Coordination project: Sphingolipids - Signals and Disease

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Until the late 1980s, sphingolipids were believed to be structural components of the cell membrane. However, it has now been established that sphingolipids are essential regulators of many fundamental cellular processes, such as proliferation, survival, cell death, adhesion, migration, and embryogenesis. During the first funding period, projects of the special research program 1267 focused on (i) the sorting, regulation, and cellular functions of sphingolipids and the enzymes mediating sphingolipid metabolism and (ii) the role of sphingolipids in the cardiorenovascular system (ischemic heart infarcts, atherosclerosis, coagulation, diabetic nephropathy, and fibrosis), in the immune system, in neuropsychiatric diseases (Alzheimer disease, major depression), in inflammatory and infectious diseases (sepsis, acute lung failure, cystic fibrosis, bacterial and viral infections), and in autoimmune disorders (multiple sclerosis). (iii) Several projects have already transferred insights from basic science and preclinical models into novel clinical studies, thereby proving the very successful translational aspect of the present special research program. During the second funding period of the special research program, projects will focus on translating insights from the biochemistry, biophysics, and cell biology of sphingolipids into preclinical animal models and, finally, clinical studies. Basic science projects in the special research program will investigate the topology of sphingolipids, the regulation of the primary enzymes involved in lipid sphingolipid metabolism, and the regulation and function of sphingolipid receptors. However, the focus of the special research program will be the characterization of the biomedical functions of sphingolipids in diseases of the cardiorenovascular system, the lung, the immune system and in neuropsychiatric disorders. Diseases that are studied in the special research program include coronary artery disease and arteriosclerosis, myocardial infarction, renal fibrosis, diabetic nephropathy, inflammatory diseases, autoimmune disorders such as multiple sclerosis, Alzheimer disease, major depression, mechanisms of acute lung injury, bacterial infections of the lung, cystic fibrosis, and sepsis. Animal models will serve as proof of principle and as preclinical models for developing novel treatment strategies based on the manipulation of sphingolipids in these diseases. The transfer of novel concepts about the biochemical and biological functions of sphingolipids into clinical trials will be continued. Several new clinical trials will be conducted during the second funding period; these trials will be aimed at developing novel treatments and diagnostic methods for multiple sclerosis, cystic fibrosis, cardiovascular diseases, major depression, inflammatory skin disorders, and coronary artery disease.