Regulation of Transcriptional Responses to DNA Damage
- McDonnell Pediatric Cancer Center
2/1/2009 - 1/31/2011
Sensing and repairing DNA breaks are essential processes in preserving the integrity of the genome. When presented with potentially toxic DNA damage, cells immediately activate a sophisticated signaling network to ensure proper repair and prevent abnormalities that can lead to malignancies. Deficiencies in the DNA damage response affect cancer predisposition, treatment responses, and treatment toxicities. Previous work in the Sleckman lab has shown that DNA breaks initiate gene expression changes that impact the development of the immune system. The goals of this project are 1) to define the DNA damage-induced signals that are important in regulating gene expression and 2) to identify the factors that integrate DNA damage responses with normal immune signals. Characterizing these associations will provide insight into immune development and how breakdowns in the system can predispose to leukemias and lymphomas. This research will also reveal how DNA damaging agents, such as chemotherapy and radiation, can corrupt immune development and function. Ultimately, this work will establish important links between how immune cells respond to DNA damage and how this response impacts cancer development, treatment and therapy side effects. The results will hopefully identify new avenues for treatment of pediatric malignancies that are more effective and less toxic.