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The research program in the Laboratory of Genome Integrity is focused on the exploration of the causes and effects of genomic instability, mechanisms of DNA repair and the study of DNA repair breakdown as an initiating or protective event in aging and cancers. The program will emphasize a mechanistic understanding of the pathways that maintain genomic integrity, the intersection of these pathways with normal cellular physiology and cancer and the application of these insights to the development of new therapeutic strategies. The laboratory has made major contributions towards a detailed understanding of DNA repair pathway selection as a primary influence on genomic stability and drug resistance/sensitivity in breast and ovarian cancers and the influential role of DNA repair proteins in the promotion of specific hematological malignancies.

The Laboratory is also expanding its efforts in the areas of cellular identity and development by examining the differentiation of hematopoietic stem cells into early T-cell lineage progenitors. This new program will place particular importance towards a comprehensive understanding of the cellular signals that influence hematopoietic progenitor migration, the transcription factors that positively and negatively impact T-cell lineage selection and the contribution of deregulated normal developmental processes in T-cell aging and cancer. The Laboratory of Genome Integrity also manages a state-of-the-art flow cytometry core that houses four cell sorters, four cell analyzers and serves the scientific needs of over 200 scientists and 80 different principal investigators every year. This facility will continue to provide both routine as well as highly specialized sorting services to members of the CCR-NCI community.