The Fanconi anemia repository will support all projects within this PPG by processing and viably cryopreserving marrow and peripheral blood specimens from patients with Fanconi anemia. In addition to processing local samples, Core D will coordinate the shipment and receipt of FA marrow samples from outside collaborating institutions. DNA will be isolated from a portion of the cells for Fanconi anemia subtyping, and the remaining specimens will be viably cryopreserved for the experiments utilizing primary human samples in Project 1, 2, and 3. Marrow stromal cells will also be cultured to support investigations in Project 2. All samples will be labeled with a barcode and entered into our sample database together with clinical annotation for tracking and retrieval. A multiplexed targeted gene capture panel followed by next generation sequencing will be utilized to genotype Fanconi anemia patients who have not undergone clinical subtyping. Confirmatory functional validation assays will be coordinated with Core C as needed for variants of unknown clinical signficiance. De-identified clinical data will be entered into the sample database per IRB-approved protocol. Freshly drawn FA blood samples will be rapidly processed, flash frozen, shipped to collaborators for aldehyde adduct assays. Protein lysates will also be produced from freshly drawn FA samples, frozen, and shipped to collaborators for mass spectrometry analysis of DNA damage response pathways.
Core D Narrative The goal of this program project is to identify safer, more effective drugs that improve blood counts without increasing the risk of clonal evolution in Fanconi anemia. This core will process, characterize, and store biological samples and associated clinical data from patients with Fanconi anemia. The core will also generate lysates for the biochemical studies in the project. These samples are critical to the success of Projects 1, 2, and 3. The TransLab will be ideally poised to perform correlative biological studies for the clinical trial developed in Project 3.
|Whiteaker, Jeffrey R; Zhao, Lei; Ivey, Richard G et al. (2018) Targeted mass spectrometry enables robust quantification of FANCD2 mono-ubiquitination in response to DNA damage. DNA Repair (Amst) 65:47-53|
|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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