研究领域
1. 课题组成功研发了超微量，低成本单碱基分辨率的表观基因组和转录组检测技术，该技术不依赖于高通量测序，仅需1 ng 血液中抽提的cfDNA就可以低成本（低至300元）检测DNA甲基化和RNA m6A修饰进行单碱基分辨率的定量分析，无需复杂的数据处理，使用简单方便，用户友好，在临床方向有很好的应用前景。
2. 课题组基于“split-pool”策略成功开发了单细胞尺度的DNA 5hmC测序技术，可以基于DNA 5hmC修饰对神经细胞进行精细分群，为研究脑科学和脑疾病中的单细胞DNA 5hmC特征提供了实用的工具。
3. 研发检测RNA亚细胞定位的新技术。目前研究RNA亚细胞定位的技术APEX-Seq需要过表达质粒或者慢病毒感染，对细胞状态影响较大。课题组开发无需过表达质粒或者慢病毒感染的原位扩增技术，来检测无膜细胞器例如P-body, nuclear speckle, stress granule 和autophagosome中的RNA含量和丰度。
4. 以往的认知中，细胞膜外表面分布着蛋白质，脂类以及糖链修饰，然而最新的研究表明，细胞膜外表面存在被糖基化修饰的RNA。有一些膜蛋白，例如P62细胞自噬受体受到小RNA的调控。课题组研发细胞膜外表面RNA的扩增和检测技术，并且专注于研究细胞膜外表面RNA的结合蛋白和详细功能，探索受到RNA调控的膜蛋白种类和具体机制。
近期论文
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Weizhi He*, Xiaotong Yin*, Chu Xu*, Xiangyue Liu, Yue Huang, Caiguang Yang, Yanhui Xu, and Lulu Hu#. Ascorbic Acid Reprograms Epigenome and Epitranscriptome by Reducing Fe (III) in the Catalytic Cycle of Dioxygenases. ACS Chem Biol. 2023 Dec 15.
Ruiqi Ge, Chang Ye, Yong Peng, Qing Dai, Yutao Zhao, Shun Liu, Pingluan Wang, Lulu Hu#, Chuan He# m6A-SAC-seq for quantitative whole transcriptome m6A profiling. Nat Protoc. 2023 Feb;18(2):626-657. doi: 10.1038/s41596-022-00765-9.
Hu L*#, Liu S*, Peng Y*, Ge R*, Su R*, Senevirathne C, Harada BT, Dai Q, Wei J, Zhang L, Hao Z, Luo L, Wang H, Wang Y, Luo M, Chen M#, Chen J#, He C#. m6A RNA modifications are measured at single-base resolution across the mammalian transcriptome. Nat Biotechnol. 2022 Aug;40(8):1210-1219. doi: 10.1038/s41587-022-01243-z. Epub 2022 Mar 14.
Yong Peng, Hanzhe Meng, Ruiqi Ge, Shun Liu, Mengjie Chen, Chuan He, Lulu Hu#. Detection of m6A RNA modifications at single-nucleotide resolution using m6A-selective allyl chemical labeling and sequencing. STAR Protoc. 2022 Dec 16;3(4):101677. doi: 10.1016/j.xpro.2022.101677.
Lulu Hu#. Quantitative and single nucleotide RNA m6 A detection technology boosts clinical research based on tissue and cell free RNA modification. Clin Transl Med. 2022 Oct;12(10): e1082. doi: 10.1002/ctm2.1082.
Hu L*, Liu Y*, Han S*, Yang L*, Cui X, Gao Y, Dai Q, Lu X, Kou X, Zhao Y, Sheng W, Gao S, He X, He C. Jump-seq: Genome-Wide Capture and Amplification of 5-Hydroxymethylcytosine Sites. J Am Chem Soc. 2019 Jun 5;141(22):8694-8697. doi: 10.1021/jacs.9b02512. Epub 2019 May 23.
Zhang LS, Liu C, Ma H, Dai Q, Sun HL, Luo G, Zhang Z, Zhang L, Hu L, Dong X, He C. Transcriptome-wide Mapping of Internal N7-Methylguanosine Methylome in Mammalian mRNA. Mol Cell. 2019 Jun 20;74(6):1304-1316.e8. doi: 10.1016/j.molcel.2019.03.036. Epub 2019 Apr 25.
Ji L, Jordan WT, Shi X, Hu L, He C, Schmitz RJ. TET-mediated epimutagenesis of the Arabidopsis thaliana methylome. Nat Commun. 2018 Mar 1;9(1):895. doi: 10.1038/s41467-018-03289-7.
Wang W, Xu L, Hu L, Chong J, He C, Wang D. Epigenetic DNA Modification N6-Methyladenine Causes Site-Specific RNA Polymerase II Transcriptional Pausing. J Am Chem Soc. 2017 Oct 18;139(41):14436-14442. doi: 10.1021/jacs.7b06381. Epub 2017 Oct 3.
Lu J*, Hu L*, Cheng J, Fang D, Wang C, Yu K, Jiang H, Cui Q, Xu Y, Luo C. A computational investigation on the substrate preference of ten-eleven-translocation 2 (TET2). Phys Chem Chem Phys. 2016 Feb 14;18(6):4728-38. doi: 10.1039/c5cp07266b.
Hu L, He C. Detecting hepatocellular carcinoma in blood. Cell Res. 2015 Dec;25(12):1279-80. doi: 10.1038/cr.2015.136. Epub 2015 Nov 24.
Hu L*, Lu J*, Cheng J*, Rao Q, Li Z, Hou H, Lou Z, Zhang L, Li W, Gong W, Liu M, Sun C, Yin X, Li J, Tan X, Wang P, Wang Y, Fang D, Cui Q, Yang P, He C, Jiang H, Luo C, Xu Y. Structural insight into substrate preference for TET-mediated oxidation. Nature2015 Nov 5;527(7576):118-22.
Hu L*, Li Z*, Cheng J*, Rao Q, Gong W, Liu M, Shi YG, Zhu J, Wang P, Xu Y. Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation. Cell2013 Dec 19;155(7):1545-55 .
Hu L*, Li Z*, Wang P, Lin Y, Xu Y. Crystal structure of PHD domain of UHRF1 and insights into recognition of unmodified histone H3 arginine residue 2. Cell Res. 2011 Sep;21(9):1374-8.
Rajakumara E*, Wang Z*, Ma H, Hu L, Chen H, Lin Y, Guo R, Wu F, Li H, Lan F, Shi YG, Xu Y, Patel DJ, Shi Y. PHD finger recognition of unmodified histone H3R2 links UHRF1 to regulation of euchromatic gene expression. Mol. Cell2011 Jul 22;43(2):275-84 .
Yang Y*, Hu L*, Wang P*, Hou H, Lin Y, Liu Y, Li Z, Gong R, Feng X, Zhou L, Zhang W, Dong Y, Yang H, Lin H, Wang Y, Chen CD, Xu Y.Structural insights into a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans. Cell Res. 2010 Aug;20(8):886-98 .
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