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PHILIPP KAPRANOV, PhD

发布时间:2022-04-10 浏览次数:

1BBF4


Philipp Kapranov, Ph.D.

菲利普卡帕诺夫 博士

教授,博士生导师

基因组学研究所所长

国家级特聘专家

福建省百人计划特聘专家

福建省高校领军人才

福建省高端外专团队带头人

 话:0592-6167250

E-mail: philippk08@hotmail.com

 

Philipp Kapranov教授在非编码RNADNA损伤和核酶领域进行了一系列开创性的研究。2002年他发表了世界上第一个关于人类基因组中存在非编码RNA普遍转录现象(即基因组暗物质RNA”)的开创性工作(Kapranov et al, Science, 2002),改变了科学界对基因组中大量非编码区的垃圾基因看法。此后,他在ScienceNatureCellCNS 系列子刊、Genome ResearchGenome BiologyNucleic Acids Research等权威期刊发表了一系列论文进一步探讨了暗物质RNA”的复杂性、机制和功能。他的系列研究对非编码RNA研究工作发挥了重要的引领和推动作用,2010暗物质RNA”的发现被《科学》杂志评为过去十年中最重要的科学突破之一

近年来,他带领的课题组把研究交叉扩展到DNA损伤修复和核酶领域。在DNA损伤修复相关研究中,开发了行业内首个可应用于人类的单核苷酸分辨率DNA单链断裂检测方法——SSiNGLe(single-strand break mapping at nucleotide genome level),并绘制了第一张单核苷酸分辨率DNA单链断裂的全基因组图谱,解析了DNA的断裂位置与年龄增长而变化的新模式(Cao et al, Nature Communications, 2019)。在核酶相关研究中,通过开发全新的高通量方法在人类基因组中发现了一种全新类型的自切型核酶——hovlinc 核酶,这是首次在人类超长链基因间非编码RNAvlincRNA)中发现天然核酶Chen et al, Nature Chemical Biology, 2021),指出了长非编码RNAlncRNA)通过其中具有催化功能的RNA片段发挥功能的可能性和新思路。

目前他已发表同行评议论文90余篇,包括7Nature5Science2Cell以及12CNS子刊。在GoogleScholar中的总引用量45,449次、总H-index48i10-index77,第一作者或通讯作者单篇文章最高引用量为2500+次。

欢迎生物、医学、数理统计、计算机专业背景的学生报考硕博士生;也欢迎理工科相关专业学生有此类研究兴趣的跨专业申请。

 

研究领域(Research Areas)

 

Our group combines genomics, transcriptomics, next generation sequencing, bioinformatics and traditional molecular biology to discover the intricacies of molecular processes happening in our cells. Our research interests focus on three main directions:

1.   Discovery and functional characterization of novel transcripts and genes in the human genome with specific emphasis on long non-coding RNAs.

2.   Discovery and characterization of novel ribozymes in different organisms.

3.   Developing and applying high-resolution technologies to map DNA damage genome-wide and with high-resolution to study its effects on aging, cancer or other human diseases.

本课题组结合了基因组学、转录组学、下一代测序、生物信息学和传统分子生物学等研究手段来探索和发现人类细胞中发生的复杂的分子过程。我们的研究兴趣主要集中在以下三个方向:

1.    对人类基因组中的新转录本和基因,尤其是长非编码 RNA进行发现和功能表征。

2.    不同生物体新类型核酶的发现和表征。

3.    开发和应用高分辨率DNA 损伤检测技术,绘制全基因组范围高分辨率DNA 损伤图谱,研究DNA 损伤对衰老、癌症或其他人类疾病的影响机制。

 

 

代表性论文(Selected Publications).

 

1.    Chen Y, Qi F, Gao F, Cao H, Xu D, Salehi-Ashtiani K, Kapranov P. (2021) Hovlinc is a recently evolved class of ribozyme found in human lncRNA. Nature Chemical Biology 17:601-607

2.    Cao H, Xu D, Cai Y, Han X, Tang L, Gao F, Qi Y, Cai D, Wang H, Ri M, Antonets D, Vyatkin Y, Chen Y, You X, Wang F, Nicolas E, Kapranov P. (2021) Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans. BMC Biology 19:108.

3.    Gao F, Cai Y, Kapranov P, Xu D. (2020) Reverse-genetics studies of lncRNAs-what we have learnt and paths forward. Genome Biology 21:93.

4.    Xu D, Cai Y, Tang L, Han X, Gao F, Cao H, Qi F, Kapranov P. (2020) A CRISPR/Cas13-based approach demonstrates biological relevance of vlinc class of long non-coding RNAs in anticancer drug response. Scientific Reports 10:1794.

5.    Cao H, Salazar-García L, Gao F, Wahlestedt T, Wu CL, Han X, Cai Y, Xu D, Wang F, Tang L, Ricciardi N, Cai D, Wang H, Chin MPS, Timmons JA, Wahlestedt C, Kapranov P. (2019) Novel approach reveals genomic landscapes of single-strand DNA breaks with nucleotide resolution in human cells. Nature Communications 10:5799.

6.    Mouawad R, Prasad J, Thorley D, Himadewi P, Kadiyala D, Wilson N, Kapranov P, Arnosti DN. (2019) Diversification of Retinoblastoma Protein Function Associated with Cis and Trans Adaptations. Molecular Biology & Evolution 36:2790-2804.

7.    Diao Y, Rahman MF, Vyatkin Y, Azatyan A, St Laurent G, Kapranov P*, Zaphiropoulos PG. (2018) Identification of novel GLI1 target genes and regulatory circuits in human cancer cells. Molecular Oncology 12:1718-1734.

*co-corresponding author

8.    Cao H, Wahlestedt C, Kapranov P. (2018) Strategies to Annotate and Characterize Long Noncoding RNAs: Advantages and Pitfalls. Trends in Genetics 34:704-721.

9.    St Laurent G, Vyatkin Y, Antonets D, Ri M, Qi Y, Saik O, Shtokalo D, de Hoon MJ, Kawaji H, Itoh M, Lassmann T, Arner E, Forrest AR; FANTOM consortium, Nicolas E, McCaffrey TA, Carninci P, Hayashizaki Y, Wahlestedt C, Kapranov P. (2016) Functional annotation of the vlinc class of non-coding RNAs using systems biology approach. Nucleic Acids Research 44:3233-52.

10. Pastori C, Kapranov P, Penas C, Peschansky V, Volmar CH, Sarkaria JN, Bregy A, Komotar R, St Laurent G, Ayad NG, Wahlestedt C. (2015) The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation. Proc Natl Acad Sci U S A 112:8326-31

11. St Laurent G, Wahlestedt C, Kapranov P. (2015) The Landscape of long noncoding RNA classification. Trends in Genetics 3:239-51.

12. Lazorthes S, Vallot C, Briois S, Aguirrebengoa M, Thuret JY, Laurent GS, Rougeulle C, Kapranov P, Mann C, Trouche D, Nicolas E. (2015) A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus. Nature Communications 6:5971.

13. Savva YA, Jepson JE, Chang YJ, Whitaker R, Jones BC, St Laurent G, Tackett MR, Kapranov P, Jiang N, Du G, Helfand SL, Reenan RA (2013) RNA editing regulates transposon-mediated heterochromatic gene silencing. Nature Communications 4:2745

14. St. Laurent G, Tackett MR, Nechkin S, Shtokalo D, Antonets D, Savva YA, Maloney R, Kapranov P, Lawrence CE, Reenan RA (2013) Genome-Wide Analysis of A-to-I RNA Editing via Single Molecule Sequencing in Drosophila. Nature Structural & Molecular Biology 20:1333-9.

15. St Laurent G, Shtokalo D, Dong B, Tackett MR, Fan X, Lazorthes S, Nicolas E, Sang N, Triche TJ, McCaffrey TA, Xiao W, Kapranov P (2013) VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer. Genome Biology 14:R73.

16. Khare T, Pai S, Koncevicius K, Pal M, Kriukiene E, Zita Liutkeviciute Z, Irimia M, Jia P, Ptak C, Xia M, Tice R, Moréra S, Nazarians A, Belsham D, Wong AHC, Blencowe BJ, Wang SC, Kapranov P, Kustra R, Labrie V, Klimasauskas S, Petronis A (2012) 5-hmC in the brain: abundance in synaptic genes and differences at the exon-intron boundary. Nature Structural & Molecular Biology 19:1037-43.

17. ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57-74.

18. ENCODE Project Consortium (2012) Landscape of transcription in human cells. Nature 489:101-8.

19. Pastor WA, Pape UJ, Huang Y, Henderson HR, Lister R, Ko M, McLoughlin EM, Brudno Y, Mahapatra S, Kapranov P, Tahiliani M, Daley GQ, Liu XS, Ecker JR, Milos PM, Agarwal S, Rao A (2011) Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature 473:394-7.

20. Graveley BR, Brooks AN, Carlson JW, Duff MO, Landolin JM, Yang L, Artieri CG, van Baren MJ, Boley N, Booth BW, Brown JB, Cherbas L, Davis CA, Dobin A, Li R, Lin W, Malone JH, Mattiuzzo NR, Miller D, Sturgill D, Tuch BB, Zaleski C, Zhang D, Blanchette M, Dudoit S, Eads B, Green RE, Hammonds A, Jiang L, Kapranov P, Langton L, Perrimon N, Sandler JE, Wan KH, Willingham A, Zhang Y, Zou Y, Andrews J, Bickel PJ, Brenner SE, Brent MR, Cherbas P, Gingeras TR, Hoskins RA, Kaufman TC, Oliver B, Celniker SE. (2010) The developmental transcriptome of Drosophila melanogaster. Nature 471:473-9.

21. modENCODE Consortium (2010) Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science 330:1787-97.

22. Kapranov P*, Ozsolak F*, Kim SW*, Foissac F*, Huang J, Lipson D, Hart C, Roels S, Borel C, Antonarakis SE, Monaghan AP,  John B, Milos PM (2010) Novel class of human RNA species associated with gene termini suggests an uncharacterized RNA copying mechanism. Nature 466:642-6.

*equal contribution.

23. Ozsolak F, Kapranov P, Foissac S, Kim SW, Fishilevich E, Monaghan P, John B, Milos PMM (2010) Genome-wide Profiling of Polyadenylation Sites by Direct RNA Sequencing. Cell 143: 1018-1029.

24. Plessy C, Bertin N, Takahashi H, Simone R, Salimullah M, Lassmann T, Vitezic M, Severin J, Olivarius S, Lazarevich D, Hornig N, Orlando V, Bell I, Gao H, Dumais J, Kapranov P, Wang H, Davis CA, Gingeras TR, Kawai J, Daub CO, Hayashizaki Y, Gustincich S, Carninci P. (2010) Linking new promoters to functional transcripts in small samples with nanoCAGE and CAGEscan. Nature Methods 7:528-34.

25. Affymetrix/Cold Spring Harbor Laboratory ENCODE Transcriptome Project (2009)

Cold Spring Harbor Laboratory: Fejes-Toth K*, Sotirova V, Sachidanandam R, Assaf G, Hannon GJ;

Affymetrix: Kapranov P*, Foissac S, Willingham AT, Duttagupta R, Dumais E, Gingeras TR

Post-transcriptional processing generates a diversity of 5’-modified long and short RNAs. Nature 457:1028-32.

*equal contribution.

26. Djebali S*, Kapranov P*, Foissac S*, Lagarde J*, Reymond A*, Ucla C, Wyss C, Drenkow J, Dumais E, Murray RR, Lin C, Szeto D, Denoeud F, Vidal M, Calvo M, Salehi-Ashtiani K, Antonarakis SE, Gingeras TR, Guigó G (2008) Efficient targeted transcript discovery via array-based normalization of RACE libraries. Nature Methods 5:629-635.  

*equal contribution.

27. ENCODE Project Consortium. (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 447:799-816.

28. Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR. (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484-8.

29. Kapranov P, Willingham AT, Gingeras TR (2007). Genome-wide transcription and the implications for genomic organization. Nature Reviews Genetics 8:413-23.

30. Yang A, Zhu Z, Kapranov P, McKeon F, Church GM, Gingeras TR, Struhl K. (2006) Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells. Molecular Cell 24:593-602.

31. Manak JR, Dike S, Sementchenko V, Kapranov P, Biemar F, Long J, Cheng J, Bell I, Ghosh S, Piccolboni A, Gingeras TR. (2006) Biological function of unannotated transcription during the early development of Drosophila melanogaster. Nature Genetics 38:1151-1158.

32. Cheng J*, Kapranov P*, Drenkow J, Dike S, Brubaker S, Patel S, Long J, Stern D, Tammana H, Helt G, Sementchenko V, Piccolboni A, Bekiranov S, Kampa D, Madhavan G, Ghosh S, Bell I, Gerhard DS, Gingeras TR (2005) Transcriptional Maps of 10 Human Chromosomes at 5 Nucleotide Resolution. Science 308:1149-1154.

*equal contribution.

33. ENCODE Project Consortium (2004) The ENCODE (ENCyclopedia Of DNA Elements) Project. Science 306: 636-40.

34. Cawley S, Bekiranov S, Ng HH, Kapranov P, Sekinger EA, Kampa D, Piccolboni A, Sementchenko V, Cheng J, Williams AJ, Wheeler R, Wong B, Drenkow J, Yamanaka M, Patel S, Brubaker S, Tammana H, Helt G, Struhl K, Gingeras TR. (2004) Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 116:499-509.

35. Kapranov P, Cawley SE, Drenkow J, Bekiranov S, Strausberg RL, Fodor SPA, Gingeras TR (2002) Large-Scale Transcriptional Activity in Chromosomes 21 and 22. Science 296: 916-919.

 

期刊审稿人(Peer Review Activity:

- Nature

- Nature Biotechnology

- Nature Communications

- Nature Genetics

- PNAS

- Genome Biology

- Genome Research

- Nucleic Acids Research

- Molecular Cancer

- PLOS

- BMC Genomics

- Frontiers

- Scientific reports

- Gene

- Others…

期刊编辑(Editing of Professional Journals:

副主编, Frontiers in Genetics www.frontiersin.org