The funktionality of DNA damage response pathmays in mammalian somatic stem cells and their role in oncogenic transformation, survival and differentiation

• Applicant: Dr. Leonid Schneider
• Subject Area: Hematology, Oncology
• Term: from 2009 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 131830284

Somatic stem cells ensure tissue homeostasis through their two main capabilities: self renewal and differentiation. DNA damage in stem cells has been implicated in tumourigenesis and ageing. The functionality of molecular DNA damage response (DDR) pathways is thought to be decisive for the elimination of potentially cancerous cells through apoptotic cell death or senescence, with decreasing tissue homeostasis and ageing as side effects. Presently, DDR has been hardly addressed in tissue-specific stem cells, largely due to their poor accessibility. One recently established in vitro stem cell model are the neuronal stem cells (NSC). NSC cultures are homogenous and offer advantages of fast and abundant in vitro propagation. This project would elucidate for the first time the biological properties of stem cells by addressing the functionality of DDR pathways and their role in tumour suppression and tissue homeostasis, since emerging evidence suggests an involvement of the DDR factors also in differentiation processes. We intend to elucidate the roles of DDR kinase ATM and other DDR factors in stem cell survival and differentiation. Also, we would like to contribute to the research of cancer origins by asking whether expression of glyoblastoma-related oncogenes in NSC vs. their terminally differentiated descendants leads to senescence, apoptosis, transformation or de-differentiation.

• DFG Programme: Research Fellowships
• International Connection: Italy
• Host: Dr. Fabrizio d' Adda di Fagagna