one-third of our female postmenopausal population. Because classical dissection has proven an inadequate research tool and the correspondence between radiological and anatomical details remains largely incomplete in this region, we employ ultra-large sections and immunohistochemistry of fetal and adult specimens as tools to assemble annotated three-dimensional maps of the pelvic floor.