代表性成果

成果簡介

1.闡明孤獨症關鍵緻病因子的功能及緻病機制

通過自主構建孤獨症關鍵緻病因子的基因編輯動物模型，揭示了FOXG1、Neurexin/Neuroligin、ROCK/PAK/LIMK等緻病因子或信号通路在大腦模式形成、神經元命運決定和發生、神經元遷移和軸突投射、突觸形成和通常可塑性等過程中的作用，揭示了上述緻病因子和信号通路異常導緻孤獨症的機制，對闡明兒童孤獨症的發病機制及相應診治具有重要意義。

2. 多基因協同促進内耳幹細胞再生重建聽覺功能

研究了Wnt、FoxG1、Spectrin等基因在内耳幹細胞增殖分化、毛細胞成熟和存活中的作用機制；優化了高效轉染内耳幹細胞的新型腺相關病毒, 建立了小鼠内耳幹細胞的基因治療系統。研究了多種生物材料和電、磁等物理刺激對聽覺神經元再生、功能成熟和存活的調控機制。開創性地研究了自噬和免疫系統促進毛細胞和神經元存活的作用和機制。

3.揭示本能行為和學習記憶的分子與神經環路機制

闡明了生物節律通過特異性節律輸出分子Fbxl4調控睡眠的分子細胞機制，揭示生物節律調控睡眠行為的作用機制。闡明機體在睡眠和求偶兩種本能行為間抉擇的機制，揭示了睡眠與求偶行為在神經環路上的相互作用。發現PKCλ與PKMζ分别在學習記憶的早期表達、鞏固及後期維持階段的作用，揭示一種存在于胞體的調節突觸傳入的細胞新機制。

4.揭示幹細胞命運決定及重編程的轉錄調控機制

發現鋅指蛋白ZFP281募集AFF3到增強子上精确調控印記基因的差異性表達，以及協同甲基轉移酶MLL2調控轉座子LINE-1區的組蛋白修飾以及染色質局部結構，調控幹細胞的命運決定及重編程。揭示SEC介導多價相分離調控RNA聚合酶II轉錄暫停釋放，從全新角度闡明基因快速協調轉錄激活程序的機制，為探索SEC相關疾病的機制及篩選靶向藥物提供了新思路。

5. 原發性膽汁性膽管炎發病機制的研究

通過對漢族人群原發性膽汁性膽管炎（PBC）易感基因的研究，在國際上首次發現IL-21信号通路和T細胞輔助激活的異常在PBC發病機制中的重要作用，并通過CD58易感基因的發現把膽汁上皮細胞相關基因功能和PBC發病機制結合起來，為進一步探讨PBC發病機制提供了線索。

序号

論文題目

第一作者

通訊作者

刊物名稱

發表時間

代表性成果

1

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

劉安

謝維；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

謝維；加正平

eLife

201606

1

3

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

張曉豔

張子超

Hum Mol Genet

201703

1

4

Neurexin Restricts Axonal Branching in Columns by Promoting Ephrin Clustering

劉麗娜

韓俊海

Dev Cell

201704

1

5

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

屠仁軍

謝維

J Mol Cell Biol

201706

1

6

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

邢廣林

謝維；加正平

Elife

201803

1

7

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

李默怡

謝維；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

劉麗曼，陳岩

柴人傑

Cell Death & Disease

201603

2

9

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

郭榮榮

柴人傑；唐明亮

Biomaterials

201611

2

10

Autophagy protects auditory hair cells against neomycin-induced damage

賀祖宏

柴人傑

Autophagy

201710

2

11

Critical role of spectrin in hearing development and deafness

劉豔

柴人傑

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

劉聞聞

柴人傑

Antioxidants & Redox Signaling

201904

2

13

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

談方志

柴人傑

Nature Communications

201908

2

14

A cytoskeleton structure revealed bysimaging in inner ear hair cells.

齊潔玉

柴人傑

Cell Discovery

201909

2

15

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

範柯琪

柴人傑

Cell

201910

2

16

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

賀祖宏

柴人傑

Redox Biology

202001

2

17

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

韓善颍

柴人傑

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.

張莎莎

柴人傑

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

陸巍

Cell Rep

201608

3

20

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

盛濤

陸巍

Cerebral Cortex

201706

3

21

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

陳丹丹

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

韓俊海

Curr Biol

201712

3

23

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

吳順凡

潘玉峰

Nature communications

201910

3

24

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

高燦

潘玉峰

Neuroscience Bulletin

202001

3

25

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

楊鑫

陸巍

Cerebral Cortex, 2020,30: 1436–1446

202003

3

26

Enhancer, epigenetics and human diseases

羅卓娟

林承棋

Curr Opin Genet Dev

201602

4

27

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

王豔

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

張悅

羅卓娟

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

劉向東

Nature Communication

201704

5

32

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

王曉

韓俊海

JOURNAL OF M
OLECULAR CELL
 BIOLOGY

201704

5

33

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

王婵

劉向東

Hepatology

201907

5

34

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

王婵

劉向東

Journal of autoimmunity 2020,107

202002

5