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Research Group Lipid Pathobiochemistry

PD Dr. Roger Sandhoff

Within our research group Lipid Pathobiochemistry we investigate the endogenous and pathological functions of sphingolipids. Sphingolipids are a complex class of membrane lipids (ceramides, cerebrosides, sphingomyelins, complex glycosphingolipids, gangliosides, and sulfatides), but contain also some important extra ad intracellular signaling molecules, such as sphingosine 1-phosphate. They are derived by combinatorial biochemistry at the membranes of the endoplasmic reticulum and Golgi apparatus of the cells. Transported to the plasma membrane they may be further modulated. The cell intrinsic expression of various enzymes generates cell-specific sphingolipid patterns, which depend on cell differentiation, cell activation, but also cell transformation, e.g. to cancer cells. The ganglioside GD2, a glycosphingolipid, for example is expressed quite selectively on various tumor cells and is prominent in neuroblastoma. Sphingolipids in turn modulate cellular processes like proliferation, type of differentiation or activation, and can also influence the potential of tumor cells to metastasize. Although present in all cells of the organism, sphingolipids can have quite different functions. Cerebrosides and sulfatides contribute to the structure of myelin sheaths whereas special ceramides are essential for a functional lipid based skin barrier, a barrier that allows us to live on land. Specific gangliosides on the surface of axons interact with lectins of the surrounding myelin sheaths and stabilize by that the membrane-membrane interaction. Other glycosphingolipids are essential for the structure of intercellular bridges between maturating spermatids of a clone. Within cell membranes, sphingolipids like gangliosides can also interact with cell membrane proteins including signaling receptors, by that modulating their signaling activity. Or they support endocytosis by that regulating the internalization of membrane bound receptors or the uptake of compounds from the extracellular space.

To determine the specific composition of sphingolipids in various cell types or tissues, we have developed chromatographic and mass spectrometric-based methods in our lab.

The opportunistic pathogen C. albicans (purple colorized) penetrates the ceramid-deficient skin barrier (to the right) of the skin biopsy. R. Jennemann et al. 2012 Human Molecular Genetics
© Human Molecular Genetics

Selected Literature

  1. Pilz, R., L. Opálka, A. Majcher, E. Grimm, L. Van Maldergem, S. Mihalceanu, K. Schäkel, A. Enk, F. Aubin, A.-C. Bursztejn, E. Brischoux-Boucher, J. Fischer, and R. Sandhoff. 2021. Formation of keto-type ceramides in palmoplantar keratoderma based on biallelic KDSR mutations in patients. Human Molecular Genetics.
  2. Jennemann, R., M. Volz, F. Bestvater, C. Schmidt, K. Richter, S. Kaden, J. Müthing, H. J. Gröne, and R. Sandhoff. 2021. Blockade of Glycosphingolipid Synthesis Inhibits Cell Cycle and Spheroid Growth of Colon Cancer Cells In Vitro and Experimental Colon Cancer Incidence In Vivo. Int J Mol Sci 22.
  3. von Gerichten, J., D. Lamprecht, L. Opalka, D. Soulard, C. Marsching, R. Pilz, V. Sencio, S. Herzer, B. Galy, V. Nordstrom, C. Hopf, H. J. Grone, F. Trottein, and R. Sandhoff. 2019. Bacterial immunogenic alpha-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation. J Lipid Res 60: 1892-1904.
  4. Rabionet, M., A. Bayerle, R. Jennemann, H. Heid, J. Fuchser, C. Marsching, S. Porubsky, C. Bolenz, F. Guillou, H. J. Grone, K. Gorgas, and R. Sandhoff. 2015. Male meiotic cytokinesis requires ceramide synthase 3-dependent sphingolipids with unique membrane anchors. Hum Mol Genet 24: 4792-4808.

 

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