師資
個人簡介
劉東實驗室現有的兩個研究主題是:1)比較器官發育與再生的異同;2)建立人類疾病的動物模型。劉東博士長期從事硬骨魚類生物學研究,涉足發育、分子遺傳學(斑馬魚和日本青鳉),分子內分泌學(太平洋鮭鱒),轉基因(鯉科魚)、基因編輯技術(斑馬魚)等領域。我們主要是用模式動物斑馬魚研究動感毛細胞(mechanosensory hair cells)發育及其損傷-再生機制,并在建立神經性疾病模型基礎上研發治療性或預防性藥物。此外,運用線蟲的優勢,我們還在探索研究器官發育與再生的新思路、新方法。
研究領域
1. 斑馬魚內耳(外周神經系統器官)的發育機制
2. 斑馬魚側線毛細胞損傷/再生機制
3. 構建人類神經性疾病的斑馬魚模型,并進行治療性先導化合物的篩選,靶標確定及作用機理研究
4. 基因組編輯技術研發
具體研究內容
1. 斑馬魚內耳的發育:通過遺傳學和條件性調控基因表達等手段,已初步揭開從前基板區(一種在體干細胞群)到內耳細胞命運獲得的發育途徑,詮釋內耳功能細胞(內耳神經元和動感受體毛細胞)命運決定和維持的調控網絡
2. 斑馬魚側線毛細胞損傷/再生:位于斑馬魚體表的側線神經丘是毛細胞損傷/再生研究的好模型。通過突變體篩選,活體細胞分選和基因表達調控技術,已初步確定信號通路,轉錄因子和死亡程序與毛細胞再生現象間的關聯性。
3. 人類疾病的斑馬魚模型:已建立耳聾,多動癥和帕金森模型,并初選治療性先導化合物。
4. 新技術、新方向:已開發出鑒定有功能非蛋白編碼RNA,CRISPR/Cas9 基因編輯,dCas9 融合系統,亞細胞定位等技術;生殖細胞與體細胞性別發育的關聯研究。
工作經歷
2017-至今 南方科技大學生物系,副教授
2008-2017 北京大學生命科學學院,研究員, 博士生導師
1999-2008 俄勒岡大學神經所,博士后轉高級助研(senior research associate)
1990-1991 淡水生態學及生物技術國家重點實驗室(中科院武漢水生所),助研(research assistant)
教育背景
1999-2004 俄勒岡大學神經所,發育生物學博士后
1992-1999 多倫多大學生化系,分子內分泌學碩士、博士(PhD,哲學博士)
1987-1990 中國科學院水生生物研究所,遺傳學碩士
1983-1987 武漢大學生物系,理學學士
獲獎情況及榮譽
1. Travel Award, International Zebrafish Society, 2017(國際斑馬魚協會)
2. Roche Fellowship Award, School of Life Sciences, PKU 2012 (羅氏獎教金)
3. Peking University Talents Program, 2008-2011 (北京大學引進人才)
4. Hundred Talent Program nominee, Institute of Hydrobiology, the Chinese Academy of Sciences, 2008 (declined)
5. Hundred Talent Program nominee, Institute of Genetics and Developmental Biology, the Chinese Academy of Sciences, 2004(declined)
6. Travel Award, Society of Chinese Bioscientists in America, 2004 (美洲華人生物科學者協會)
7. Travel award, Association for Research in Otolaryngology, 2003 (美國耳鼻喉科研究協會)
8. Postdoctoral Fellowship, Canadian Institutes of Health Research, 2000 -2003 (加拿大健康研究院)
9. JSPS Postdoctoral Fellowship, 1999-2001(日本學術振興學會)(declined)
10. Restracom Trainee Fellowship, HSC, Toronto, 1994 -1999 (加拿大病童醫院研究所)
11. University of Toronto Open Fellowship, 1991-1992(多倫多大學)
獲資助情況
1. Principal Investigator, Establishing a new model of mechanosensory hair cell damage/regeneration (斑馬魚動感毛細胞損傷/再生新模型的建立), a NSFC regular grant (2018-2021).
2. Principal Investigator, Dlx3b-4b and Gata3 regulate otic hair cell development in zebrafish (Dlx3b-4b和Gata3是斑馬魚內耳毛細胞發育的主要調節因子), a NSFC regular grant (2016-2019).
3. Principal Investigator, Systematic characterization and analysis of tissue/cell-specific lincRNAs in elegans (系統性鑒定和分析線蟲組織/細胞特異(基因間區長片段非編碼RNA), a NSFC regular grant (2014-2017).
4. Principal Investigator, Developing new techniques for organ regeneration study, part of a MOST 973 Program (2012-2016). (第三課題組長)
5. Co-Principal Investigator, In vivo functional study of lincRNAs, part of a MOST 973 Program (2011-2015). (骨干PI)
6.Principal Investigator, Epigenetic regulation of sex differentiation and reproductive development(性別分化及生殖發育的表觀遺傳調控研究), a NSFC regular grant (2010-2012, ‘細胞編程與重編程的表觀遺傳機制’重大研究計劃).
NSFC:國家自然科學基金委;MOST:中華人民共和國科學技術部
代表文章(*:通訊或共同通訊作者)
1. Li J, Liu Y, Qin L, Huang X, Zhou D, Xu H, Zhao F, Mi X, Jia F, Xu F, Yang J, Li C, Liu D, Deng X, Zhang Y. (2017). Mutation in ε-sarcoglycan induces myoclonus dystonia syndrome by increasing the numbers of excitatory synapses. Submitted.
2. Wu YT, Mi X, Guo H, Zhao F, Zhang Y, Tang G, Yu K, Zhao J, Su X, Zhu Z, Raible DW, Liu D*. (2017). Regenerating neuromast hair cells directly from proliferative supporting cells in zebrafish. Revised
3. Li X, Song G, Zhao Y, Zhao F, Liu C, Liu D*, Li Q*, Cui Z*. (2017). Claudin7b is required for the formation and function of inner ear in zebrafish. J Cell Physiol (doi: 10.1002/jcp.26162. [Epub ahead of print]).
4. Yang L, Chang S, Lu Q, Zhang Y, Wu Z, Sun X, Cao Q, Qian Y, Jia T, Xu B, Duan Q, Li Y., Zhang K, Schumann G, Liu D*, Wang J*, Wang Y*, Lu L.(2017). A new locus regulating MICALL2 expression was identified for association with executive inhibition in children with attention deficit hyperactivity disorder. Mol Psychiatry(doi:10.1038/mp.2017.74).
5. Gao H, Bu Y, Wu Q, Wang X, Chang N, Lei L, Chen S, Liu D, Zhu X, Hu K, Xiong J. (2015). Mecp2 regulates neural cell differentiation by suppressing the Id1-Her2/Hes5 axis in zebrafish. J Cell Sci, 128(12):2340-2350.
6. Long L, Guo H, Yao D, Xiong K, Li Y, Liu P*, Zhu Z, Liu D*. (2015). Regulation of transcriptionally active genes via the catalytically inactive Cas9 in elegans and D. rerio. Cell Res, 25:638-641.
7. Wang J, Zhao F, Wu Y, Wu YT, Yao D, Dong W, Zhao J, Zhu Z, Liu D*. (2015). Fgf signaling dependent Sox9a and Atoh1a regulate otic neural development in zebrafish. J Neuroscience, 35:234-244 (highlighted article).
8. Yao D, Zhao F, Wu Y, Wang J, Zhao J, Zhu Z, Liu D*. (2014). Dissecting the differentiation process of the pre-placodal ectoderm in zebrafish. Special issue ‘Sensory system: Development, Disease & Regeneration’, Dev Dyn, 243:1328-1337.
9. Liu P, Long L, Xiong K, Yu B, Chang N, Xiong J-W, Zhu Z, Liu D*. (2014). Heritable/Conditional Genome Editing in elegans using a CRISPR-Cas9 Feeding System. Cell Res, 24:886-889.
10. Sheehan-Rooney K, Swartz ME, Zhao F, Liu D, Eberhart JK. (2013). Ahsa1 and Hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR). Dis Model Mech, 6(5):1285-91.
11. Dong W, Yang Z, Yang F, Wang J, Zhuang Y, Xu C, Zhang B, Tian X*, Liu D*. (2012). Suppression of Rap1 impairs cardiac myofibril and conduction system in zebrafish. PLoS ONE, 7(11): e50960. Doi:10.1371/journal.pone.0050960.
12. Liu M, Liu P, Zhang L, Gao G, Zhang W, Zhu Z, Liu D*, Fan Q*. (2011). mir-35 is involved in control of intestine cell G1/S transition and germ cell proliferation in C. elegans. Cell Res, 21(11):1605-18.
13. Choy SW, Cheng CW, Lee ST, Li VWT, Hui MNY, Hui C, Liu D, Cheng SH. (2010). A cascade of irx1a and irx2a controls shh expression during retinogenesis. Dev Dyn, 239:3204-14.
14. Yan Y-L, Willoughby J, Liu D, Crump JG, Wilson C, Miller CT, Singer A, Kimmel C, Westerfield M, Postlethwait JH. (2005). A pair of Sox: distinct and overlapping functions of zebrafish Sox9 co-orthologs in craniofacial and pectoral fin development. Development, 132: 1069-83.
15. Hans S, Liu D, Westerfield M. (2004). Pax8 and Pax2a function synergistically in otic specification, downstream of the Foxi1 and Dlx3b transcription factors. Development, 131: 5091-02.
16. Liu D, Chu H, Maves L, Yan YL, Morcos PA, Postlethwait JH, Westerfield M. (2003). Fgf3 and Fgf8 dependent and independent transcription factors are required for otic placode specification. Development, 130: 2213-24.
17. Yan Y-L, Miller CT, Nissen R, Singer A, Liu D, Kirn A, Draper B, Willoughby J, Morcos PA, Amsterdam A, Chung B, Westerfield M, Haffter P, Hopkins N, Kimmel C and Postlethwait JH. (2002). Zebrafish sox9 gene required for cartilage morphogenesis. Development, 129: 5065-79.
18. Liu D, Chandy M, Lee SK, Le Dréan Y, Ando H, Xiong F, Woon Lee J, Hew CL. (2000). A zebrafish ftz-F1 (Fushi tarazu factor 1) homologue requires multiple subdomains in the D and E regions for its transcriptional activity. J Biol Chem, 2;275(22):16758-66.
19. Liu D, Le Dréan Y, Ekker M, Xiong F, Hew CL. (1997). Teleost FTZ-F1 homolog and its splicing variant determine the expression of salmon gonadotropin II beta gene. Mol Endocrinol,11(7):877-90.
20. Wong AO, Dréan Y, Liu D, Hu Z, Xiong F, Hew CL. (1996). Induction of Chinook Salmon Growth Hormone Promoter Activity by the Adenosine 3′,5′-Monophosphate (cAMP)-Dependent Pathway Involves Two cAMP-Response Elements with the CGTCA Motif and the Pituitary-Specific Transcription Factor Pit-1. Endocrinology, 137(5):1775-84.
21. Dréan Y, Liu D, Wong AO, Xiong F, Hew CL. (1996). Steroidogenic factor 1 and estradiol receptor act in synergism to regulate the expression of the salmon gonadotropin II beta subunit gene. Mol Endocrinol,10(3):217-29.
22. Liu D, Xiong F, Hew CL. (1995) Functional analysis of estrogen-responsive elements in Chinook salmon (Oncorhynchus tschawytscha) gonadotropin II beta subunit gene. Endocrinology, 136(8):3486-93.
23. Xiong F, Liu D, Dréan Y, Elsholtz HP, Hew CL. (1994). Differential recruitment of steroid hormone response elements may dictate the expression of the pituitary gonadotropin II beta subunit gene during salmon maturation. Mol Endocrinol, 8(6):782-93.
24. Xiong F, Liu D, Dréan Y, Hew CL. (1994). The Chinook salmon gonadotropin II beta subunit gene contains a strong minimal promoter with a proximal negative element. Mol Endocrinol, 8(6):771-81.
25. Xie Y, Liu D, Zou J, Li G, Zhu Z. (1993). Gene transfer via electroporation in fish. Aquaculture, 111(1-4):207-13.
課程
教授過的課程包括:本科生《發育生物學》,研究生《細胞死亡與衰老》和《脊椎動物形態發生》,研究生專題《神經發育與再生》。2017秋季開講《動物形態發生學》。
聯系方式
深圳市南山區西麗學苑大道1088號南方科技大學第一科研樓202室
郵編:518055
電話:0755 88018487
電子郵件:[email protected]