User:Kun Zhang

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Kun Zhang, Ph.D.
Associate Professor
Department of Bioengineering
University of California, San Diego
9500 Gilman Drive, MC0412
La Jolla, CA 92903
Zhang Lab Website

Research Interests

We are developing genome technologies based on single-molecule sequencing, single-cell manipulation/amplification, and chip-based synthesis and manipulation of complex DNA libraries. We apply these novel technologies to stem cell genomics, personal genomes and human common diseases.


  1. Ruiz S*, Gore A*, Li Z, Panopoulos AD, Montserrat N, Fung HL, Giorgetti A, Bilic J, Batchelder EM, Zaehres H, Schöler HR, Zhang K, Izpisua Belmonte JC. (2013) Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming. Nature Communications, 4:1382, doi:10.1038/ncomms2381
  2. Yamaguchi S, Hong K, Liu R, Inoue A, Shen L, Zhang K, Zhang Y. (2013). Dynamics of 5-methylcytosine and 5-hydroxymethylcytosine during germ cell reprogramming. Cell Research (in press)
  3. Yamaguchi S*, Hong K*, Liu R*, Shen L, Inoue A, Diep D, Zhang K, Zhang Y. (2012) Tet1 controls meiosis by regulating meiotic gene expression. Nature, 492:443-7
  4. Michaelson JJ, Shi Y, Gujral M, Zheng H, Malhotra D, Jin X, Jian M, Liu G, Greer D, Bhandari A, Wu W, Corominas R, Peoples A, Koren A, Gore A, Kang S, Lin GN, Estabillo J, Gadomski T, Singh B, Zhang K, Akshoomoff N, Corsello C, McCarroll S, Iakoucheva LM, Li Y, Wang J, Sebat J. (2012) Whole-genome sequencing in autism identifies hot spots for de novo germline mutation. Cell 151:1431-42
  5. Panopoulos AD, Yanes O, Ruiz S, Kida Y, Diep D, Tautenhahn R, Herrerías A, Batchelder EM, Plongthongkum N, Lutz M, Berggren WT, Zhang K, Evans RM, Siuzdak G, Izpisua Belmonte JC. (2011) The metabolome of induced pluripotent stem cells reveals metabolic changes occuring in somatic cell reprogramming. Cell Research doi: 10.1038/cr.2011.177.
  6. Ruiz S*, Diep D*, Gore A, Panopoulosa AD, Montserratd N, Plongthongkum N, Kumara S, Fung HL, Giorgetti A, Bilic J, Batchelder EM, Zaehres H, Kan NG, Schöler HR, Mercola M, Zhang K, Belmonte JCI. (2012) Identification of a specific reprogramming-associated epigenetic signature in human induced pluripotent stem cells. Proc Natl Acad Sci USA. 109:16196-201
  7. Lachance J, Vernot B, Elbers CC, Ferwerda B, Froment A, Bodo JM, Lema G, Fu W, Nyambo TB, Rebbeck TR, Zhang K, Akey JM, Tishkoff SA. (2012) Evolutionary history and adaptation from high-coverage whole-genome sequences of diverse african hunter-gatherers. Cell, 150:457-69
  8. Ball MP, Thakuria JV, Zaranek AW, Clegg T, Rosenbaum AM, Wu X, Angrist M, Bhak J, Bobe J, Callow M, Cano C, Chou MF, Chung WK, Douglas SM, Estep P, Gore A, Hulick P, Labarga A, Lee J, Lunshof J, Kim BC, Kim JI, Li Z, Murray MF, Nilsen GB, Peters B, Raman AM, Reinhoff HY, Robasky K, Wheeler M, Vandewege W, Vorhaus D, Yang JL, Yang L, Aach J, Ashley EA, Drmanac R, Kim SJ, Li JB, Peshkin L, Seidman CE, Seo JS, Zhang K, Rehm HL, Church GM (2012) A Public Resource Facilitating Clinical Use of Genomes. Proc Natl Acad Sci USA. 109:11920-7
  9. Diep D*, Plongthongkum N*, Gore A*, Fung HL, Shoemaker R, Zhang K. (2012) Library-free methylation sequencing with bisulfite padlock probes. Nature Methods, 9:270-2
  10. Noggle S, Fung HL, Gore A, Martinez H, Crumm C, Prosser R, Oum K, Paull D, Druckenmiller S, Freeby M, Greenberg E, Zhang K, Goland R, Sauer MV, Leibel RL, Egli D. (2011) Human oocytes reprogram somatic cells to a pluripotent state. Nature 478:70-5
  11. Lee EJ, Pei L, Srivastava G, Trupit J, Kushwaha G, Choi JH, Robertson K, Wang X, Colbourne J, Zhang L, Schroth G, Xu D, Zhang K, Shi H. (2011) Targeted bisulfite sequencing by solution hybrid selection and massively parallel sequencing. Nucleic Acids Research 10.1093/nar/gkr598.
  12. Chen CH, Cho SH, Chiang HI, Tsai F, Zhang K, Lo YH. (2011) Specific sorting of single bacterial cells with micro-FACS and tyramide signal amplification-FISH. Analytical Chemistry 83:7269-75
  13. Guo J, Ma D, Mo H, Ball MP, Jang MH, Bonaguidi MA, Balazer JA, Eaves HL, Xie B, Ford E, Zhang K, Ming GL, Gao Y, Song H. (2011) Neuronal activity modifies DNA methylation landscape in the adult brain. Nature Neuroscience, 14:1345-51
  14. Hansen KD, Timp W, Bravo HC, Sabunciyan S, Langmead B, McDonald OG, Wen B, Wu H, Liu Y, Diep D, Briem E, Zhang K, Irizarry RA, Feinberg AP. (2011) Increased methylation variation in epigenetic domains across cancer types. Nature Genetics. 14:1345-51 Journal web link.
  15. Diep D, Zhang K. (2011) Genome-wide mapping of the sixth base. Genome Biology, 12:116 Journal web link
  16. Liu GH, Suzuki K, Qu J, Yi F, Li M, Sancho-Martinez I, Yi F, Li M, Kumar S, Nivet E, Kim J, Soligalla RD, Dubova I, Goebl A, Plongthongkum N, Fung HL, Zhang K, Loring JF, Laurent LC, Belmonte JC. (2011) Targeted gene correction of laminopathy-associated LMNA mutations in patient-specific iPSCs. Cell Stem Cell 8:688-94 Journal web link
  17. Xu Y, Wu F, Tan L, Kong L, Xiong L, Deng J, Barbera AJ, Zheng L, Zhang H, Huang S, Min J, Nicholson T, Chen T, Xu G, Shi Y, Zhang K, Shi YG. (2011). Genome-wide Regulation of 5hmC, 5mC, and Gene Expression by Tet1 Hydroxylase in Mouse Embryonic Stem Cells. Molecular cell. 42:451-64 Journal web link
  18. Howden SE, Gore A, Li Z, Fung HL, Nisler BS, Nie J, Chen G, McIntosh BE, Goulbranson DR, Diol NR, Taapken SM, Vereide DT, Montgomery KD, Zhang K, Gamm DM, Thomson JA. (2011) Genetic correction and analysis of induced pluripotent stem cells from a patient with gyrate atrophy.PNAS Journal web link
  19. Liu GH, Barkho BZ, Ruiz S, Diep D, Qu J, Yang SL, Panopoulos AD, Suzuki K, Kurian L, Walsh C, Thompson J, Boue S, Fung HL, Sancho-Martinez I, Zhang K, Iii JY, Belmonte JC. (2011). Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature [PMID: 21346760]
  20. Gore A*, Li Z*, Fung HL, Young JE, Agarwal S, Antosiewica-Gourget J, Canto I, Giorgetti A, Israel MA, Kiskinis E, Lee JK, Loh YH, Manos PD, Montserrat N, Panopoulos AD, Ruiz S, Wilbert ML, Yu J, Kirkness EF, Belmonte JCI, Rossi DJ, Thomson JA, Eggan K, Daley GQ, Goldstein LSB, Zhang K. (2011) Somatic coding mutations in human induced pluripotent stem cells. Nature 471:63-7
  21. Shoemaker R, Wang W, Zhang K (2010) Mediators and dynamics of DNA methylation. WIRES Biol Med. [PMID: 20878927]
  22. Shoemaker R, Deng J, Wang W, Zhang K. (2010) Allele-specific methylation is prevalent and is contributed by CpG-SNPs in the human genome. Genome Research 20:883-9
  23. Wang H, Chattopadhyay A, Li Z, Daines B, Li Y, Gao C., Gibbs R, Zhang K, Chen R. (2010). Rapid identification of heterozygous mutations in Drosophila melanogaster using genomic capture sequencing. Genome Research, 20: 981-988.
  24. Deng J, Shoemaker R, Xie B, Gore A, LeProust EM, Antosiewicz-Bourget J, Egli D, Maherali N, Park IH, Yu J, Daley GQ, Eggan K, Hochedlinger K, Thomson J, Wang W, Gao Y, Zhang K.(2009) Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming. Nature Biotechnology, 27:353-60 PDF
  25. Chen AE, Egli D, Niakan K, Deng J, Akutsu H, Yamaki M, Cowan C, Fitz-Gerald C, Zhang K, Melton DA, and Eggan K. (2009) Optimal timing of inner cell mass isolation increases the efficiency of human embryonic stem cell derivation and allows generation of sibling cell lines. Cell Stem Cell 4:103-6
  26. Lee JH, Park IH, Gao Y, Li JB, Li Z, Daley GQ, Zhang K*, Church GM*. (2009) A Robust Approach to Identifying Tissue-Specific Gene Expression Regulatory Variants Using Personalized Human Induced Pluripotent Stem Cells. PLoS Genetics, 5(11):e1000718.
  27. Zhang K, Li JB, Gao Y, Egli D, Xie B, Deng J, Li Z, Lee JH, Aach J, LeProust EM, Eggan K, Church GM (2009) Digital RNA allelotyping reveals tissue-specific and allele-specific gene expression in human. Nature Methods, 6:613-8
  28. Li JB*, Gao Y*, Aach J*, Zhang K*, Kryukov G, Xie B, Ahlford A, Yoon JK, Rosenbaum AM, Zaranek AW, LeProust E, Sunyaev S, Church GM. (2009) Multiplex padlock capture and sequencing reveal human hypermutable CpG variations. Genome Research, 19:1606-15.
  29. Li JB, Levanon EY, Yoon J-K, Aach J, Xie B, LeProust E, Zhang K, Gao Y, Church GM (2009) Genome-wide Identification of Human RNA Editing Sites by Massively Parallel DNA Capturing and Sequencing, Science 324:1210-13
  30. Porreca PJ*, Zhang K*, Li JB, Xie B, Austin D, Vassallo SL, LeProust EM, Peck BJ, Emig CJ, Dahl F, Gao Y, Church GM, Shendure J. (2007) Multiplex amplification of large sets of human exons. Nature Methods 4:931-6.
  31. Kowalchuk GA, Speksnijder AG, Zhang K, Goodman RM, van Veen JA. (2007) Finding the needles in the metagenome haystack. Microbial Ecology 53:475-85
  32. Zhang K, Lott ST, Jin L, Killary AM. (2007) Fine mapping of the NRC-1 tumor suppressor locus within chromosome 3p12. Biochemical and Biophysical Research Communications 360:531-538
  33. Zhang K, Martiny AC, Reppas NB, Barry KW, Malek J, Chisholm SW, Church GM. (2006) Sequencing genomes from single cells by polymerase cloning. Nature Biotechnology 24:680-686
  34. Zhang K, Zhu J, Shendure J, Porreca GJ, Aach JD, Mitra RD, Church GM. (2006) Polony haplotyping of individual human chromosome molecules. Nature Genetics 38:382-387.
  35. Shendure J, Porreca GJ, Reppas NB, Lin X, McCutcheon JP, Rosenbaum AM, Wang MD, Zhang K, Mitra RD, Church GM. (2005) Accurate multiplex polony sequencing of an evolved bacterial genome. Science 309:1728-1732.
  36. Zhang K, and Jin L. (2003) HaploBlockFinder: haplotype block analyses. Bioinformatics 19:1300-1301
  37. Zhang K, Akey JM (co-first author), Wang N, Xiong M, Chakraborty R, Jin L.(2003) Randomly distributed crossovers may generate block-like pattern of linkage disequibrium: An act of genetic drift. Human Genetics 113: 51-59.
  38. Akey JM, Zhang K, Xiong M, and Jin L. (2003) The effect of single nucleotide polymorphism identification strategies on estimates of linkage disequilibrium. Molecular Biology and Evolution 20: 232-242.
  39. Chen Z, Zhang K, Zhang X, Yuan XH, Yuan Z, Jin L, and Xiong M. (2003) Comparison of gene expression between metastatic derivatives and their poorly metastatic parental cells implicates crucial tumor-environment interaction in metastasis of head and neck squamous cell carcinoma. Clinical and Experimental Metastasis 20:335-342.
  40. Akey JM, Zhang G, Zhang K, Jin L and Shriver M. (2002) Interrogating a high-density SNP map for signatures of natural selection. Genome Research 12: 1805-1814.
  41. Wang N, Akey JM, Zhang K, Chakraborty R, Jin L. (2002) Distribution of recombination crossovers and the origin of haplotype blocks: the interplay of population history, recombination, and mutation. American Journal of Human Genetics 71: 1227-1234.
  42. Akey DT, Akey JM, Zhang K, Jin L. (2002) Assaying DNA methylation based on high-throughput melting curve approaches. Genomics 80: 376-384.
  43. Akey JM, Zhang K (co-first author), Xiong M, Doris P, Jin L. (2001) The effect that genotyping errors have on the robustness of common linkage-disequilibrium measures. American Journal of Human Genetics, 68:1447-1456.