Bio

Current Role at Stanford


My main work focuses on integrating proteomic mass spectrometry data with personalized human genomics to systematically study regulatory mechanisms of gene expression and the connections to human disease.

Education & Certifications


  • Ph.D., University of Connecticut, Biomedical Science (2007)
  • B.S., Fudan University, China, Biology (2002)

Publications

Journal Articles


  • Variation and genetic control of protein abundance in humans NATURE Wu, L., Candille, S. I., Choi, Y., Xie, D., Jiang, L., Li-Pook-Than, J., Tang, H., Snyder, M. 2013; 499 (7456): 79-82

    Abstract

    Gene expression differs among individuals and populations and is thought to be a major determinant of phenotypic variation. Although variation and genetic loci responsible for RNA expression levels have been analysed extensively in human populations, our knowledge is limited regarding the differences in human protein abundance and the genetic basis for this difference. Variation in messenger RNA expression is not a perfect surrogate for protein expression because the latter is influenced by an array of post-transcriptional regulatory mechanisms, and, empirically, the correlation between protein and mRNA levels is generally modest. Here we used isobaric tag-based quantitative mass spectrometry to determine relative protein levels of 5,953 genes in lymphoblastoid cell lines from 95 diverse individuals genotyped in the HapMap Project. We found that protein levels are heritable molecular phenotypes that exhibit considerable variation between individuals, populations and sexes. Levels of specific sets of proteins involved in the same biological process covary among individuals, indicating that these processes are tightly regulated at the protein level. We identified cis-pQTLs (protein quantitative trait loci), including variants not detected by previous transcriptome studies. This study demonstrates the feasibility of high-throughput human proteome quantification that, when integrated with DNA variation and transcriptome information, adds a new dimension to the characterization of gene expression regulation.

    View details for DOI 10.1038/nature12223

    View details for Web of Science ID 000321285600037

    View details for PubMedID 23676674

  • Dynamic Trans-Acting Factor Colocalization in Human Cells. Cell Xie*, D., Boyle*, A., Wu*, L., Zhai, J., Kawli, T., Snyder, M. 2013; 155 (3): 713–724
  • Defective sphingosine-1-phosphate receptor 1 (S1PR1) phosphorylation exacerbates Th17-mediated autoimmune neuroinflammation. Nature Immunology Garris*, C. S., Wu*, L., Acharya, S., et al 2013; 14 (11): 1166-72

    View details for DOI 10.1038/ni.2730.

  • Architecture of the human regulatory network derived from ENCODE data NATURE Gerstein, M. B., Kundaje, A., Hariharan, M., Landt, S. G., Yan, K., Cheng, C., Mu, X. J., Khurana, E., Rozowsky, J., Alexander, R., Min, R., Alves, P., Abyzov, A., Addleman, N., Bhardwaj, N., Boyle, A. P., Cayting, P., Charos, A., Chen, D. Z., Cheng, Y., Clarke, D., Eastman, C., Euskirchen, G., Frietze, S., Fu, Y., Gertz, J., Grubert, F., Harmanci, A., Jain, P., Kasowski, M., Lacroute, P., Leng, J., Lian, J., Monahan, H., O'Geen, H., Ouyang, Z., Partridge, E. C., Patacsil, D., Pauli, F., Raha, D., Ramirez, L., Reddy, T. E., Reed, B., Shi, M., Slifer, T., Wang, J., Wu, L., Yang, X., Yip, K. Y., Zilberman-Schapira, G., Batzoglou, S., Sidow, A., Farnham, P. J., Myers, R. M., Weissman, S. M., Snyder, M. 2012; 489 (7414): 91-100

    Abstract

    Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.

    View details for DOI 10.1038/nature11245

    View details for Web of Science ID 000308347000042

    View details for PubMedID 22955619

  • An integrated encyclopedia of DNA elements in the human genome NATURE Dunham, I., Kundaje, A., Aldred, S. F., Collins, P. J., Davis, C., Doyle, F., Epstein, C. B., Frietze, S., Harrow, J., Kaul, R., Khatun, J., Lajoie, B. R., Landt, S. G., Lee, B., Pauli, F., Rosenbloom, K. R., Sabo, P., Safi, A., Sanyal, A., Shoresh, N., Simon, J. M., Song, L., Trinklein, N. D., Altshuler, R. C., Birney, E., Brown, J. B., Cheng, C., Djebali, S., Dong, X., Dunham, I., Ernst, J., Furey, T. S., Gerstein, M., Giardine, B., Greven, M., Hardison, R. C., Harris, R. S., Herrero, J., Hoffman, M. M., Iyer, S., Kellis, M., Khatun, J., Kheradpour, P., Kundaje, A., Lassmann, T., Li, Q., Lin, X., Marinov, G. K., Merkel, A., Mortazavi, A., Parker, S. C., Reddy, T. E., Rozowsky, J., Schlesinger, F., Thurman, R. E., Wang, J., Ward, L. D., Whitfield, T. W., Wilder, S. P., Wu, W., Xi, H. S., Yip, K. Y., Zhuang, J., Bernstein, B. E., Birney, E., Dunham, I., Green, E. D., Gunter, C., Snyder, M., Pazin, M. J., Lowdon, R. F., Dillon, L. A., Adams, L. B., Kelly, C. J., Zhang, J., Wexler, J. R., Green, E. D., Good, P. J., Feingold, E. A., Bernstein, B. E., Birney, E., Crawford, G. E., Dekker, J., Elnitski, L., Farnham, P. J., Gerstein, M., Giddings, M. C., Gingeras, T. R., Green, E. D., Guigo, R., Hardison, R. C., Hubbard, T. J., Kellis, M., Kent, W. J., Lieb, J. D., Margulies, E. H., Myers, R. M., Snyder, M., Stamatoyannopoulos, J. A., Tenenbaum, S. A., Weng, Z., White, K. P., Wold, B., Khatun, J., Yu, Y., Wrobel, J., Risk, B. A., Gunawardena, H. P., Kuiper, H. C., Maier, C. W., Xie, L., Chen, X., Giddings, M. C., Bernstein, B. E., Epstein, C. B., Shoresh, N., Ernst, J., Kheradpour, P., Mikkelsen, T. S., Gillespie, S., Goren, A., Ram, O., Zhang, X., Wang, L., Issner, R., Coyne, M. J., Durham, T., Ku, M., Truong, T., Ward, L. D., Altshuler, R. C., Eaton, M. L., Kellis, M., Djebali, S., Davis, C. A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F., Xue, C., Marinov, G. K., Khatun, J., Williams, B. A., Zaleski, C., Rozowsky, J., Roeder, M., Kokocinski, F., Abdelhamid, R. F., Alioto, T., Antoshechkin, I., Baer, M. T., Batut, P., Bell, I., Bell, K., Chakrabortty, S., Chen, X., Chrast, J., Curado, J., Derrien, T., Drenkow, J., Dumais, E., Dumais, J., Duttagupta, R., Fastuca, M., Fejes-Toth, K., Ferreira, P., Foissac, S., Fullwood, M. J., Gao, H., Gonzalez, D., Gordon, A., Gunawardena, H. P., Howald, C., Jha, S., Johnson, R., Kapranov, P., King, B., Kingswood, C., Li, G., Luo, O. J., Park, E., Preall, J. B., Presaud, K., Ribeca, P., Risk, B. A., Robyr, D., Ruan, X., Sammeth, M., Sandhu, K. S., Schaeffer, L., See, L., Shahab, A., Skancke, J., Suzuki, A. M., Takahashi, H., Tilgner, H., Trout, D., Walters, N., Wang, H., Wrobel, J., Yu, Y., Hayashizaki, Y., Harrow, J., Gerstein, M., Hubbard, T. J., Reymond, A., Antonarakis, S. E., Hannon, G. J., Giddings, M. C., Ruan, Y., Wold, B., Carninci, P., Guigo, R., Gingeras, T. R., Rosenbloom, K. R., Sloan, C. A., Learned, K., Malladi, V. S., Wong, M. C., Barber, G., Cline, M. S., Dreszer, T. R., Heitner, S. G., Karolchik, D., Kent, W. J., Kirkup, V. M., Meyer, L. R., Long, J. C., Maddren, M., Raney, B. J., Furey, T. S., Song, L., Grasfeder, L. L., Giresi, P. G., Lee, B., Battenhouse, A., Sheffield, N. C., Simon, J. M., Showers, K. A., Safi, A., London, D., Bhinge, A. A., Shestak, C., Schaner, M. R., Kim, S. K., Zhang, Z. Z., Mieczkowski, P. A., Mieczkowska, J. O., Liu, Z., McDaniell, R. M., Ni, Y., Rashid, N. U., Kim, M. J., Adar, S., Zhang, Z., Wang, T., Winter, D., Keefe, D., Birney, E., Iyer, V. R., Lieb, J. D., Crawford, G. E., Li, G., Sandhu, K. S., Zheng, M., Wang, P., Luo, O. J., Shahab, A., Fullwood, M. J., Ruan, X., Ruan, Y., Myers, R. M., Pauli, F., Williams, B. A., Gertz, J., Marinov, G. K., Reddy, T. E., Vielmetter, J., Partridge, E. C., Trout, D., Varley, K. E., Gasper, C., Bansal, A., Pepke, S., Jain, P., Amrhein, H., Bowling, K. M., Anaya, M., Cross, M. K., King, B., Muratet, M. A., Antoshechkin, I., Newberry, K. M., McCue, K., Nesmith, A. S., Fisher-Aylor, K. I., Pusey, B., DeSalvo, G., Parker, S. L., Balasubramanian, S., Davis, N. S., Meadows, S. K., Eggleston, T., Gunter, C., Newberry, J. S., Levy, S. E., Absher, D. M., Mortazavi, A., Wong, W. H., Wold, B., Blow, M. J., Visel, A., Pennachio, L. A., Elnitski, L., Margulies, E. H., Parker, S. C., Petrykowska, H. M., Abyzov, A., Aken, B., Barrell, D., Barson, G., Berry, A., Bignell, A., Boychenko, V., Bussotti, G., Chrast, J., Davidson, C., Derrien, T., Despacio-Reyes, G., Diekhans, M., Ezkurdia, I., Frankish, A., Gilbert, J., Gonzalez, J. M., Griffiths, E., Harte, R., Hendrix, D. A., Howald, C., Hunt, T., Jungreis, I., Kay, M., Khurana, E., Kokocinski, F., Leng, J., Lin, M. F., Loveland, J., Lu, Z., Manthravadi, D., Mariotti, M., Mudge, J., Mukherjee, G., Notredame, C., Pei, B., Rodriguez, J. M., Saunders, G., Sboner, A., Searle, S., Sisu, C., Snow, C., Steward, C., Tanzer, A., Tapanari, E., Tress, M. L., van Baren, M. J., Walters, N., Washietl, S., Wilming, L., Zadissa, A., Zhang, Z., Brent, M., Haussler, D., Kellis, M., Valencia, A., Gerstein, M., Reymond, A., Guigo, R., Harrow, J., Hubbard, T. J., Landt, S. G., Frietze, S., Abyzov, A., Addleman, N., Alexander, R. P., Auerbach, R. K., Balasubramanian, S., Bettinger, K., Bhardwaj, N., Boyle, A. P., Cao, A. R., Cayting, P., Charos, A., Cheng, Y., Cheng, C., Eastman, C., Euskirchen, G., Fleming, J. D., Grubert, F., Habegger, L., Hariharan, M., Harmanci, A., Iyengar, S., Jin, V. X., Karczewski, K. J., Kasowski, M., Lacroute, P., Lam, H., Lamarre-Vincent, N., Leng, J., Lian, J., Lindahl-Allen, M., Min, R., Miotto, B., Monahan, H., Moqtaderi, Z., Mu, X. J., O'Geen, H., Ouyang, Z., Patacsil, D., Pei, B., Raha, D., Ramirez, L., Reed, B., Rozowsky, J., Sboner, A., Shi, M., Sisu, C., Slifer, T., Witt, H., Wu, L., Xu, X., Yan, K., Yang, X., Yip, K. Y., Zhang, Z., Struhl, K., Weissman, S. M., Gerstein, M., Farnham, P. J., Snyder, M., Tenenbaum, S. A., Penalva, L. O., Doyle, F., Karmakar, S., Landt, S. G., Bhanvadia, R. R., Choudhury, A., Domanus, M., Ma, L., Moran, J., Patacsil, D., Slifer, T., Victorsen, A., Yang, X., Snyder, M., White, K. P., Auer, T., Centanin, L., Eichenlaub, M., Gruhl, F., Heermann, S., Hoeckendorf, B., Inoue, D., Kellner, T., Kirchmaier, S., Mueller, C., Reinhardt, R., Schertel, L., Schneider, S., Sinn, R., Wittbrodt, B., Wittbrodt, J., Weng, Z., Whitfield, T. W., Wang, J., Collins, P. J., Aldred, S. F., Trinklein, N. D., Partridge, E. C., Myers, R. M., Dekker, J., Jain, G., Lajoie, B. R., Sanyal, A., Balasundaram, G., Bates, D. L., Byron, R., Canfield, T. K., Diegel, M. J., Dunn, D., Ebersol, A. K., Frum, T., Garg, K., Gist, E., Hansen, R. S., Boatman, L., Haugen, E., Humbert, R., Jain, G., Johnson, A. K., Johnson, E. M., Kutyavin, T. V., Lajoie, B. R., Lee, K., Lotakis, D., Maurano, M. T., Neph, S. J., Neri, F. V., Nguyen, E. D., Qu, H., Reynolds, A. P., Roach, V., Rynes, E., Sabo, P., Sanchez, M. E., Sandstrom, R. S., Sanyal, A., Shafer, A. O., Stergachis, A. B., Thomas, S., Thurman, R. E., Vernot, B., Vierstra, J., Vong, S., Wang, H., Weaver, M. A., Yan, Y., Zhang, M., Akey, J. M., Bender, M., Dorschner, M. O., Groudine, M., MacCoss, M. J., Navas, P., Stamatoyannopoulos, G., Kaul, R., Dekker, J., Stamatoyannopoulos, J. A., Dunham, I., Beal, K., Brazma, A., Flicek, P., Herrero, J., Johnson, N., Keefe, D., Lukk, M., Luscombe, N. M., Sobral, D., Vaquerizas, J. M., Wilder, S. P., Batzoglou, S., Sidow, A., Hussami, N., Kyriazopoulou-Panagiotopoulou, S., Libbrecht, M. W., Schaub, M. A., Kundaje, A., Hardison, R. C., Miller, W., Giardine, B., Harris, R. S., Wu, W., Bickel, P. J., Banfai, B., Boley, N. P., Brown, J. B., Huang, H., Li, Q., Li, J. J., Noble, W. S., Bilmes, J. A., Buske, O. J., Hoffman, M. M., Sahu, A. D., Kharchenko, P. V., Park, P. J., Baker, D., Taylor, J., Weng, Z., Iyer, S., Dong, X., Greven, M., Lin, X., Wang, J., Xi, H. S., Zhuang, J., Gerstein, M., Alexander, R. P., Balasubramanian, S., Cheng, C., Harmanci, A., Lochovsky, L., Min, R., Mu, X. J., Rozowsky, J., Yan, K., Yip, K. Y., Birney, E. 2012; 489 (7414): 57-74

    Abstract

    The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

    View details for DOI 10.1038/nature11247

    View details for Web of Science ID 000308347000039

    View details for PubMedID 22955616

  • A user's guide to the encyclopedia of DNA elements (ENCODE). PLoS biology 2011; 9 (4)

    Abstract

    The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome.

    View details for DOI 10.1371/journal.pbio.1001046

    View details for PubMedID 21526222

  • Close association of RNA polymerase II and many transcription factors with Pol III genes PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Raha, D., Wang, Z., Moqtaderi, Z., Wu, L., Zhong, G., Gerstein, M., Struhl, K., Snyder, M. 2010; 107 (8): 3639-3644

    Abstract

    Transcription of the eukaryotic genomes is carried out by three distinct RNA polymerases I, II, and III, whereby each polymerase is thought to independently transcribe a distinct set of genes. To investigate a possible relationship of RNA polymerases II and III, we mapped their in vivo binding sites throughout the human genome by using ChIP-Seq in two different cell lines, GM12878 and K562 cells. Pol III was found to bind near many known genes as well as several previously unidentified target genes. RNA-Seq studies indicate that a majority of the bound genes are expressed, although a subset are not suggestive of stalling by RNA polymerase III. Pol II was found to bind near many known Pol III genes, including tRNA, U6, HVG, hY, 7SK and previously unidentified Pol III target genes. Similarly, in vivo binding studies also reveal that a number of transcription factors normally associated with Pol II transcription, including c-Fos, c-Jun and c-Myc, also tightly associate with most Pol III-transcribed genes. Inhibition of Pol II activity using alpha-amanitin reduced expression of a number of Pol III genes (e.g., U6, hY, HVG), suggesting that Pol II plays an important role in regulating their transcription. These results indicate that, contrary to previous expectations, polymerases can often work with one another to globally coordinate gene expression.

    View details for DOI 10.1073/pnas.0911315106

    View details for Web of Science ID 000275130900066

    View details for PubMedID 20139302

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