Header Forschung

Department of Pediatric Surgery

The research laboratory of the Department of Pediatric Surgery at the University Hospital Carl Gustav Carus Dresden is focussing on two main topics:

  • Signal transduction of the c-RET oncogene.
  • Signal transduction in normal tissue after ionizing radiation (IR).

Signal transduction of the c-RET oncogene

RET is a transmembrane tyrosine kinase that exerts its function mainly in cells of the neuronal lineage, but also in kidney and testis. Gain-of function mutants result in tumors of endocrine organs namely familial medullary thyroid carcinoma (FMTC) and multiple endocrine neoplasia Type 2 (MEN2). Loss-of function mutants result in Hirschsprungs disease, which is an intestinal obstruction due to a defective intestinal nervous system. We have detected a number of new genetic polymorphisms and mutations associated with Hirschsprungs disease. We use cell culture models of various cell types (stem cells, neural progenitor cells, neurons) with targeted mutations to understand the signal transduction cascade of c-RET. In addition we examine cell biologic functions, such as cell migration and neural outgrowth.

Signal transduction in normal tissue after ionizing radiation (IR)

IR of tumor tissue inevitably damages also normal tissue. Reduction of the normal tissue damage would increase the therapeutic range of radiation therapy. We study radiation damage in a rat model of IR-induced fibrosing alveolitis (FA). We found that the development of FA follows a stable time regime with a steady increase in nuclear factor kappaB (NF-kappaB) activity, loss of activator protein 1 (AP-1) activity after 5 weeks, infiltration of mast cells (MC) after 6 weeks and onset of FA at 8.5 weeks. In addition, we have found that heat shock protein 90ab1 (HSP90ab1) is increased in lung tissue after irradiation. We seek to identify further proteins that are likely to be involved in the pathogenesis of IR-induced FA and study them in cell culture and in-vivo models.
 

1. Okuda, K.V., et al., Duodenocolonic Fistula As A Rare Complication of Intestinal Burkitt Lymphoma in a Three-Year-Old Boy. Klin Padiatr, 2018. 230(3): p. 138-141.

2. Haase, M.G., et al., Dose-dependent histological alterations in the rat lung following intravenous application of Re-188-labeled microspheres. Int J Radiat Biol, 2013. 89(10): p. 863-9.

3. Haase, M.G., et al., Down-regulation of heat shock protein HSP90ab1 in radiation-damaged lung cells other than mast cells. J Histochem Cytochem, 2014. 62(5): p. 355-68.

4. Muller, C.M., et al., Genetic mosaicism of a frameshift mutation in the RET gene in a family with Hirschsprung disease. Gene, 2014. 541(1): p. 51-4.

5. Haase, M. and G. Fitze, HSP90AB1: Helping the good and the bad. Gene, 2016. 575(2 Pt 1): p. 171-86.

6. Laugsch, M., et al., Functional Restoration of gp91phox-Oxidase Activity by BAC Transgenesis and Gene Targeting in X-linked Chronic Granulomatous Disease iPSCs. Mol Ther, 2016. 24(4): p. 812-22.

7. Dittfeld, C., et al., Movat Pentachrom stain reveals unexpected high osteogenesis rate in aortic valves. Acta Histochem, 2017. 119(5): p. 533-537.

8. Haase, M.G., et al., GT-repeat extension in the IL11 promoter is associated with Hirschsprung's disease (HSCR). Gene, 2018. 677: p. 163-168.

9. Mayer, F., et al., Dynamics of caspase activation upon UV induced genotoxic injury. International Journal of Radiation Biology, 2020: p. 1-7.