Distinct human and murine in vitro cellular differentiation models that represent different germ layers are used within the RTG 2578 in order to analyse the response of individual stem- and progenitor cells to model-relevant genotoxic agents. The implementation of various test systems and well-defined genotoxins together with an extensive analysis of relevant end points will foster multidisciplinary knowledge acquisition in genetic and developmental toxicology. As a result of the networked scientific research, synergistic effects are anticipated that favour knowledge in both basic research and translational concepts in distinct areas.

List of research topics and principle investigators (PIs) of the RTG 2578

1a - Comparative analyses of DNA damage response pathways in hepatocytes and neurons differentiated from healthy and NBS-patient derived iPSCs. PI: Adjaye

1b - Hypoxia and Sirtuin 1, two factors linking DNA damage and differentiation in neural stem/ progenitor cells. PIs: Aktas/Berndt

1c -Investigations on DNA repair capacities of human neural progenitor cells (NPC) depending on the degree of differentiation and cell type. PI: Fritsche

1d - Molecular mechanisms regulating the differentiation potential of neural stem and progenitor cells upon gamma irradiation. PIs: Rose/Knobbe-Thomsen

1e - Impact of genotoxins on autophagic processes during neuronal differentiation. PIs: Stork/Adjaye

2a - Effect of DNA damage caused by nephrotoxins and oxidative stress on differentiation and dedifferentiation processes in kidney cells. PI: Schupp

3a - Impact of hemato-oncological therapies on genomic stability and differentiation capacity of human bone marrow-derived mesenchymal stromal cells in the context of therapy-related hematopoietic insufficiency and development of secondary myeloid neoplasms. PI: Schroeder

3b - Sublethal Genomic Damage of Naïve B cells - Consequences for Differentiation and Function with a Focus on Development of Autoimmunity. PI: Pongratz

4 - Influence of nitrosamines and ionizing radiation on the chondrogenic differentiation potential of neonatal and adult stromal cells. PIs: Kögler/Wesselborg

5a - Impact of genotoxins on cardiovascular differentiation of murine and human stem- and progenitor cells: Relevance of mechanisms of DNA repair and DNA damage response (DDR). PI: Fritz

5b - Role of metabolism and mitochondrial function for stem cell differentiation and stress responses upon genotoxic noxae. PIs: Reichert/Fritz

Application for the projects