Principle Investigators

Prof. Dr. med. Erich Gulbins
Dr. Alexander Carpinteiro

Dept. of Molecular Biology,
University Hospital Essen

Prof. Dr. Erich Gulbins
Dr. Alexander Carpinteiro

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Summary

The main research focus of our group is the biomedicine of sphingolipids, in particular the role of the sphingomyelin/acid sphingomyelinase/ceramide/acid ceramidase/sphingosine pathway in bacterial infections, tumor-host interactions and cell signaling. The project within the RTG focuses on the role of acid sphingomyelinase (Asm) in the tumor response to irradiation, in particular the response of the tumor microenvironment to irradiation. The molecular mechanisms how expression of the Asm regulates radiation-resistance are presently unknown. Here, we follow two lines of investigations: 1. Tumor stem cells are protected from irradiation by the endothelial stem cell niche and that expression and activation of the Asm in endothelial cells is required to allow irradiation to destroy the stem cell niche and thereby to kill tumor stem cells. We will determine whether specific over-expression or deficiency of the Asm in endothelial cells in vitro and in vivo determines the response of the tumor and, specifically the endothelial-tumor stem cell niche to IR. Cellular effectors of Asm will be characterized after irradiation in endothelial cells in vitro, and in vivo in the tumor. We will further investigate the role of the Asm in the immune response to the tumor, in particular after irradiation of the tumor.

2. We have recently shown that the acid sphingomyelinase is critically involved in the regulation and function of regulatory T cells. We will now investigate whether the radiation-resistance of tumors in acid sphingomyelinase-deficient mice is caused by an upregulation of Tregs and, vice versa, whether overexpression of the acid sphingomyelinase can be used to radio-sensitize tumors by stimulation of immune mechanisms eliminating the tumor after irradiation.