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李明  研究员
转化基因组学科组
职  务: 转化基因组实验室负责人
学  历: 理学博士
电  话: +86 871 65189508
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电子邮件: limingkiz@mail.kiz.ac.cn
通讯地址: 云南省昆明市盘龙区茨坝街道龙欣路17号 中国科学院昆明动物研究所    650201
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  简  历

博士,研究员,博士生导师。2008年毕业于武汉大学生命科学学院获学士学位,2013年于中国科学院昆明动物研究所获遗传学博士学位,同年赴约翰霍普金斯大学医学院利伯脑发育研究所从事博士后研究工作,2016年回昆明动物研究所工作,建立转化基因组学科组。主要从事重性精神疾病及相关人类复杂性状(脑结构、创造力、认知功能等)的遗传学和基因组学研究,致力于寻找影响上述疾病及表型的基因组变异,并探索其在有关细胞功能、神经环路及行为表型等生理学过程中发挥作用的可能机制。在国际上首次描述了精神疾病相关基因组区域10q24.32参与疾病发生的可能机制,鉴定到一个由可变剪接所致并显著增加精神疾病风险的人类特异蛋白(Nature Medicine 2016;22(6):649-656);创新性的详尽证实了精神疾病中三维基因组的分子调控模式(Biological Psychiatry 2021;89(3):246-255);此外,率先开展了中国人群中双相情感障碍的系统遗传学分析,为理解我国人群中该疾病的遗传基础提供了重要视角(JAMA Psychiatry 2021)。近年来以通讯或第一作者(含共同)Nature MedicineJAMA PsychiatryMolecular PsychiatryAmerican Journal of PsychiatryBiological PsychiatryScience BulletinSchizophrenia BulletinBritish Journal of PsychiatryNeuropsychopharmacology等期刊发表论文。现任中国神经科学学会精神病学基础与临床分会(CSNP)委员、Functional & Integrative Genomics期刊Section Editor(人类基因组方向)、Scientific Reports期刊学术编辑、Complex Psychiatry期刊编委、Journal of Psychiatry and Brain Science期刊编委。

  研究方向

以双相情感障碍和抑郁症为代表的多种重性精神疾病严重影响了人类健康,患者往往表现出情绪和认知方面的障碍,严重影响正常生活,甚至导致一系列机体疾病发病率和自杀率的升高。累积研究表明遗传因素(如DNA变异、基因等)在精神疾病发生发展中起到了关键作用,但仍有很多核心科学问题有待回答。首先,中国人群中精神疾病遗传基础的研究尚处于初步阶段,仍有许多遗传风险因素有待鉴定;同时,单纯遗传学分析无法直接鉴定真正参与疾病发生的功能性DNA变异或基因,也不足以揭示有关的病理生理机制;此外,精神疾病具有表型上的高度复杂性,特定疾病患者往往存在高度异质性,而不同疾病患者大多又共享部分症状,为针对性诊治带来了难题,因此,系统解析疾病有关表型的遗传决定因素对于深入认识和有效控制疾病也有着重大意义。针对上述科学问题,我们聚焦双相情感障碍和抑郁症等重性精神疾病,致力于系统寻找功能性遗传风险因素,并探索其如何调控易感基因表达及功能,进而改变细胞发育、大脑功能及行为表型。目前的主要研究方向概括如下:

1. 利用遗传学、生物信息学等多组学分析,比较中国人群中精神疾病患者与健康对照个体间遗传背景的差异,鉴定与疾病风险显著相关的DNA变异。

2. 筛选上述精神疾病风险DNA变异中可能产生生物学功能影响的变异,分析它们对基因转录与功能的影响,从而揭示相关分子调控机制,推测其在疾病发生中的作用。

3. 在细胞及模式动物中探讨风险DNA变异和易感基因影响疾病发生的生物学机制,结合其与相关药物的交互作用情况,寻找未来精神疾病新药物与疗法的潜在靶标。

  承担科研项目
  专家类别
研究员
  社会任职
  获奖及荣誉
  代表论著

#共同第一作者;*通讯作者)

1.        Zhang CY, Xiao X, Zhang Z, Hu Z,* Li M.* An alternative splicing hypothesis for neuropathology of schizophrenia: evidence from studies on historical candidate genes and multi-omics data. Molecular Psychiatry 2021; in proof.

2.        Li HJ,# Zhang C,# Hui L,# Zhou DS, Li Y, Zhang CY, Wang C, Wang L, Li W, Yang Y, Qu N, Tang J, He Y, Zhou J, Yang Z, Li X, Cai J, Yang L, Chen J, Fan W, Tang W, Tang W, Jia QF, Liu W, Zhuo C, Song X, Liu F, Bai Y, Zhong BL, Zhang SF, Chen J, Xia B, Lv L, Liu Z, Hu S, Li XY, Liu JW, Cai X, Yao YG, Zhang Y, Yan H, Chang S, Zhao JP, Yue WH, Luo XJ, Chen X, Xiao X, Fang Y,* Li M,* for the GeseDNA Research Team. Novel risk loci associated with genetic risk for bipolar disorder among Han Chinese individuals: A genome-wide association study and meta-analysis. JAMA Psychiatry 2021; DOI:10.1001/jamapsychiatry.2020.3738.

3.        Chang H,# Cai X,# Li HJ,# Liu WP, Zhao LJ, Zhang CY, Wang JY, Liu JW, Ma XL, Wang L, Yao YG, Luo XJ, Li M,* Xiao X.* Functional genomics identify a regulatory risk variation rs4420550 in the 16p11.2 schizophrenia-associated locus. Biological Psychiatry 2021; 89(3):246-255. (Cover story)

4.        Zhang C,# Xiao X,# Li T,* Li M.* Translational genomics and beyond in bipolar disorder. Molecular Psychiatry 2021; 26:186-202.

5.        Cao X,# Liu WP,# Cheng L, Li HJ, Wu H, Liu Y, Chen C, Xiao X, Li M,* Wang GD,* Zhang YP.* Whole genome analyses reveal significant convergence in obsessive-compulsive disorder between humans and dogs. Science Bulletin 2021; 66:187-196.

6.        Cai X,# Yang ZH,# Li HJ, Xiao X, Li M,* Chang H.* A human-specific schizophrenia risk tandem repeat affects alternative splicing of a human-unique isoform AS3MTd2d3 and mushroom dendritic spine density. Schizophrenia Bulletin 2021; 41(1):219-227.

7.        Li W,# Cai X,# Li HJ,# Song M,# Zhang CY, Yang Y, Zhang L, Zhao L, Liu W, Wang L, Shao M, Zhang Y, Zhang C, Cai J, Zhou DS, Li X, Hui L, Jia QF, Qu N, Zhong BL, Zhang SF, Chen J, Xia B, Li Y, Song X, Fan W, Tang W, Tang W, Tang J, Chen X, Yue W, Zhang D, Fang Y, Xiao X, Li M,* Lv L,* Chang H.* Independent replications and integrative analyses confirm TRANK1 as a susceptibility gene for bipolar disorder. Neuropsychopharmacology 2021; DOI:10.1038/s41386-020-00788-4.

8.        Yang Z,# Zhou D,# Li H,# Cai X, Liu W, Wang L, Chang H, Li M,* Xiao X.* The genome-wide risk alleles for psychiatric disorders at 3p21.1 show convergent effects on mRNA expression, cognitive function and mushroom dendritic spine. Molecular Psychiatry 2020; 25(2):48-66.

9.        Li H, Zhang C, Cai X, Wang L, Luo F, Ma Y, Li M,* Xiao X.* Genome-wide association study of creativity reveals genetic overlap with psychiatric disorders, risk tolerance, and risky behaviors. Schizophrenia Bulletin 2020; 46(5):1317-1326.

10.    Liu W,# Li W,# Cai X,# Yang Z,# Li H, Su X, Song M, Zhou DS, Li X, Zhang C, Shao M, Zhang L, Yang Y, Zhang Y, Zhao J, Chang H, Yao YG, Fang Y, Lv L,* Li M,* Xiao X.* Identification of a functional human-unique 351-bp Alu insertion polymorphism associated with major depressive disorder in the 1p31.1 GWAS risk loci. Neuropsychopharmacology 2020; 45(7):1196-1206.

11.    Li HJ,# Qu N,# Hui L,# Cai X, Zhang CY, Zhong BL, Zhang SF, Chen J, Xia B, Wang L, Jia QF, Li W, Chang H, Xiao X,* Li M,* Li Y.* Further confirmation of netrin 1 receptor (DCC) as a depression risk gene via integrations of multi-omics data. Translational Psychiatry 2020; 10(1):98.

12.    Zhou D, Xiao X, Li M.* The schizophrenia risk isoform ZNF804AE3E4 affects dendritic spine. Schizophrenia Research 2020; 218:324-325.

13.    Li HJ,# Su X,# Zhang L,# Zhang CY, Wang L, Li W, Yang Y, Lv L, Li M,* Xiao X.* Transcriptomic analyses of humans and mice provide insights into depression. Zoological Research 2020; 41(6):632-643..

14.    Yang ZH,# Cai X,# Qu N,# Zhao LJ, Zhong BL, Zhang SF, Chen J, Xia B, Jiang HY, Zhou DY, Liu WP, Chang H, Xiao X, Li Y,* Li M.* Identification of a functional 339 bp Alu insertion polymorphism in the schizophrenia-associated locus at 10q24.32. Zoological Research 2020; 41(1):84-89.

15.    Hu Z,* Xiao X, Zhang Z, Li M.* Genetic insights and neurobiological implications from NRXN1 in neuropsychiatric disorders. Molecular Psychiatry 2019; 24(10):1400-1414.

16.    Li H,# Chang H,# Song X,# Liu W, Li L, Wang L, Yang Y, Zhang L, Li W, Zhang Y, Zhou DS, Li X, Zhang C, Fang Y, Sun Y, Dai JP, Luo XJ, Yao YG, Xiao X,* Lv L,* Li M.* Integrative analyses of major histocompatibility complex loci in the genome-wide association studies of major depressive disorder. Neuropsychopharmacology 2019; 44(9):1552-1561.

17.    Liu W,# Yan H,# Zhou D,# Cai X,# Zhang Y, Li S, Li H, Li S, Zhou DS, Li X, Zhang C, Sun Y, Dai JP, Zhong J, Yao YG, Luo XJ, Fang Y, Zhang D, Ma Y, Yue W,* Li M,* Xiao X.* The depression GWAS risk allele predicts smaller cerebellar gray matter volume and reduced SIRT1 mRNA expression in Chinese population. Translational Psychiatry 2019; 9(1):333.

18.    Li H,# Zhou DS,# Chang H,# Wang L, Liu W, Dai SX, Zhang C, Cai J, Liu W, Li X, Fan W, Tang W, Tang W, Liu F, He Y, Bai Y, Hu Z, Xiao X, Gao L,* Li M.* Interactome analyses implicated CAMK2A in the genetic predisposition and pharmacological mechanism of bipolar disorder. Journal of Psychiatric Research 2019; 115:165-175.

19.    Xiao X, Zhang C,* Grigoroiu-Serbanescu M,* Wang L, Li L, Zhou D, Yuan T-F, Wang C, Chang H, Wu Y, Li Y, Wu D-D, Yao Y-G, Li M.* The cAMP responsive element-binding (CREB)-1 gene increases risk of major psychiatric disorders. Molecular Psychiatry 2018; 23(9):1957-1967.

20.    Chang H,# Hoshina N,# Zhang C,# Ma Y, Cao H, Wang Y, Wu DD, Bergen SE, Landén M, Hultman CM, Preisig M, Kutalik Z, Castelao E, Grigoroiu-Serbanescu M, Forstner AJ, Strohmaier J, Hecker J, Schulze TG, Müller-Myhsok B, Reif A, Mitchell PB, Martin NG, Schofield PR, Cichon S, Nothen MM, The Swedish Bipolar Study Group, MooDS Bipolar Consortium, Walter H, Erk S, Heinz A, Amin N, van Duijn CM, Meyer-Lindenberg A, Tost H, Xiao X, Yamamoto T,* Rietschel M,* Li M.* The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders. Molecular Psychiatry 2018; 23(2):400-412.

21.    Xiao X,# Zheng F,# Chang H, Ma Y, Yao YG, Luo XJ, Li M.* The gene encoding protocadherin 9 (PCDH9), a novel risk factor for major depressive disorder. Neuropsychopharmacology 2018; 43(5):1128-1137.

22.    Zhao L,# Chang H,# Zhou DS,# Cai J, Fan W, Tang W, Tang W, Li X, Liu W, Liu F, He Y, Bai Y, Sun Y, Dai J, Li L, Xiao X,* Zhang C,* Li M.* Replicated associations of FADS1, MAD1L1, and a rare variant at 10q26.13 with bipolar disorder in Chinese population. Translational Psychiatry 2018; 8(1):270.

23.    Chang H,# Xiao X,# Li M.* The schizophrenia risk gene ZNF804A: clinical associations, biological mechanisms and neuronal functions. Molecular Psychiatry 2017; 22(7):944-953.

24.    Xiao X, Wang L, Wang C, Yuan TF, Zhou D, Zheng F, Li L, Grigoroiu-Serbanescu M, Ikeda M, Iwata N, Takahashi A, Kamatani Y, Kubo M, Preisig M, Kutalik Z, Castelao E, Pistis G, Amin N, van Duijn CM, Forstner AJ, Strohmaier J, Hecker J, Schulze TG, Müller-Myhsok B, Reif A, Mitchell PB, Martin NG, Schofield PR, Cichon S, Nothen MM, Chang H, Luo XJ, Fang Y, Yao YG, Zhang C, Rietschel M, Li M;* Advanced Collaborative Study of Mood Disorder (COSMO) Team, MooDS Bipolar Consortium. Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders. Translational Psychiatry 2017; 7(12):1273.

25.    Li M, Jaffe AE, Straub RE, Tao R, Shin JH, Wang Y, Chen Q, Li C, Jia Y, Ohi K, Maher BJ, Brandon NJ, Cross A, Chenoweth J, Hoeppner DJ, Wei H, Hyde TM, McKay R, Kleinman JE, Weinberger DR.* A human-specific AS3MT isoform and BORCS7 are molecular risk factors in the 10q24.32 schizophrenia associated locus. Nature Medicine 2016; 22(6):649-656.

26.    Li M,* Chang H, Xiao X. BDNF Val66Met polymorphism and bipolar disorder in European populations: a risk association in case-control, family-based and GWAS studies. Neuroscience and Biobehavioral Reviews 2016; 68:218-233.

27.    Li M,#,* Wu DD,# Yao YG, Huo YX, Liu JW, Su B, Chasman DI, Chu AY, Huang T, Qi L, Zheng Y, CHARGE Nutrition Working Group, DietGen Consortium, Luo XJ.#,* Recent positive selection drives the expansion of a schizophrenia risk non-synonymous variant at SLC39A8 in Europeans. Schizophrenia Bulletin 2016; 42(1):178-190.

28.    Li M,#,* Luo XJ,# Landén M, Bergen SE, Hultman CM, Li X, Zhang W, Yao YG, Zhang C, Liu J, Mattheisen M, Cichon S. Mühleisen TW, Degenhardt FA, Nothen MM, Schulze TG, Grigoroiu-Serbanescu M, Li H, Fuller CK, Chen C, Dong Q, Chen C, Jamain S, Leboyer M, Bellivier F, Etain B, Kahn JP, Henry C, Preisig M, Kutalik Z, Castelao E, Wright A, Mitchell PB, Fullerton JM, Schofield PR, Montgomery GW, Medland SE, Gordon SD, Martin NG, MooDS Consortium, The Swedish Bipolar Study Group, Rietschel M, Liu C, Kleinman JE, Hyde TM, Weinberger DR, Su B.* Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance. British Journal of Psychiatry 2016; 208(2):128-137.

29.    Li M,# Luo XJ,# Rietschel M, Lewis CM, Mattheisen M, Müller-Myhsok B, Jamain S, Leboyer M, Landén M, Thompson PM, Cichon S, Nothen MM, Schulze TG, Sullivan PF, Bergen SE, Donohoe G, Morris DW, Hargreaves A, Gill M, Corvin A, Hultman C, Toga AW, Shi L, Lin Q, Shi H, Gan L, Meyer-Lindenberg A, Czamara D, Henry C, Etain B, Bis JC, Ikram MA, Fornage M, Debette S, Launer LJ, Seshadri S, Erk S, Walter H, Heinz A, Bellivier F, Stein JL, Medland SE, Vasquez AA, Hibar DP, Franke B, Martin NG, Wright MJ, MooDS Bipolar Consortium, The Swedish Bipolar Study Group, Alzheimer’ s Disease Neuroimaging Initiative, ENIGMA consortium, CHARGE consortium, Su B.* Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility. Molecular Psychiatry 2014; 19(4):452-461.

30.    Li M, Ge T, Feng J, Su B.* SLC6A15 rs1545843 and depression: implications from brain imaging data. American Journal of Psychiatry 2013; 170(7):805.

31.    Li M, Luo XJ, Xiao X, Shi L, Liu XY, Yin LD, Diao HB, Su B.* Allelic differences between Han Chinese and Europeans for functional variants in ZNF804A and their association with schizophrenia. American Journal of Psychiatry 2011; 168(12):1318-1325.

  研究团队

工作人员常宏(副研究员);肖潇(副研究员);王路(实验师)

研究生蔡欣;杨智辉;周丹阳;孙晨婧;张楚祎;尹美钰;张悦;丁忠莉

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