Despite the rapidly increasing capacity to sequence human genomes, our incomplete ability to read and interpret the information content in genomes and epigenomes remain a central challenge. A comprehensive set of regulatory events across a genome - the regulome - is needed to make full use of genomic information, but is currently out of reach for practically all clinical applications and many biological systems The proposed Center will develop technologies that greatly increase the sensitivity, speed, and comprehensiveness of understanding genome regulation. We will develop new technologies to interrogate the transactions between the genome and regulatory factors, such as proteins and noncoding RNAs, and integrate variations in DNA sequences and chromatin states over time and across individuals. Novel molecular engineering and biosensor strategies are deployed to encapsulate the desired complex DNA transformations into the probe system, such that the probe system can be directly used on very small human clinical samples and capture genome-wide information in one or two steps. These technologies will be applied to clinical samples and workflows in real time to exercise their robustness and reveal for the first time epigenomic dynamics of human diseases during progression and treatment. These technologies will be broadly applicable to many biomedical investigations, and the Center will disseminate the technologies via training and diverse means.
How genes are turned on and off govern the outcome and treatments of many human diseases. By making it possible to track all the genetic switches rapidly and comprehensively from small human biopsies, the Center aims to greatly improve the precision and effectiveness of disease diagnosis and treatment, such as for cancer, autoimmunity, and neurodegenerative diseases.
|Denny, Sarah K; Yang, Dian; Chuang, Chen-Hua et al. (2016) Nfib Promotes Metastasis through a Widespread Increase in Chromatin Accessibility. Cell 166:328-42|
|Giorgetti, Luca; Lajoie, Bryan R; Carter, Ava C et al. (2016) Structural organization of the inactive X chromosome in the mouse. Nature 535:575-9|
|Corces, M Ryan; Buenrostro, Jason D; Wu, Beijing et al. (2016) Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution. Nat Genet 48:1193-203|
|Araya, Carlos L; Cenik, Can; Reuter, Jason A et al. (2016) Identification of significantly mutated regions across cancer types highlights a rich landscape of functional molecular alterations. Nat Genet 48:117-25|
|Yu, Kun-Hsing; Li, Jingjing; Snyder, Michael et al. (2016) The genetic predisposition to bronchopulmonary dysplasia. Curr Opin Pediatr 28:318-23|
|Huang, Wei-Hsiang; Guenthner, Casey J; Xu, Jin et al. (2016) Molecular and Neural Functions of Rai1, the Causal Gene for Smith-Magenis Syndrome. Neuron 92:392-406|
|Flynn, Ryan A; Do, Brian T; Rubin, Adam J et al. (2016) 7SK-BAF axis controls pervasive transcription at enhancers. Nat Struct Mol Biol 23:231-8|
|Flynn, Ryan A; Zhang, Qiangfeng Cliff; Spitale, Robert C et al. (2016) Transcriptome-wide interrogation of RNA secondary structure in living cells with icSHAPE. Nat Protoc 11:273-90|
|Atianand, Maninjay K; Hu, Wenqian; Satpathy, Ansuman T et al. (2016) A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation. Cell 165:1672-85|
|Lu, Zhipeng; Zhang, Qiangfeng Cliff; Lee, Byron et al. (2016) RNA Duplex Map in Living Cells Reveals Higher-Order Transcriptome Structure. Cell 165:1267-79|
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