研究团队组建于2013年，团队研究方向为儿童出生缺陷、神经发育障碍的遗传基础。我们利用多个基因组技术结合传统遗传学技术、常规分子生物学技术和多潜能干细胞、动物的基因编辑模式，研究基因突变致病机理。

团队现有高级职称2名，中级职称和技术员各1名，研究生4名。

在研主持项目：

1.        北京市财政项目“儿童重大遗传病发病机制及临床干预策略研究项目“2024年1月1日-2025年12月30日，合作PI，在研，110万

2.        MARK2突变通过抑制神经元发育早期的WNT/β-catenin信号通路导致孤独症发生，国家自然基金面上项目，82371868，50万，2024/01/01-2027/12/31，在研，主持

3.        北京财政改革和发展项目，剩余单体型和16p11.2微缺失表型异质性的关系，2023/07/01-2026/04/30，36.8万，在研，主持,

SCI publications of Xiaoli Chen as first (#) or correspondencing (*) authors (近十年)

1.        Maolei Gong , Jiayi Li ,Zailong Qin , Matheus Vernet Machado Bressan Wilke, Yijun Liu , Qian Li ,Haoran Liu , Chen Liang, Joel A Morales-Rosado, Ana S.A. Cohen, Susan S.Hughes, Bonnie R. Sullivan, Valerie Waddell , Marie-José H. van den Boogaard,Richard H. van Jaarsveld, Ellen van Binsbergen, Koen L van Gassen, TianyunWang, Susan M. Hiatt, Michelle D. Amaral, Whitley V. Kelley, Jianbo Zhao,Weixing Feng, Changhong Ren, Yazhen Yu, Nicole J Boczek, Matthew J. Ferber,Carrie Lahner, Sherr Elliott, Yiyan Ruan, Mignot Cyril, Boris Keren, Hua Xie,Xiaoyan Wang, Bernt Popp, Christiane Zweier , Juliette Piard , ChristineCoubes, Frederic Tran Mau-Them, Hana Safraou, A. Micheil Innes, Julie Gauthier,Jacques Michaud, Daniel C. Koboldt, Odent Sylvie, Marjolaine Willems, Wen-HannTan, Benjamin Cogne , Claudine Rieubland , Dominique Braun, Scott DouglasMcLean , Konrad Platzer, Pia Zacher, Henry Oppermann, Lucie Evenepoel, PierreBlanc, Laïla El Khattabi, Neshatul Haque, Nikita R. Dsouza, Michael T. Zimmermann,Raul Urrutia, Eric W Klee, Yiping Shen, Hongzhen Du, Chang-Mei Liu* and Xiaoli Chen*. MARK2 variants causeautism spectrum disorder viathe downregulation of WNT/β-catenin signalingpathway, Am J Hum Genet ., 2024, 16th,Oct.online( JCR Q1, IF=8.1)

2.        Shaofang Shangguan#, XueyuanZhang#, Yangyang Ge, Ye Han, Ling Xiao, Yu Zhang, Hua Xie, Xiaoli Chen*, Xiaoyan Wang*. Confirming the enzymatic activity andneurodevelopmental trajectory of PYCR1 mutation in one child withautosomal-recessive cutis laxa type 2.  MolecularGenetics and Genomics. doi: 10.1007/s00438-024-02173-y. (JCR Q3, IF=2.3)

3.        Ye Han#, Yangyang Ge#, HaoranLiu, Liying Liu, Lina Xie, Xiaoli Chen*,Qian Chen*. A novel compound heterozygous mutation of UFC1 in a patient withneurodevelopmental disorder. Genes & Genomics, 2024Sep;46(9):1037-1043. doi: 10.1007/s13258-024-01543-5. (JCR Q3, IF=1.6)

1.        Qingming Wang#, Ye Han#, Xinlong Zhou, ShuangXiCheng, Xin Wang, Xiaoli Chen*, Haiming Yuan*. RNASEH2C c.194G>A is aChinese-specific founder mutation in three unrelated patients withAicardi-Goutières syndrome 3. Clin Genet. 2023 Aug;104(2):259-265.doi: 10.1111/cge.14343. Epub 2023 Apr 24.IF=4.2, Q2

2.        Hui Yin#, Hua Xie#,Jizhen Zou, Xue Ye, Ying Liu, Cai He, Shaofang Shangguan, Haoran Liu, XiaoliChen*, Xiaobo Chen*. A mosaic karyotype of 45,X/46,X,psu idic(Y)(q12) in aten-year-old boy: integrating high-throughput sequencing with cytogenetictechnique for precise diagnosis and genetic counselling. BMC Pediatr. 2023 Mar4;23(1):104. doi: 10.1186/s12887-023-03872-y. IF= 2.567, Q3

3.        Fang Liu, Chen Liang, Zhengchang Li, Sen Zhao,Haiming Yuan, Ruen Yao, Zailong Qin, Shaofang Shangguan, Shujie Zhang, Li-PingZou, Qian Chen, Zhijie Gao, Suiwen Wen, Jing Peng, Fei Yin, Fei Chen, XiaoxiaQiu, Jingsi Luo, Yingjun Xie, Dian Lu, Yu Zhang, Hua Xie, Guozhuang Li, TerryJianguo Zhang, Pengfei Luan, Hongying Wang, Xiaodai Cui, Hailiang Huang, RuizeLiu, Xiaofang Sun, Chao Chen, Nan Wu, Jian Wang, Chunyu Liu, Yiping Shen, JamesF. Gusella, Xiaoli Chen*. Haplotype-specific MAPK3 expression in 16p11.2deletion contributes to variable neurodevelopment. Brain, 2023 Mar 3;awad071. doi: 10.1093/brain/awad071.IF=15, Q1.

4.        Hua Xie#, Hui Yin#, Xue Ye, Ying Liu, Na Liu, YuZhang, Xiaoli Chen*, Xiaobo Chen*, Detection of small CYP11B1 deletionsand one founder chimeric CYP11B2/CYP11B1 gene in 11β-hydroxylase deficiency. Front.Endocrinol., 2022 May 24;13:882863. doi: 10.3389/fendo.2022.882863.IF=6.05 Q1,

5.        Yu Tian#, Hua Xie#, Shenghai Yang, ShaofangShangguan, Jianhong Wang, Chunhua Jin, Yu Zhang, Xiaodai Cui, Yanyu Lyu, XiaoliChen*, Lin Wang*. Possible Catch-Up Developmental Trajectories for Childrenwith Mild Developmental Delay Caused by NAA15 Pathogenic Variants. Genes(Basel).2022;13(3):536. doi: 10.3390/genes13030536.IF=4.14, Q2

6.        Liying Liu#, Fang Liu#, Qiuhong Wang, Hua Xie,Zhengchang Li, Qian Lu, Yangyang Wang, Mengna Zhang, Yu Zhang, Jonathan Picker,Xiaodai Cui, Liping Zou, Xiaoli Chen*. Confirming the contribution andgenetic spectrum of de novo mutation in infantile spasms: Evidence from aChinese cohort. Mol Genet Genomic Med. 2021 Jun;9(6):e1689. doi:10.1002/mgg3.1689. Epub 2021 May 5. IF=2.87, Q3

7.        Haiming Yuan#, Shaofang Shangguan#, ZhengchangLi#, Jingsi Luo#, Jiasun Su#, Ruen Yao, Shun Zhang, Chen Liang, Qian Chen, Zhijie Gao, Yanli Zhu, Shujie Zhang, WeiLi, Weiliang Lu, Yu Zhang, Hua Xie, Fang Liu,Qingming Wang, Yangyang Lin, Liying Liu, XiumingWang, Liyang Liang, Jianmin Zhong, Haibo Li, Haiyan Qiu, Huifeng Zhang, MeiYan, Maimaiti Mireguli, Yanhui Liu, Dan Zhang, Hongying Wang, Haitao Lv, BoboXie, Chunrong Gui, Xiaodai Cui, Liping Zou, Jian Wang, James F. Gusella, YipingShen*, Xiaoli Chen*. CNV profiles ofChinese pediatric patients with developmental disorders. Genet Med. 2021Apr;23(4):669-678. doi: 10.1038/s41436-020-01048-y. Epub 2021 Jan 5. IF=8.9, Q1

8.        Hua Xie#, Fang Liu#,Yu Zhang, Qian Chen, Shaofang Shangguan, Zhijie Gao, Nan Wu, Jian Wang, XiaodaiCui, Lin Wang*, Xiaoli Chen*. Neurodevelopmental trajectory and modifiers of 16p11.2microdeletion: A follow-up study of four Chinese children carriers. Mol Genet Genomic Med. 2020 Sep 1;e1485. doi: 10.1002/mgg3.1485. IF=2.87, Q3

9.        Juanjuan Li, Junhui Li(co-first author), Jianguo Li, Hailan Yao, Fang Liu, James F Gusella, XiaodongShi*, Xiaoli Chen*. A rare case of acquired immunodeficiency associated withmyelodysplastic syndrome. Mol Genet Genomic Med. 2019 Nov;7(11):e923.doi: 10.1002/mgg3.923. Epub 2019 Sep 10. IF=2.87, Q3

10.     Li H, Zhu Y, Morozov YM, Chen X,Page SC, Rannals MD, Maher BJ, Rakic P. Disruption of TCF4 regulatory networksleads to abnormal cortical development and mental disabilities. Mol Psychiatry. 2019 Jan 31. doi: 10.1038/s41380-019-0353-0. IF=11.97, Q1

11.     Liu J, Wu N,Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, YangN, Takeda K, Chen W, Li W, Du R, Liu S, Zhou Y, Zhang L, Liu Z, Zuo Y, Zhao S,Blank R, Pehlivan D, Dong S, Zhang J, Shen J, Si N, Wang Y, Liu G, Li S, ZhaoY, Zhao H, Chen Y, Zhao Y, Song X, Hu J, Lin M, Tian Y, Yuan B, Yu K, Niu Y, YuB, Li X, Chen J, Yan Z, Zhu Q, Meng X, Chen X, Su J, Zhao X, Wang X,Ming Y, Li X, Raggio CL, Zhang B, Weng X, Zhang S, Zhang X, Watanabe K,Matsumoto M; Japan Early Onset Scoliosis Research Group, Jin L, Shen Y,Sobreira N, Posey JE, Giampietro PF, Valle D30; Baylor-Hopkins Center forMendelian Genomics, Liu P, Wu Z, Ikegawa S, Lupski JR, Zhang F, Qiu G.TBX6-associated congenital scoliosis (TACS) as a clinically distinguishablesubtype of congenital scoliosis: further evidence supporting the compoundinheritance and TBX6 gene dosage model, Genet Med. 2019 Jan 14. doi:10.1038/s41436-018-0377-x. . IF=8.9, Q1

12.     Jiang Q, ChenX, Zhang F, Chakravarti A, Li L. Response to Brosens et al. GenetMed. 2018 Nov;20(11):1479-1480. doi: 10.1038/gim.2018.7. IF=8.9, Q1

13.    Zhijie Gao, Hua Xie, Qian Jiang, Nan Wu, Xiaoli Chen*, Qian Chen*, Identificationof two novel null variants of CLN8 by targeted next-generation sequencing:First report of a Chinese patient with neuronal ceroid lipofuscinosis dueto CLN8 variants. BMC Medical Genetics. 2018, 201819:21 DOI: 10.1186/s12881-018-0535-7.IF=1.74.

14.    Qian Jiang, Fang Liu, Chunyue Miao, Qi Li, ZhenZhang, Ping Xiao, Lin Su, Kaihui Yu, Xiaoli Chen, Feng Zhang, AravindaChakravarti, Long Li. RET somatic mutations are underrecognized in Hirschsprungdisease, Genet Med. 2017. doi:10.1038/gim.2017.178. . IF=8.9, Q1

15.     Zhu Q, Wu N, Liu G, Zhou Y, Liu S, Chen J, Liu J, Zuo Y, Liu Z, Chen W, Chen Y, Chen J, Lin M, Zhao Y, Yang Y, Wang S, Yang X, Ma Y, Wang J, Chen X, Zhang J, Shen J, Wu Z, Qiu G. Comparativeanalysis of serum proteome in congenital scoliosis patients with TBX6haploinsufficiency- a first report pointing to lipid metabolism. J Cell Mol Med. 2017. doi: 10.1111/jcmm.13341.

16.     Xiaoyan Li, HuaXie, Qian Chen, Xiongying Yu, Zhaoshi Yi, Erzhen Li, Ting Zhang, Jian Wang,Jianmin Zhong*, Xiaoli Chen*. Clinical and Molecular GeneticCharacterization of Familial MECP2 Duplication Syndrome in a Chinese Family. BMCMedical Genetics. 2017 Nov 15;18(1):131. DOI: 10.1186/s12881-017-0486-4. 4, Q3,IF=1.74

17.     Hua Xie, Xiaoyan Li, Jiping Peng, Qian Chen, ZhiJie Gao,Xiaozhen Song,WeiYu Li, Jianqiu Xiao, Caihua Li, Ting Zhang, James F Gusella,Jianmin Zhong*, Xiaoli Chen*. A complex intragenicrearrangement of ERCC8 in Chinese siblings with Cockayne syndrome Sci Rep. 2017 Mar 23;7:44271.doi: 10.1038/srep44271. IF=4.99, Q1 

18.     Xiaoli Chen, Yu An, Yonghui Gao, Liu Guo, Lei Rui, Hua Xie, Mei Sun,Siv Lam Hung, Xiaoming Sheng, Jizhen Zou, Yihua Bao, Hongyan Guan, Bo Niu,Zandong Li, Richard H. Finnell, James F. Gusella, Bai-Lin Wu, Ting Zhang. Raredeleterious PARD3 variants in the aPKC-binding region are implicated in thepathogenesis of human cranial neural tube defects via disrupting apical tightjunction formation. HumMutat., 2017 Apr. 15;38(4):378-389. doi: 10.1002/humu.23153. Epub 2017 Feb 15, IF=5.35, Q1

19.     Hu X, ChenX, Wu B, Soler IM, ChenS, Shen Y. Further defining the critical genesfor the 4q21 microdeletion disorder. AmJ Med Genet A. 2017 Jan;173(1):120-125. doi: 10.1002/ajmg.a.37965. (IF=2.19)

20.     Tai DJ, Ragavendran A, Manavalan P, Stortchevoi A, Seabra CM, Erdin S, Collins RL, Blumenthal I, Chen X, Shen Y, Sahin M, Zhang C, Lee C, Gusella JF, Talkowski ME*. Engineering microdeletions and microduplications bytargeting segmental duplications with CRISPR. Nat Neurosci. 2016Mar;19(3):517-22. doi: 10.1038/nn.4235. (IF=21.12)

21.     An Y, Duan W, Huang G, ChenX, Li L, Nie C, Hou J, Gui Y, Wu Y, ZhangF, Shen Y, Wu B, Wang H. Genome-wide copy numbervariant analysis for congenital ventricular septal defects in Chinese Hanpopulation. BMC Med Genomics. 2016Jan 8;9:2. doi: 10.1186/s12920-015-0163-4.

22.     Li Q, Zhang Z, Yan Y, Xiao P, Gao Z, Cheng W, Su L, Yu K,Xie H, Chen X,Jiang Q, Li L. Annular pancreas inTrichorhinophalangeal syndrome type II with 8q23.3-q24.12 interstitialdeletion. Mol Cytogenet. 2015Dec 15;8:95. doi: 10.1186/s13039-015-0201-0. eCollection 2015.

23.    Wu N, Ming X, Xiao J, Wu Z, Chen X(co-first author), Shinawi M, Shen Y, Yu G, Liu J, Xie H, Gucev ZS, Liu S, Yang N, Al-Kateb H, Chen J, Zhang J, Hauser N, Zhang T, Tasic V, Liu P, Su X, Pan X, Liu C, Wang L, Shen J, Shen J, Chen Y, Zhang T, Zhang J, Choy KW, Wang J, Wang Q, Li S, Zhou W, Guo J, Wang Y, Zhang C, Zhao H, An Y, Zhao Y, Wang J, Liu Z, Zuo Y, Tian Y, Weng X, Sutton VR, Wang H, Ming Y, Kulkarni S, Zhong TP, Giampietro PF, Dunwoodie SL, Cheung SW, Zhang X, Jin L, Lupski JR, Qiu G, Zhang F. TBX6 null variants and a common hypomorphic allele incongenital scoliosis. N Engl J Med. 2015 Jan22;372(4):341-50. doi: 10.1056/NEJMoa1406829. Epub 2015 Jan 7.9. Q1, IF=76

24.     Chen X*, Wang J,Xie H,Zhou W,Wu Y,Wang J,Qin J,Guo J,Gu Q,Zhang X,Ji T,Zhang Y,Xiong Z,Wang L,Wu X,Latham GJ,Jiang Y*.Fragile X syndrome screening in Chinese children with unknown intellectualdevelopmental disorder. BMC Pediatr. 2015 Jul 15;15:77. doi:10.1186/s12887-015-0394-8. Q3, IF=1.74

25.     Xiaoli Chen*, Jun Wang, ElyseMitchell, Jin Guo, Liwen Wang, Yu Zhang, Jennelle C Hodge and Yiping Shen*.Recurrent 8q13.2-13.3 microdeletions associated with Branchio-oto-renalsyndrome are mediated by human endogenous retroviral (HERV) sequence blocks. BMCMedical Genetics, 2014, 19;15(1):90. IF=1.74

博士和博士后

本课题组特色：

1.   课题组经费充足、环境宽松、学术气氛活跃。

2.   可以获得综合、全面的科研训练，同时每位学生每年都将有机会参加各大学术会议，近距离接触最新的科研进展。

3.   课题组会定期组织聚餐、出游，丰富大家的课余生活。

导师需求：

    招收博士层次的学生，培养单位为首都儿科研究所，理论课学习均在协和研究生院完成，毕业授予北京协和医学院博士学位。

1.   我们期待学生保有一颗热爱科研的初心，踏实刻苦，有较好的逻辑思维能力，沟通表达、组织协调的能力，积极主动提出问题，并通过自身努力解决问题。

2.   我们对学生本科学校和具体专业不做特定要求，实验室同时具备湿性实验和干性实验的实验条件，可以根据学生的个人意愿，自由选择进行分子生物学实验的课题或者侧重生物信息学分析的课题。

3.   我们期待学生对大规模数据分析有一定的敏感性，准备进行生物信息学分析课题的学生能掌握至少一种计算机语言，有较强的统计基础。

博士生研究方向：

    儿童神经发育障碍疾病的基因组结构特点和致病机理，比如发育迟缓，孤独症，智力认知迟滞。

1.   儿童神经发育障碍疾病的基因组结构特点。结合儿童神经心理发育量表、全外显子组测序和芯片、常规家庭问卷，探索不同年龄的儿童神经发育迟缓（<5岁）/障碍（>5岁）的基因组结构和遗传特点，基因型和临床表型之间的关系。既包括探索该疾病新致病基因，同时也利用既往GWAS数据库探索该疾病的多基因效应模式（PRS）。需要使用多种基因组数据库（ENCODE、PsychENCODE、Brain eQTL、denovo-db、ASC exome sequencing data）进行数据挖掘，具备R和Python编程能力。欢迎具有以下研究经验者申报：基因组数据的生信分析经验、神经发育障碍相关疾病的遗传研究背景。

2.   基因突变导致儿童神经发育障碍疾病的致病机理。利用基因突变患者来源的外周血转成干细胞、再定向分化为神经干细胞，从神经电生理，能量代谢，神经炎症和生物学特效揭示疾病发生基础，之后尝试靶向药物筛选和基因编辑治疗。希望具有基因组数据分析、神经干细胞培养分化、电生理、能量代谢和常规分子生物学的背景基础的人员报考。

你将收获：

1.   更加全面丰富的遗传学、分子生物学及生物信息学知识。

2.   提高收集文献、处理文献的能力，及独立科研的能力，对本领域国内外知名学者的工作可以进行密切跟踪！

3.   分析和独立思考的能力，学习成绩只是一种表象的结果，而学习能力才是伴随一生的能力。

4.   提升自信心，每周的组会学习，定期的文献、课题进展汇报，课题组内成员共同探讨学习，沟通表达能力也会得到显著提升。

1.   课题组年度会议筹备

2.   丰富的参会学习机会

3.   积极申请参与学术会议投稿、发言

4.   我们是相亲相爱的一家人