Honors & Awards

  • Merit Student, Graduate University of Chinese Academy of Sciences (2013)
  • Excellent Graduate, Graduate University of Chinese Academy of Sciences (2014)

Professional Education

  • Doctor of Philosophy, Chinese Academy Of Sciences (2014)
  • Bachelor of Engineering, Northeast Normal University (2007)

Stanford Advisors

Research & Scholarship

Current Research and Scholarly Interests

I am interested in the biological process of RNA transcript and translation regulation, specifically by the regulation of no-coding RNA, stochastic gene expression and RNA structures.

Lab Affiliations


All Publications

  • Landscape of monoallelic DNA accessibility in mouse embryonic stem cells and neural progenitor cells. Nature genetics Xu, J., Carter, A. C., Gendrel, A., Attia, M., Loftus, J., Greenleaf, W. J., Tibshirani, R., Heard, E., Chang, H. Y. 2017; 49 (3): 377-386


    We developed an allele-specific assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) to genotype and profile active regulatory DNA across the genome. Using a mouse hybrid F1 system, we found that monoallelic DNA accessibility across autosomes was pervasive, developmentally programmed and composed of several patterns. Genetically determined accessibility was enriched at distal enhancers, but random monoallelically accessible (RAMA) elements were enriched at promoters and may act as gatekeepers of monoallelic mRNA expression. Allelic choice at RAMA elements was stable across cell generations and bookmarked through mitosis. RAMA elements in neural progenitor cells were biallelically accessible in embryonic stem cells but premarked with bivalent histone modifications; one allele was silenced during differentiation. Quantitative analysis indicated that allelic choice at the majority of RAMA elements is consistent with a stochastic process; however, up to 30% of RAMA elements may deviate from the expected pattern, suggesting a regulated or counting mechanism.

    View details for DOI 10.1038/ng.3769

    View details for PubMedID 28112738

    View details for PubMedCentralID PMC5357084

  • Novel Gene Expression Profile of Women with Intrinsic Skin Youthfulness by Whole Transcriptome Sequencing PLOS ONE Xu, J., Spitale, R. C., Guan, L., Flynn, R. A., Torre, E. A., Li, R., Reber, I., Qu, K., Kern, D., Knaggs, H. E., Chang, H. Y., Chang, A. L. 2016; 11 (11)
  • Molecular and Neural Functions of Rai1, the Causal Gene for Smith-Magenis Syndrome. Neuron Huang, W., Guenthner, C. J., Xu, J., Nguyen, T., Schwarz, L. A., Wilkinson, A. W., Gozani, O., Chang, H. Y., Shamloo, M., Luo, L. 2016; 92 (2): 392-406


    Haploinsufficiency of Retinoic Acid Induced 1 (RAI1) causes Smith-Magenis syndrome (SMS), which is associated with diverse neurodevelopmental and behavioral symptoms as well as obesity. RAI1 encodes a nuclear protein but little is known about its molecular function or the cell types responsible for SMS symptoms. Using genetically engineered mice, we found that Rai1 preferentially occupies DNA regions near active promoters and promotes the expression of a group of genes involved in circuit assembly and neuronal communication. Behavioral analyses demonstrated that pan-neural loss of Rai1 causes deficits in motor function, learning, and food intake. These SMS-like phenotypes are produced by loss of Rai1 function in distinct neuronal types: Rai1 loss in inhibitory neurons or subcortical glutamatergic neurons causes learning deficits, while Rai1 loss in Sim1(+) or SF1(+) cells causes obesity. By integrating molecular and organismal analyses, our study suggests potential therapeutic avenues for a complex neurodevelopmental disorder.

    View details for DOI 10.1016/j.neuron.2016.09.019

    View details for PubMedID 27693255

  • Structural organization of the inactive X chromosome in the mouse NATURE Giorgetti, L., Lajoie, B. R., Carter, A. C., Attia, M., Zhan, Y., Xu, J., Chen, C. J., Kaplan, N., Chang, H. Y., Heard, E., Dekker, J. 2016; 535 (7613): 575-?


    X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed. Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite. However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions,remains unclear. Here we investigate the structure, chromatin accessibility and expression status of the mouse Xi chromosome in highly polymorphic clonal neural progenitors (NPCs) and embryonic stem cells. We demonstrate a crucial role for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and RNA sequencing. Deletion of the boundary disrupts mega-domain formation, and induction of Xist RNA initiates formation of the boundary and the loss of DNA accessibility. We also show that in NPCs, the Xi chromosome lacks active/inactive compartments and topologically associating domains (TADs), except around genes that escape XCI. Escapee gene clusters display TAD-like structures and retain DNA accessibility at promoter-proximal and CTCF-binding sites. Furthermore, altered patterns of facultative escape genes indifferent neural progenitor clones are associated with the presence of different TAD-like structures after XCI. These findings suggest a key role for transcription and CTCF in the formation of TADs in the context of the Xi chromosome in neural progenitors.

    View details for DOI 10.1038/nature18589

    View details for Web of Science ID 000380856600034

    View details for PubMedID 27437574

    View details for PubMedCentralID PMC5443622

  • Assessment of the Genetic Basis of Rosacea by Genome-Wide Association Study JOURNAL OF INVESTIGATIVE DERMATOLOGY Chang, A. L., Raber, I., Xu, J., Li, R., Spitale, R., Chen, J., Kiefer, A. K., Tian, C., Eriksson, N. K., Hinds, D. A., Tung, J. Y. 2015; 135 (6): 1548-1555


    Rosacea is a common, chronic skin disease that is currently incurable. Although environmental factors influence rosacea, the genetic basis of rosacea is not established. In this genome-wide association study, a discovery group of 22,952 individuals (2,618 rosacea cases and 20,334 controls) was analyzed, leading to identification of two significant single-nucleotide polymorphisms (SNPs) associated with rosacea, one of which replicated in a new group of 29,481 individuals (3,205 rosacea cases and 26,262 controls). The confirmed SNP, rs763035 (P=8.0 × 10(-11) discovery group; P=0.00031 replication group), is intergenic between HLA-DRA and BTNL2. Exploratory immunohistochemical analysis of HLA-DRA and BTNL2 expression in papulopustular rosacea lesions from six individuals, including one with the rs763035 variant, revealed staining in the perifollicular inflammatory infiltrate of rosacea for both proteins. In addition, three HLA alleles, all MHC class II proteins, were significantly associated with rosacea in the discovery group and confirmed in the replication group: HLA-DRB1*03:01 (P=1.0 × 10(-8) discovery group; P=4.4 × 10(-6) replication group), HLA-DQB1*02:01 (P=1.3 × 10(-8) discovery group; P=7.2 × 10(-6) replication group), and HLA-DQA1*05:01 (P=1.4 × 10(-8) discovery group; P=7.6 × 10(-6) replication group). Collectively, the gene variants identified in this study support the concept of a genetic component for rosacea, and provide candidate targets for future studies to better understand and treat rosacea.

    View details for DOI 10.1038/jid.2015.53

    View details for Web of Science ID 000354389200015

    View details for PubMedID 25695682

    View details for PubMedCentralID PMC4434179

  • The evolution of evolvability in microRNA target sites in vertebrates GENOME RESEARCH Xu, J., Zhang, R., Shen, Y., Liu, G., Lu, X., Wu, C. 2013; 23 (11): 1810-1816


    The lack of long-term evolutionary conservation of microRNA (miRNA) target sites appears to contradict many analyses of their functions. Several hypotheses have been offered, but an attractive one-that the conservation may be a function of taxonomic hierarchy (vertebrates, mammals, primates, etc.)-has rarely been discussed. For such an analysis, we cannot use evolutionary conservation as a criterion of target identification, and hence, have used high confidence target sites in the cross-linking immunoprecipitation (CLIP) data. Assuming that a proportion, p, of target sites in the CLIP data are conserved, we define the evolvability of miRNA targets as 1-p. Genomic data from vertebrate species show that the evolvability between human and fish is very high, at more than 90%. The evolvability decreases to 50% between birds and mammals, 20% among mammalian orders, and only 6% between human and chimpanzee. Within each taxonomic hierarchy, there is a set of targets that are conserved only at that level of evolution. Extrapolating the evolutionary trend, we find the evolvability in any single species to be close to 0%. Thus, all miRNA target sites identified by the CLIP method are evolutionarily conserved in one species, but the conservation is lost step by step in larger taxonomic groups. The changing evolvability of miRNA targets suggests that miRNA-target interactions may play a role in the evolution of organismal diversity.

    View details for DOI 10.1101/gr.148916.112

    View details for Web of Science ID 000326642500005

    View details for PubMedID 24077390

  • Rapid growth of a hepatocellular carcinoma and the driving mutations revealed by cell-population genetic analysis of whole-genome data PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Tao, Y., Ruan, J., Yeh, S., Lu, X., Wang, Y., Zhai, W., Cai, J., Ling, S., Gong, Q., Chong, Z., Qu, Z., Li, Q., Liu, J., Yang, J., Zheng, C., Zeng, C., Wang, H., Zhang, J., Wang, S., Hao, L., Dong, L., Li, W., Sun, M., Zou, W., Yu, C., Li, C., Liu, G., Jiang, L., Xu, J., Huang, H., Li, C., Mi, S., Zhang, B., Chen, B., Zhao, W., Hu, S., Zhuang, S., Shen, Y., Shi, S., Brown, C., White, K. P., Chen, D., Chen, P., Wu, C. 2011; 108 (29): 12042-12047


    We present the analysis of the evolution of tumors in a case of hepatocellular carcinoma. This case is particularly informative about cancer growth dynamics and the underlying driving mutations. We sampled nine different sections from three tumors and seven more sections from the adjacent nontumor tissues. Selected sections were subjected to exon as well as whole-genome sequencing. Putative somatic mutations were then individually validated across all 9 tumor and 7 nontumor sections. Among the mutations validated, 24 were amino acid changes; in addition, 22 large indels/copy number variants (>1 Mb) were detected. These somatic mutations define four evolutionary lineages among tumor cells. Separate evolution and expansion of these lineages were recent and rapid, each apparently having only one lineage-specific protein-coding mutation. Hence, by using a cell-population genetic definition, this approach identified three coding changes (CCNG1, P62, and an indel/fusion gene) as tumor driver mutations. These three mutations, affecting cell cycle control and apoptosis, are functionally distinct from mutations that accumulated earlier, many of which are involved in inflammation/immunity or cell anchoring. These distinct functions of mutations at different stages may reflect the genetic interactions underlying tumor growth.

    View details for DOI 10.1073/pnas.1108715108

    View details for Web of Science ID 000292876900066

    View details for PubMedID 21730188

  • Genome-wide misexpression of X-linked versus autosomal genes associated with hybrid male sterility GENOME RESEARCH Lu, X., Shapiro, J. A., Ting, C., Li, Y., Li, C., Xu, J., Huang, H., Cheng, Y., Greenberg, A. J., Li, S., Wu, M., Shen, Y., Wu, C. 2010; 20 (8): 1097-1102


    Postmating reproductive isolation is often manifested as hybrid male sterility, for which X-linked genes are overrepresented (the so-called large X effect). In contrast, X-linked genes are significantly under-represented among testis-expressing genes. This seeming contradiction may be germane to the X:autosome imbalance hypothesis on hybrid sterility, in which the X-linked effect is mediated mainly through the misexpression of autosomal genes. In this study, we compared gene expression in fertile and sterile males in the hybrids between two Drosophila species. These hybrid males differ only in a small region of the X chromosome containing the Ods-site homeobox (OdsH) (also known as Odysseus) locus of hybrid sterility. Of genes expressed in the testis, autosomal genes were, indeed, more likely to be misexpressed than X-linked genes under the sterilizing action of OdsH. Since this mechanism of X:autosome interaction is only associated with spermatogenesis, a connection between X:autosome imbalance and the high rate of hybrid male sterility seems plausible.

    View details for DOI 10.1101/gr.076620.108

    View details for Web of Science ID 000280709800008

    View details for PubMedID 20511493

  • The O-acylation of ketone enolates by allyl 1H-imidazole-1-carboxylate mediated with boron trifluoride etherate - A convenient procedure for the synthesis of substituted allyl enol carbonates JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Xu, J. 2007; 72 (24): 9372-9375


    A convenient access to substituted allyl enol carbonates was established through the reaction of ketone enolates with the complex of allyl 1H-imidazole-1-carboxylates and boron trifluoride etherate.

    View details for DOI 10.1021/jo7016313

    View details for Web of Science ID 000251039700052

    View details for PubMedID 17963405

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