项目成员

Philipp Khaitovich,博士,研究员。

中国科学院上海生命科学研究院计算生物学研究所所长,比较生物学课题组组长;中央"外专千人计划"入选者;目前主要致力于人脑发育和衰老的分子机制和人脑的进化机制两方面的研究。

Philipp Khaitovich教授1994年和1999年在俄罗斯莫斯科国立大学和美国伊利诺伊大学芝加哥分校先后获得生物学学士和博士学位;1999年至2012年先后在美国伊利诺伊大学芝加哥分校,德国马普进化人类学研究所从事科研工作;2006年获得德国马普学会青年科学家小组资助;2011年获马普进化人类学研究所教授职位;2012年9月起受聘中国科学院上海生命科学研究院。

Philipp Khaitovich教授的研究工作主要聚焦在两个方向:

1.人脑发育和衰老的分子机制

研究人脑从发育到衰老过程中转录组(包含mRNA,miRNA,ncRNA)、代谢组、蛋白组的变化以及变化调控机制。已初步从转录组水平上建立了人脑从发育到衰老的八种主要变化模型。之后将进一步通过测量并比较多组学数据,建立人脑发育衰老过程的分子变化基准图,并通过调控网络研究鉴定发育衰老过程中的关键调控因子,该研究将为实现人类健康衰老提供理论基础。

2.人脑的进化机制

通过比较人类、黑猩猩和猕猴不同脑部区域发育衰老全过程中转录组、代谢组、蛋白组等多种分子水平的变化,鉴定人脑特有的分子变化并据此揭示人脑特有功能进化机制。已发现人类大脑皮质在代谢组和转录组水平上的加速进化现象,并首次提出了人脑进化可能起源于皮质突触发育延迟。之后将进一步鉴定并比较人类更多脑部区域的特有分子变化特征,并通过比对认知能力紊乱相关疾病患者脑部中的多组学数据,全面解析作用于人脑发达认知能力形成下的进化机制。

代表论著:

1. Hu HY, He L, Fominykh K, Yan Z, Guo S, Zhang X, Taylor MS, Tang L, Li J, Liu J, Wang W, Yu H, Khaitovich P. (2012) Evolution of the human-specific microRNA miR-941. Nat Commun.2012 Oct 23;3:1145. doi: 10.1038/ncomms2146.

2. Han Y, Han D, Yan Z, Boyd-Kirkup JD, Green CD, Khaitovich P, Han JD. (2012) Stress-associated H3K4 methylation accumulates during postnatal development and aging of Rhesus macaque brain. Aging Cell. 2012 Sep 15. doi: 10.1111/acel.12007.

3. Weng K, Hu H, Xu AG, Khaitovich P, Somel M. (2012) Mechanisms of Dietary Response in Mice and Primates: A Role for EGR1 in Regulating the Reaction to Human-Specific Nutritional Content. PLoS One. 2012;7(8):e43915. Epub 2012 Aug 24.

4. Yuan Y, Chen YP, Boyd-Kirkup J, Khaitovich P, Somel M. (2012) Accelerated aging-related transcriptome changes in the female prefrontal cortex. Aging Cell. 2012 Jul 11. doi: 10.1111/j.1474-9726.2012.00859.x.

5. Khaitovich P. (2012) Layer cake: the first bite at gene expression diversity in the human brain. Genome Biol. 13(5):157

6. Khrameeva EE, Mironov AA, Fedonin GG, Khaitovich P, Gelfand MS. (2012) Spatial proximity and similarity of the epigenetic state of genome domains. PloS One.2012;7(4):e33947. Epub 2012 Apr 4

7. Liu X, Somel M, Tang L, Yan Z, Jiang X, Guo S, Yuan Y, He L, Oleksiak A, Zhang Y, Li N, Hu Y, Chen W, Qiu Z, Pääbo S, Khaitovich P. (2012) Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques. Genome Res, (2012-02-02)

8. Somel M, Liu X, Tang L, Yan Z, Hu H, Guo S, Jiang X, Zhang X, Xu G, Xie G, Li N, Hu Y, Chen W, Pääbo S, Khaitovich P. (2011) MicroRNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates. PLoS Biol. 9(12): e1001214.

9. Brawand D, Soumillon M, Necsulea A, Julien P, Csárdi G, Harrigan P, Weier M, Liechti A, Aximu-Petri A, Kircher M, Albert FW, Zeller U, Khaitovich P, Grutzner F, Bergmann S, Nielsen R, Pääbo S, Kaessmann H. (2011) The evolution of gene expression levels in mammalian organs. Nature Oct 19;478(7369):343-8.

10. Hu HY, Guo S, Jiang X, Yan Z, Fu Ning, Zhang X, Menzel C, Liang H, Yang H, Zhao M, Zeng R, Chen W, Pääbo S, Khaitovich P. (2011) MicroRNA Expression and Regulation in Human, Chimpanzee, and Macaque Brains. PLoS Genetics. 7(10): e1002327.

11. Yuan Y, Chen YP, Ni S, Xu AG, Tang L, Vingron M, Somel M, Khaitovich P. (2011) Development and application of a modified dynamic time warping algorithm (DTW-S) to analyses of primate brain expresion time series. BMC Bioinformatics. 12(1):347

12. Jin C, Li J, Green CD, Yu X, Tang X, Han D, Xian B, Wang D, Huang X, Cao X, Yan Z, Hou L, Liu J, Shukeir N, Khaitovich P, Chen C D, Zhang H, Jenuwein T, Han JD. (2011) Histone Demethylase UTX-1 Regulates C. elegans Life Span by Targeting the Insulin/IGF-1 Signaling Pathway. Cell Metabolism. 14(2):161-172.

13. Yan Z, Hu H, Jiang X, Maierhofer V, Neb E, He L, Hu Y, Hu H, Li N, Chen W and Khaitovich P. (2011) Widespread expression of piRNA-like molecules in somatic tissues. Nucleic Acids Research. May 5.

14. Fu X, Giavalisco P, Liu X, Catchpole G, Fu N, Ning ZB, Guo S, Yan Z, Somel M, Pääbo S, Zeng R, Willmitzer L, Khaitovich P. (2011) Rapid metabolic evolution in human prefrontal cortex.Proc Natl Acad Sci U S A. Mar 28.

15. Somel M, Guo S, Fu N, Yan Z, Hu HY, Xu Y, Yuan Y, Ning Z, Hu Y, Menzel C, Hu H, Lachmann M, Zeng R, Chen W, Khaitovich P. (2010) MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome Res 20(9):1207-18.

16. Xu AG, He L, Li Z, Xu Y, Li M, Fu X, Yan Z, Yuan Y, Menzel C, Li N, Somel M, Hu H, Chen W, Pääbo S, Khaitovich P. (2010) Intergenic and repeat transcription in human, chimpanzee and macaque brains measured by RNA-Seq. PLoS Comput Biol 1;6:e1000843.

17. Shao NY, Hu HY, Yan Z, Xu Y, Hu H, Menzel C, Li N, Chen W, Khaitovich P. (2010) Comprehensive survey of human brain microRNA by deep sequencing. BMC Genomics11:409.

18. Khaitovich P. (2010) Annotating conserved and novel features of primate transcriptomes using sequencing. Genome Biol 11(7):125.

19. Hu HY, Yan Z, Xu Y, Hu H, Menzel C, Zhou YH, Chen W, Khaitovich P. (2009) Sequence features associated with microRNA strand selection in humans and flies. BMC Genomics10:413.

20. Fu X, Fu N, Guo S, Yan Z, Xu Y, Hu H, Menzel C, Chen W, Li Y, Zeng R, Khaitovich P. (2009) Estimating accuracy of RNA-Seq and microarrays with proteomics. BMC Genomics10(1):161

21. Somel M, Franz H, Yan Z, Lorenc A, Guo S, Giger T, Kelso J, Nickel B, Dannemann M, Bahn S, Webster MJ, Weickert CS, Lachmann M, Pääbo S, Khaitovich P. (2009) Transcriptional neoteny in the human brain. Proc Natl Acad Sci U S A 106(14):5743-8.

22. Khaitovich P, Lockstone HE, Wayland MT, Tsang TM, Jayatilaka SD, Guo AJ, Zhou J, Somel M, Harris LW, Holmes E, Pääbo S, Bahn S. (2008) Metabolic changes in schizophrenia and human brain evolution. Genome Biol. 9(8):R124.

23. Somel M, Creely H, Franz H, Mueller U, Lachmann M, Khaitovich P, Pääbo S. (2008) Human and chimpanzee gene expression differences replicated in mice fed different diets. PLoS ONE 3(1):e1504.

24. Khaitovich P. (2007) Brain expression--is it all in our SNPs? Mol Syst Biol. 3:155

25. Fu, N., Drinnenberg, I., Kelso, J., Wu, J.R., Paabo, S., Zeng, R., and Khaitovich, P. (2007). Comparison of protein and mRNA expression evolution in humans and chimpanzees. PLoS ONE 2, e216.

26. Somel, M., Khaitovich, P., Bahn, S., Paabo, S., and Lachmann, M. (2006). Gene expression becomes heterogeneous with age. Curr Biol 16, R359-360.

27. Khaitovich, P., Tang, K., Franz, H., Kelso, J., Hellmann, I., Enard, W., Lachmann, M., and Paabo, S. (2006). Positive selection on gene expression in the human brain. Curr Biol 16, R356-358.

28. Khaitovich, P., Kelso, J., Franz, H., Visagie, J., Giger, T., Joerchel, S., Petzold, E., Green, R.E., Lachmann, M., and Paabo, S. (2006). Functionality of intergenic transcription: an evolutionary comparison. PLoS Genet 2, e171.

29. Khaitovich, P., Enard, W., Lachmann, M., and Paabo, S. (2006). Evolution of primate gene expression. Nat Rev Genet 7, 693-702.

30. Creely, H., and Khaitovich, P. (2006). Human brain evolution. Prog Brain Res 158, 295-309.

31. Khaitovich, P., Paabo, S., and Weiss, G. (2005). Toward a neutral evolutionary model of gene expression. Genetics 170, 929-939.

32. Khaitovich, P., Hellmann, I., Enard, W., Nowick, K., Leinweber, M., Franz, H., Weiss, G., Lachmann, M., and Paabo, S. (2005). Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees. Science 309, 1850-1854.

33. Franz, H., Ullmann, C., Becker, A., Ryan, M., Bahn, S., Arendt, T., Simon, M., Paabo, S., andKhaitovich, P. (2005). Systematic analysis of gene expression in human brains before and after death. Genome Biol 6, R112.