Cellular and Molecular Pathology

Division of Cellular and Molecular Pathology

Prof. Dr. Hermann-Josef Gröne

Neurons, isolated from hippocampus. Neurons lacking GSLs show reduced dendritic processes and early pruning (right slide).
© dkfz.de

The division performs research into the cellular and molecular mechanisms underlying the rejection of malignant tumors and transplanted solid organs. Rejection reactions are regularly mounted by the organism to defend itself against tumors and include chronic fibrosing inflammation. Our goal is to get a better insight into the processes underlying tissue rejection and to transfer these findings to tumor rejection. We employ animal models of chronic inflammation and fibrosis and use rodents with inducible cell-specific deficiencies of lipids and proteins.

Two main groups of substances are studied:

1. Lipid-activated nuclear receptors and transcription factors
2. glycosphingolipids (GSL).

Recently a patent has been applied for the diagnosis of fibrosis by measurement of a “Dickkopf” protein in urine, which is involved in an important pathway of fibrosis. The Division is also involved in clinical surgical pathology and has established a reference center for renal diseases. Additionally the Division provides a consultative service for histopathology of tissue samples, including tissues from animal experiments. The Division is funded by the German Research Foundation (DFG). It is part of a concerted research activity of the DFG and receives funding by private foundations.

FUTURE OUTLOOK
1. Lipid-dependent transcription factors:
Non-steroid nuclear receptors such as liver X receptors (LXRs) and Wnt ligands have highly significant and long lasting effects on lipid carbohydrate metabolism and on the immune system. We have been able to show that activation of LXRs and inhibition of the Wnt pathway potently inhibit chronic fibrosing inflammation, mainly by an effect on parenchymal epithelial cells.

2. Sphingolipids and glycosphingolipids (GSL) are constituents of membranes of all mammalian cells.
They are expressed in a cell type- and differentiation stage-specific manner . We have demonstrated that GSL influence neuronal, metabolic and immune functions. In the brain, interactions between glycoproteins and GSL are pivotal for control of hunger and satiety and progression of degenerative diseases such as Alzheimer’s disease. GSL also influence carcinogenesis. We have shown in a cell-specific ganglioside-deficient animal that GSL are contributing to the progression of hepatocellular carcinoma. We are currently using inducible cell-specific knockouts of GSL to further define the differentiation and immune activity of GSL.

Contact

Prof. Dr. Hermann-Josef Gröne
Cellular and Molecular Pathology (G130)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 4350

Selected Publications

  • Chessa F. et al. (2016). The renal microenvironment modifies dendritic cell phenotype. Kidney Int, 89(1), 82-94.
  • Federico G. et al. (2016). Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis. JCI Insight, 1(1):e84916.
  • Nordström V. et al. (2013). Neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis. PLoS Biol. 2013;11(3):e1001506.
  • Rabionet M. et al. (2015). Male meiotic cytokinesis requires ceramide synthase 3-dependent sphingolipids with unique membrane anchors. Hum Mol Genet, 24(17), 4792-808.
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