Prof. Dr. Dr. Wilhelm Stoffel

Principal Investigator CECAD Cologne


Prof. Dr. Dr. Wilhelm Stoffel
Principal Investigator, CECAD Cologne
 +49 221 478 6881

Zentrum für Molekulare Medizin Köln
Uniklinik Köln
Joseph-Stelzmann-Str. 52
50931 Köln

Prof. Dr. Dr. Stoffel´s group studies the biochemical and cellular structure-function relationship of complex phospho-(PL) and sphingolipids (SL) in mammalian cell membranes, preferentially in targeted genetically mouse models, which are mimicries of human diseases. Their goal is to understand the molecular impact of the key role of sphingomyelin (SM) metabolism in these mouse mutants, which develop systemic (hypothalamus-pituitary-growth-axis) and cartilage-bone derived juvenile dwarfism and chondrodysplasia, a basis for future novel therapeutic approaches.

Our research: SL, PL and cholesterol form the complex architecture of all mammalian membranes. Stoffel´s group investigates in the current research project the structure-function relationship and the metabolism of SL and their impact on cellular functions. They focus on the regulation of biochemical and cellular processes by Sphingomyelin-Phospho-Diesterase 3 (SMPD3) and its catabolites. The SMPD3-deficient mouse represents a novel form of juvenile systemic hypoplasia (dwarfism) combined with chondrodysplasia.

Our successes: Mouse mutants were generated to unravel the in vivo functions of SL. In the current project, they pinpointed 1. the subcellular localization in the Golgi cisternae, 2. the pivotal role of SMPD3 and SM catabolites in Golgi vesicular protein transport and protein secretion. 3. Lack of SMPD3 in hypothalamic neurosecretory neurons and chondrocytes leads to endoplasmatic reticulum (ER)-protein storage, ER-stress and apoptosis. These results provide crucial insight into the molecular pathobiochemistry of dwarfism combined with chondrodysplasia.

Our goals: The focus of the group is directed towards understanding the molecular basis of hitherto unrecognized functions of SL in the regulation of growth of mouse and man. This research aimed at generating the molecular platform for new therapeutic approaches in the treatment of impaired growth during adolescence. Other rapidly growing cell types will be included in the concept.

Our methods/techniques: The group utilizes lipidomic analysis, genetics, biochemical, cell biological and imaging methods.


Figure 1: Immunhistochemistry unveils disrupted Golgi vesicular protein transport and secretion of extracellular matrix protein (ECM) in smpd3-/- chondrocytes compared to collagen 2A network in ECM.

Figure 2: Sagittal section of pituitary gland. SMPD3 deficiency causes hypothalamus-induced combined pituitary hormone deficiency on the basis of systemic hypoplasia.

Figure 3: X-ray image of pelvis and hind limb long bone of control (+/+) and smpd3 -/- mouse.

CECAD Cooperations
EXTERNAL Cooperations
  • Prof. Dr. H. Abken, Center of Molecular Medicine, Clinic for Medicine I, Cologne, DE
  • PD Dr. M. Odenthal, Institute for Pathology, Cologne, DE
  • Prof. Dr. M. Thevis, Institute for Biochemistry, German Sport University Cologne, Cologne, DE