代表性成果

成果简介


1.阐明孤独症关键致病因子的功能及致病机制

通过自主构建孤独症关键致病因子的基因编辑动物模型,揭示了FOXG1Neurexin/NeuroliginROCK/PAK/LIMK等致病因子或信号通路在大脑模式形成、神经元命运决定和发生、神经元迁移和轴突投射、突触形成和通常可塑性等过程中的作用,揭示了上述致病因子和信号通路异常导致孤独症的机制,对阐明儿童孤独症的发病机制及相应诊治具有重要意义。


2. 多基因协同促进内耳干细胞再生重建听觉功能

研究了WntFoxG1Spectrin等基因在内耳干细胞增殖分化、毛细胞成熟和存活中的作用机制;优化了高效转染内耳干细胞的新型腺相关病毒, 建立了小鼠内耳干细胞的基因治疗系统。研究了多种生物材料和电、磁等物理刺激对听觉神经元再生、功能成熟和存活的调控机制。开创性地研究了自噬和免疫系统促进毛细胞和神经元存活的作用和机制。


3.揭示本能行为和学习记忆的分子与神经环路机制

阐明了生物节律通过特异性节律输出分子Fbxl4调控睡眠的分子细胞机制,揭示生物节律调控睡眠行为的作用机制。阐明机体在睡眠和求偶两种本能行为间抉择的机制,揭示了睡眠与求偶行为在神经环路上的相互作用。发现PKCλPKMζ分别在学习记忆的早期表达、巩固及后期维持阶段的作用,揭示一种存在于胞体的调节突触传入的细胞新机制。


4.揭示干细胞命运决定及重编程的转录调控机制

发现锌指蛋白ZFP281募集AFF3到增强子上精确调控印记基因的差异性表达,以及协同甲基转移酶MLL2调控转座子LINE-1区的组蛋白修饰以及染色质局部结构,调控干细胞的命运决定及重编程。揭示SEC介导多价相分离调控RNA聚合酶II转录暂停释放,从全新角度阐明基因快速协调转录激活程序的机制,为探索SEC相关疾病的机制及筛选靶向药物提供了新思路。


5. 原发性胆汁性胆管炎发病机制的研究

通过对汉族人群原发性胆汁性胆管炎(PBC)易感基因的研究,在国际上首次发现IL-21信号通路和T细胞辅助激活的异常在PBC发病机制中的重要作用,并通过CD58易感基因的发现把胆汁上皮细胞相关基因功能和PBC发病机制结合起来,为进一步探讨PBC发病机制提供了线索。


序号

论文题目

第一作者

通讯作者

刊物名称

发表时间

代表性成果

1

Neuroligin 1 regulates spines and synaptic plasticity via LIMK1.cofilin-mediated actinreorganization

刘安

谢维;加正平

The Journal of Cell Biology

201602

1

2

p21-activated kinase 1 restricts tonic endocannabinoid signaling in the hippocampus

夏淑婷

谢维;加正平

eLife

201606

1

3

Mutations of PQBP1 in Renpenning syndrome promote ubiquitin-mediated degradation of FMRP and cause synaptic dysfunction

张晓艳

张子超

Hum Mol Genet

201703

1

4

Neurexin Restricts Axonal Branching in Columns by Promoting Ephrin Clustering

刘丽娜

韩俊海

Dev Cell

201704

1

5

Proteolytic cleavage is required for Neuroligin 2 maturation and function in Drosophila

屠仁军

谢维

J Mol Cell Biol

201706

1

6

Neurexin-Neuroligin 1 regulates synaptic morphology and functions via the WAVE regulatory complex in Drosophila neuromuscular junction

邢广林

谢维;加正平

Elife

201803

1

7

HNRNPA1-induced spliceopathy in a transgenic mouse model of myotonic dystrophy

李默怡

谢维;李默怡

Proc Natl Acad Sci U S A. 2020,117(10): 5472-5477.

202003

1

8

Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea

刘丽曼,陈岩

柴人杰

Cell Death & Disease

201603

2

9

Accelerating bioelectric functional development of neural stem cells by graphene coupling: Implications for neural interfacing with conductive materials

郭荣荣

柴人杰;唐明亮

Biomaterials

201611

2

10

Autophagy protects auditory hair cells against neomycin-induced damage

贺祖宏

柴人杰

Autophagy

201710

2

11

Critical role of spectrin in hearing development and deafness

刘艳

柴人杰

Science Advances

201904

2

12

Wnt Signaling Activates TP53-Induced Glycolysis and Apoptosis Regulator and Protects Against Cisplatin-Induced Spiral Ganglion Neuron Damage in the Mouse Cochlea

刘闻闻

柴人杰

Antioxidants & Redox Signaling

201904

2

13

AAV-ie enables safe and efficient gene transfer to inner ear cells

谈方志

柴人杰

Nature Communications

201908

2

14

A cytoskeleton structure revealed bysimaging in inner ear hair cells.

齐洁玉

柴人杰

Cell Discovery

201909

2

15

Stress-Induced Metabolic Disorder in Peripheral CD4(+) T Cells Leads to Anxiety-like Behavior

范柯琪

柴人杰

Cell

201910

2

16

The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways.

贺祖宏

柴人杰

Redox Biology

202001

2

17

Isolation and analysis of extra cellular vesicles in a Morpho butterfly wing-integrated micro vortex biochip.

韩善颍

柴人杰

Biosensors and Bioelectronics

202004

2

18

Knock-down of Foxg1 in Supporting Cells Increases the Transdifferentiation of Supporting Cells into Hair Cells in the Neonatal Mouse Cochlea.

张莎莎

柴人杰

Cellular and Molecular Life Sciences

202004

2

19

Distinct roles of PKCι.λ and PKMζ in the initiation and maintenance of hippocampal long-term potentiation and memory

王韶莉

陆巍

Cell Rep

201608

3

20

Learning-induced suboptimal compensation for PKCι.λ function in mutant mice

盛涛

陆巍

Cerebral Cortex

201706

3

21

Genetic and neuronal mechanisms governing the sex-specific interaction between sleep and sexual behaviors in Drosophila

陈丹丹

潘玉峰

Nature communications

201707

3

22

Fbxl4 Serves as a Clock Output Molecule that Regulates Sleep through Promotion of Rhythmic Degradation of the GABA(A) Receptor

李倩

韩俊海

Curr Biol

201712

3

23

Drosulfakinin signaling in fruitless circuitry antagonizes P1 neurons to regulate sexual arousal in Drosophila

吴顺凡

潘玉峰

Nature communications

201910

3

24

Sex and Death: Identification of
 Feedback Neuromodulation Balanci
ng Reproduction and Survival

高灿

潘玉峰

Neuroscience Bulletin

202001

3

25

Long-Lasting Somatic Modifications of Convergent Dendritic Inputs in Hippocampal Neurons

杨鑫

陆巍

Cerebral Cortex, 2020,30: 1436–1446

202003

3

26

Enhancer, epigenetics and human diseases

罗卓娟

林承棋

Curr Opin Genet Dev

201602

4

27

A permissive chromatin state regulated by ZFP281-AFF3 in controlling the imprinted Meg3 polycistron

王艳

林承棋

Nucleic Acids Res

201702

4

28

Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells

戴倩

林承棋

Nucleic Acids Res

201712

4

29

AFF3-DNA methylation interplay in maintaining mono-allelic expression of XIST in terminally differentiated cells

张悦

罗卓娟

Journal of Molecular and Cell Biology

201909

4

30

ENL initiates multivalent phase separation of the super elongation complex (SEC) in controlling rapid transcriptional activation

郭澄豪

林承棋

Science Advances  2020,6(14)

202004

4

31

A genome-wide association study identifies six novel risk loci for primary biliary cholangitis

邱方

刘向东

Nature Communication

201704

5

32

Bidirectional regulation of fragile X mental retardation protein phosphorylation controls rhodopsin homoeostasis

王晓

韩俊海

JOURNAL OF M
OLECULAR CELL
 BIOLOGY

201704

5

33

Genome wide association studies of specific antinuclear autoantibody subphenotypes in primary biliary cholangitis

王婵

刘向东

Hepatology

201907

5

34

Fine Mapping of the MHC Region Identifies Major Independent Variants Associated With Han Chinese Primary Biliary Cholangitis

王婵

刘向东

Journal of autoimmunity 2020,107

202002

5



5