The primary goal of the program is to assess novel therapeutic candidates in preclinical models of Fanconi anemia (FA). The specific objective of Core C is to systematically evaluate the activity of those FA candidate therapeutic agents in modulating DNA damage response (DDR) and DNA repair using cell-based and biochemical assays. Accordingly, Core C will provide a variety of DDR and DNA repair assay services to the investigators in Projects 1-3.
The specific aims of Core C are: 1) Systematically evaluate the activity of FA therapy small molecule candidates in DDR assays and DNA repair assays, 2) Collect FA cell lines for all in vitro assays, 3) Integrate the data collected by Core C with the data collected by projects 1-3, and 4) Generate publication-grade data for the project and core leaders.
Core C will provide an extensive list of DNA damage and repair assays, including in vitro biochemical assays and cellular assays, for the investigators in the three Projects. Core C will play an essential role in the overall program, facilitating the completion of the aims of each Project. Importantly, Core C will aid in the development of novel therapies for the treatment of bone marrow failure in Fanconi anemia by evaluating a beneficial effects of candidate agents on DNA repair.
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|Kroeger Jr, Paul T; Drummond, Bridgette E; Miceli, Rachel et al. (2017) The zebrafish kidney mutant zeppelin reveals that brca2/fancd1 is essential for pronephros development. Dev Biol 428:148-163|
|Rondinelli, Beatrice; Gogola, Ewa; Yücel, Hatice et al. (2017) EZH2 promotes degradation of stalled replication forks by recruiting MUS81 through histone H3 trimethylation. Nat Cell Biol 19:1371-1378|
|Karras, Georgios I; Yi, Song; Sahni, Nidhi et al. (2017) HSP90 Shapes the Consequences of Human Genetic Variation. Cell 168:856-866.e12|
|Mouw, Kent W; Goldberg, Michael S; Konstantinopoulos, Panagiotis A et al. (2017) DNA Damage and Repair Biomarkers of Immunotherapy Response. Cancer Discov 7:675-693|
|Garbati, Michael R; Hays, Laura E; Rathbun, R Keaney et al. (2016) Cytokine overproduction and crosslinker hypersensitivity are unlinked in Fanconi anemia macrophages. J Leukoc Biol 99:455-65|
|Zhang, Qing-Shuo; Tang, Weiliang; Deater, Matthew et al. (2016) Metformin improves defective hematopoiesis and delays tumor formation in Fanconi anemia mice. Blood 128:2774-2784|
|Zhang, Haojian; Kozono, David E; O'Connor, Kevin W et al. (2016) TGF-? Inhibition Rescues Hematopoietic Stem Cell Defects and Bone Marrow Failure in Fanconi Anemia. Cell Stem Cell 18:668-81|
|Zhang, Qing-Shuo; Benedetti, Eric; Deater, Matthew et al. (2015) Oxymetholone therapy of fanconi anemia suppresses osteopontin transcription and induces hematopoietic stem cell cycling. Stem Cell Reports 4:90-102|
|Lombardi, Anne J; Hoskins, Elizabeth E; Foglesong, Grant D et al. (2015) Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor Sensitivity in Fanconi Anemia Head and Neck Cancers. Clin Cancer Res 21:1962-72|
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