RESEARCH


    The primary research interest in the Ruan Lab is to elucidate the structural dynamics and functional interactions of regulatory elements involved in transcription in mammalian genomes. Our primary strategy is to develop innovative genomic technologies along with novel computational analysis tools, and to use integrated approaches to interrogate the genetics and genomics of i) mouse ES cells and differentiated cellular lineages, ii) human hematopoietic stem cells and differentiated immune cells, and iii) complex disorders such as cancer, autoimmune and metabolic diseases. During the course, we have developed a serial of technologies for efficiently characterizing the transcriptomes, epigenomes, and 3D genomes. We first pioneered the paired-end-tag (PET) sequencing strategy for high-throughput, unbiased and quantitative full-length transcriptomic analyses. The pair-end-tagging strategy now has been broadly adapted in most tag-based sequencing practices. We then developed ChIP-PET for genome-wide chromatin immunoprecipitation and protein-binding analysis, which led to the development of the widely known ChIP-Seq. We also developed DNA-PET using paired-end tags of long fragments for identifying genome structural variation. Our most notable achievement is the development of ChIA-PET to map long-range chromatin interactions, which is recognized as a preferred technique for mapping 3D genome folding architectures. Our pioneering efforts in experimental technology development have also necessitated the co-creation of computational tools to process and analyze the unique types of genomic data that our mapping technologies made available. Our pushes in this direction along with others have helped the establishment of the emerging field, 3D genome biology. Our recent development of the droplet-based and barcode-linked strategy (ChIA-Drop) for mapping multiplex chromatin interactions with single molecule/cell precision is propelling the field of 3D genome mapping into a new phase. In addition to being actively involved in the 4D Nucleome to further develop technologies and ENCODE consortia to produce high quality 3D genome maps in a wide range of human and mouse cells, we are ideally positioned in applying the technologies and concepts of 3D genome biology to relevant biomedical questions pertinent to human health and diseases in collaboration with physician scientists.

    Ruan Lab致力于研究哺乳动物染色质结构在生长发育中的动态结构,以及染色质结构对于转录调控的影响。为了达到这个目标,我们开发了多种具有创新性的基因组测序技术和分析工具。我们通过整合这些工具来用于研究不同细胞模型(如小鼠干细胞和人类造血干细胞)以及复杂疾病(如癌症、自身免疫和代谢性疾病)中的遗传学和基因组学问题。 多年来,我们开发了一系列基于Paired-End-Tag(PET)策略的测序技术,用于高效地研究转录组、表观基因组和三维基因组。其中ChIP-PET被用于研究全基因组范围内特定蛋白的结合位点,这项工作引领了广为人知的ChIP-seq技术的开发。此外,我们还开发了DNA-PET,用于识别基因组的结构变异。我们最值得注意的科学贡献是开发了用于探究长距离染色质相互作用的测序技术ChIA-PET,这项技术被认为是研究基因组三维结构的金标准,同时也标志着三维基因组生物学这个新兴领域的诞生。ChIA-PET所独有的基因组数据还促进了下相关处理和分析数据的新型计算工具的产生。我们最近还开发了基于微流控液滴和条形码标记策略的ChIA-Drop技术,揭示了具有单分子、单细胞精度的多重染色质相互作用,正在推动三维基因组检测技术进入一个崭新的阶段。 除了积极参与国际科学组织4D Nucleome和ENCODE以进一步开发新型的测序技术和产生各种人类和小鼠细胞中高质量的三维基因组谱图之外,我们还与其他科学家以及医生合作,将三维基因组生物学中的技术和概念应用于与人类健康和疾病相关的研究中。