Academic Appointments

Honors & Awards

  • NSF CAREER AWARD, National Science Foundation (2016-2021)
  • McCormick-Gabilan Fellowship, Stanford University (2015)
  • Alfred P. Sloan Research Fellow, Alfred P. Sloan Foundation (2014)
  • Baxter Faculty Scholar Award, Baxter Foundation (2014)
  • Pathway to Independence (K99/R00) Award, National Institutes of Health (2012-present)
  • Research Grant, National Science Foundation (2009-2012)
  • Magna Cum Laude, Princeton University (2002)

Professional Education

  • Ph. D., Stanford University, Statistics (2007)
  • A. B., Princeton University, Mathematics (2002)

Research & Scholarship

Current Research and Scholarly Interests

Circular RNA regulation and function; computational and experimental approaches


2019-20 Courses

Stanford Advisees

Graduate and Fellowship Programs


All Publications

  • Circular RNA biogenesis can proceed through an exon-containing lariat precursor. eLife Barrett, S. P., Wang, P. L., Salzman, J. 2015; 4


    Pervasive expression of circular RNA is a recently discovered feature of eukaryotic gene expression programs, yet its function remains largely unknown. The presumed biogenesis of these RNAs involves a non-canonical 'backsplicing' event. Recent studies in mammalian cell culture posit that backsplicing is facilitated by inverted repeats flanking the circularized exon(s). Although such sequence elements are common in mammals, they are rare in lower eukaryotes, making current models insufficient to describe circularization. Through systematic splice site mutagenesis and the identification of splicing intermediates, we show that circular RNA in Schizosaccharomyces pombe is generated through an exon-containing lariat precursor. Furthermore, we have performed high-throughput and comprehensive mutagenesis of a circle-forming exon, which enabled us to discover a systematic effect of exon length on RNA circularization. Our results uncover a mechanism for circular RNA biogenesis that may account for circularization in genes that lack noticeable flanking intronic secondary structure.

    View details for DOI 10.7554/eLife.07540

    View details for PubMedID 26057830

    View details for PubMedCentralID PMC4479058

  • Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development Genome biology Szabo1, L. 2015
  • Extensive site-directed mutagenesis reveals interconnected functional units in the alkaline phosphatase active site. eLife Sunden, F., Peck, A., Salzman, J., Ressl, S., Herschlag, D. 2015; 4


    Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called 'catalytic residues' are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modes of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes.

    View details for DOI 10.7554/eLife.06181

    View details for PubMedID 25902402

    View details for PubMedCentralID PMC4438272

  • Circular RNA Is Expressed across the Eukaryotic Tree of Life. PloS one Wang, P. L., Bao, Y., Yee, M., Barrett, S. P., Hogan, G. J., Olsen, M. N., Dinneny, J. R., Brown, P. O., Salzman, J. 2014; 9 (3)


    An unexpectedly large fraction of genes in metazoans (human, mouse, zebrafish, worm, fruit fly) express high levels of circularized RNAs containing canonical exons. Here we report that circular RNA isoforms are found in diverse species whose most recent common ancestor existed more than one billion years ago: fungi (Schizosaccharomyces pombe and Saccharomyces cerevisiae), a plant (Arabidopsis thaliana), and protists (Plasmodium falciparum and Dictyostelium discoideum). For all species studied to date, including those in this report, only a small fraction of the theoretically possible circular RNA isoforms from a given gene are actually observed. Unlike metazoans, Arabidopsis, D. discoideum, P. falciparum, S. cerevisiae, and S. pombe have very short introns (∼ 100 nucleotides or shorter), yet they still produce circular RNAs. A minority of genes in S. pombe and P. falciparum have documented examples of canonical alternative splicing, making it unlikely that all circular RNAs are by-products of alternative splicing or 'piggyback' on signals used in alternative RNA processing. In S. pombe, the relative abundance of circular to linear transcript isoforms changed in a gene-specific pattern during nitrogen starvation. Circular RNA may be an ancient, conserved feature of eukaryotic gene expression programs.

    View details for DOI 10.1371/journal.pone.0090859

    View details for PubMedID 24609083

    View details for PubMedCentralID PMC3946582

  • Best permutation analysis JOURNAL OF MULTIVARIATE ANALYSIS Rajaratnam, B., Salzman, J. 2013; 121: 193-223
  • Association between living environment and human oral viral ecology ISME JOURNAL Robles-Sikisaka, R., Ly, M., Boehm, T., Naidu, M., Salzman, J., Pride, D. T. 2013; 7 (9): 1710-1724


    The human oral cavity has an indigenous microbiota known to include a robust community of viruses. Very little is known about how oral viruses are spread throughout the environment or to which viruses individuals are exposed. We sought to determine whether shared living environment is associated with the composition of human oral viral communities by examining the saliva of 21 human subjects; 11 subjects from different households and 10 unrelated subjects comprising 4 separate households. Although there were many viral homologues shared among all subjects studied, there were significant patterns of shared homologues in three of the four households that suggest shared living environment affects viral community composition. We also examined CRISPR (clustered regularly interspaced short palindromic repeat) loci, which are involved in acquired bacterial and archaeal resistance against invading viruses by acquiring short viral sequences. We analyzed 2 065 246 CRISPR spacers from 5 separate repeat motifs found in oral bacterial species of Gemella, Veillonella, Leptotrichia and Streptococcus to determine whether individuals from shared living environments may have been exposed to similar viruses. A significant proportion of CRISPR spacers were shared within subjects from the same households, suggesting either shared ancestry of their oral microbiota or similar viral exposures. Many CRISPR spacers matched virome sequences from different subjects, but no pattern specific to any household was found. Our data on viromes and CRISPR content indicate that shared living environment may have a significant role in determining the ecology of human oral viruses.

    View details for DOI 10.1038/ismej.2013.63

    View details for Web of Science ID 000323385600004

    View details for PubMedID 23598790

  • Cell-type specific features of circular RNA expression. PLoS genetics Salzman, J., Chen, R. E., Olsen, M. N., Wang, P. L., Brown, P. O. 2013; 9 (9)


    Thousands of loci in the human and mouse genomes give rise to circular RNA transcripts; at many of these loci, the predominant RNA isoform is a circle. Using an improved computational approach for circular RNA identification, we found widespread circular RNA expression in Drosophila melanogaster and estimate that in humans, circular RNA may account for 1% as many molecules as poly(A) RNA. Analysis of data from the ENCODE consortium revealed that the repertoire of genes expressing circular RNA, the ratio of circular to linear transcripts for each gene, and even the pattern of splice isoforms of circular RNAs from each gene were cell-type specific. These results suggest that biogenesis of circular RNA is an integral, conserved, and regulated feature of the gene expression program.

    View details for DOI 10.1371/journal.pgen.1003777

    View details for PubMedID 24039610

    View details for PubMedCentralID PMC3764148

  • A penalized likelihood approach for robust estimation of isoform expression eprint arXiv:1310.0379 Jiang, H., Salzman, . 2013
  • Improved discovery of molecular interactions in genome-scale data with adaptive model-based normalization. PloS one Salzman, J., Klass, D. M., Brown, P. O. 2013; 8 (1)


    High throughput molecular-interaction studies using immunoprecipitations (IP) or affinity purifications are powerful and widely used in biology research. One of many important applications of this method is to identify the set of RNAs that interact with a particular RNA-binding protein (RBP). Here, the unique statistical challenge presented is to delineate a specific set of RNAs that are enriched in one sample relative to another, typically a specific IP compared to a non-specific control to model background. The choice of normalization procedure critically impacts the number of RNAs that will be identified as interacting with an RBP at a given significance threshold - yet existing normalization methods make assumptions that are often fundamentally inaccurate when applied to IP enrichment data.In this paper, we present a new normalization methodology that is specifically designed for identifying enriched RNA or DNA sequences in an IP. The normalization (called adaptive or AD normalization) uses a basic model of the IP experiment and is not a variant of mean, quantile, or other methodology previously proposed. The approach is evaluated statistically and tested with simulated and empirical data.The adaptive (AD) normalization method results in a greatly increased range in the number of enriched RNAs identified, fewer false positives, and overall better concordance with independent biological evidence, for the RBPs we analyzed, compared to median normalization. The approach is also applicable to the study of pairwise RNA, DNA and protein interactions such as the analysis of transcription factors via chromatin immunoprecipitation (ChIP) or any other experiments where samples from two conditions, one of which contains an enriched subset of the other, are studied.

    View details for DOI 10.1371/journal.pone.0053930

    View details for PubMedID 23349766

    View details for PubMedCentralID PMC3551948

  • Statistical properties of an early stopping rule for resampling-based multiple testing BIOMETRIKA Jiang, H., Salzman, J. 2012; 99 (4): 973-980
  • Extensive Gene-Specific Translational Reprogramming in a Model of B Cell Differentiation and Abl-Dependent Transformation PLOS ONE Bates, J. G., Salzman, J., May, D., Garcia, P. B., Hogan, G. J., McIntosh, M., Schlissel, M. S., Brown, P. O. 2012; 7 (5)


    To what extent might the regulation of translation contribute to differentiation programs, or to the molecular pathogenesis of cancer? Pre-B cells transformed with the viral oncogene v-Abl are suspended in an immortalized, cycling state that mimics leukemias with a BCR-ABL1 translocation, such as Chronic Myelogenous Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL). Inhibition of the oncogenic Abl kinase with imatinib reverses transformation, allowing progression to the next stage of B cell development. We employed a genome-wide polysome profiling assay called Gradient Encoding to investigate the extent and potential contribution of translational regulation to transformation and differentiation in v-Abl-transformed pre-B cells. Over half of the significantly translationally regulated genes did not change significantly at the level of mRNA abundance, revealing biology that might have been missed by measuring changes in transcript abundance alone. We found extensive, gene-specific changes in translation affecting genes with known roles in B cell signaling and differentiation, cancerous transformation, and cytoskeletal reorganization potentially affecting adhesion. These results highlight a major role for gene-specific translational regulation in remodeling the gene expression program in differentiation and malignant transformation.

    View details for DOI 10.1371/journal.pone.0037108

    View details for Web of Science ID 000305338500030

    View details for PubMedID 22693568

  • Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome ISME JOURNAL Pride, D. T., Salzman, J., Haynes, M., Rohwer, F., Davis-Long, C., White, R. A., Loomer, P., Armitage, G. C., Relman, D. A. 2012; 6 (5): 915-926


    Viruses are the most abundant known infectious agents on the planet and are significant drivers of diversity in a variety of ecosystems. Although there have been numerous studies of viral communities, few have focused on viruses within the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral particles and compared them with 263 516 bacterial 16S rRNA gene sequences from the saliva of five healthy human subjects over a 2- to 3-month period, in order to improve our understanding of the role viruses have in the complex oral ecosystem. Our data reveal viral communities in human saliva dominated by bacteriophages whose constituents are temporally distinct. The preponderance of shared homologs between the salivary viral communities in two unrelated subjects in the same household suggests that environmental factors are determinants of community membership. When comparing salivary viromes to those from human stool and the respiratory tract, each group was distinct, further indicating that habitat is of substantial importance in shaping human viromes. Compared with coexisting bacteria, there was concordance among certain predicted host-virus pairings such as Veillonella and Streptococcus, whereas there was discordance among others such as Actinomyces. We identified 122 728 virulence factor homologs, suggesting that salivary viruses may serve as reservoirs for pathogenic gene function in the oral environment. That the vast majority of human oral viruses are bacteriophages whose putative gene function signifies some have a prominent role in lysogeny, suggests these viruses may have an important role in helping shape the microbial diversity in the human oral cavity.

    View details for DOI 10.1038/ismej.2011.169

    View details for Web of Science ID 000302950700002

    View details for PubMedID 22158393

    View details for PubMedCentralID PMC3329113

  • Widespread mRNA Association with Cytoskeletal Motor Proteins and Identification and Dynamics of Myosin-Associated mRNAs in S. cerevisiae PLOS ONE Casolari, J. M., Thompson, M. A., Salzman, J., Champion, L. M., Moerner, W. E., Brown, P. O. 2012; 7 (2)


    Programmed mRNA localization to specific subcellular compartments for localized translation is a fundamental mechanism of post-transcriptional regulation that affects many, and possibly all, mRNAs in eukaryotes. We describe here a systematic approach to identify the RNA cargoes associated with the cytoskeletal motor proteins of Saccharomyces cerevisiae in combination with live-cell 3D super-localization microscopy of endogenously tagged mRNAs. Our analysis identified widespread association of mRNAs with cytoskeletal motor proteins, including association of Myo3 with mRNAs encoding key regulators of actin branching and endocytosis such as WASP and WIP. Using conventional fluorescence microscopy and expression of MS2-tagged mRNAs from endogenous loci, we observed a strong bias for actin patch nucleator mRNAs to localize to the cell cortex and the actin patch in a Myo3- and F-actin dependent manner. Use of a double-helix point spread function (DH-PSF) microscope allowed super-localization measurements of single mRNPs at a spatial precision of 25 nm in x and y and 50 nm in z in live cells with 50 ms exposure times, allowing quantitative profiling of mRNP dynamics. The actin patch mRNA exhibited distinct and characteristic diffusion coefficients when compared to a control mRNA. In addition, disruption of F-actin significantly expanded the 3D confinement radius of an actin patch nucleator mRNA, providing a quantitative assessment of the contribution of the actin cytoskeleton to mRNP dynamic localization. Our results provide evidence for specific association of mRNAs with cytoskeletal motor proteins in yeast, suggest that different mRNPs have distinct and characteristic dynamics, and lend insight into the mechanism of actin patch nucleator mRNA localization to actin patches.

    View details for DOI 10.1371/journal.pone.0031912

    View details for Web of Science ID 000302796200110

    View details for PubMedID 22359641

    View details for PubMedCentralID PMC3281097

  • Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types PLOS ONE Salzman, J., Gawad, C., Wang, P. L., Lacayo, N., Brown, P. O. 2012; 7 (2)


    Most human pre-mRNAs are spliced into linear molecules that retain the exon order defined by the genomic sequence. By deep sequencing of RNA from a variety of normal and malignant human cells, we found RNA transcripts from many human genes in which the exons were arranged in a non-canonical order. Statistical estimates and biochemical assays provided strong evidence that a substantial fraction of the spliced transcripts from hundreds of genes are circular RNAs. Our results suggest that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a general feature of the gene expression program in human cells.

    View details for DOI 10.1371/journal.pone.0030733

    View details for Web of Science ID 000301977500016

    View details for PubMedID 22319583

    View details for PubMedCentralID PMC3270023

  • Comparisons of CRISPRs and viromes in human saliva reveal bacterial 3 adaptations to salivary viruses Environmental Microbiology Pride, D. 2012
  • ESRRA-C11orf20 Is a Recurrent Gene Fusion in Serous Ovarian Carcinoma PLOS BIOLOGY Salzman, J., Marinelli, R. J., Wang, P. L., Green, A. E., Nielsen, J. S., Nelson, B. H., Drescher, C. W., Brown, P. O. 2011; 9 (9)


    Every year, ovarian cancer kills approximately 14,000 women in the United States and more than 140,000 women worldwide. Most of these deaths are caused by tumors of the serous histological type, which is rarely diagnosed before it has disseminated. By deep paired-end sequencing of mRNA from serous ovarian cancers, followed by deep sequencing of the corresponding genomic region, we identified a recurrent fusion transcript. The fusion transcript joins the 5' exons of ESRRA, encoding a ligand-independent member of the nuclear-hormone receptor superfamily, to the 3' exons of C11orf20, a conserved but uncharacterized gene located immediately upstream of ESRRA in the reference genome. To estimate the prevalence of the fusion, we tested 67 cases of serous ovarian cancer by RT-PCR and sequencing and confirmed its presence in 10 of these. Targeted resequencing of the corresponding genomic region from two fusion-positive tumor samples identified a nearly clonal chromosomal rearrangement positioning ESRRA upstream of C11orf20 in one tumor, and evidence of local copy number variation in the ESRRA locus in the second tumor. We hypothesize that the recurrent novel fusion transcript may play a role in pathogenesis of a substantial fraction of serous ovarian cancers and could provide a molecular marker for detection of the cancer. Gene fusions involving adjacent or nearby genes can readily escape detection but may play important roles in the development and progression of cancer.

    View details for DOI 10.1371/journal.pbio.1001156

    View details for Web of Science ID 000295372800012

    View details for PubMedID 21949640

    View details for PubMedCentralID PMC3176749

  • Statistical Modeling of RNA-Seq Data STATISTICAL SCIENCE Salzman, J., Jiang, H., Wong, W. H. 2011; 26 (1): 62-83

    View details for DOI 10.1214/10-STS343

    View details for Web of Science ID 000292424900013

  • Analysis of streptococcal CRISPRs from human saliva reveals substantial sequence diversity within and between subjects over time GENOME RESEARCH Pride, D. T., Sun, C. L., Salzman, J., Rao, N., Loomer, P., Armitage, G. C., Banfield, J. F., Relman, D. A. 2011; 21 (1): 126-136


    Viruses may play an important role in the evolution of human microbial communities. Clustered regularly interspaced short palindromic repeats (CRISPRs) provide bacteria and archaea with adaptive immunity to previously encountered viruses. Little is known about CRISPR composition in members of human microbial communities, the relative rate of CRISPR locus change, or how CRISPR loci differ between the microbiota of different individuals. We collected saliva from four periodontally healthy human subjects over an 11- to 17-mo time period and analyzed CRISPR sequences with corresponding streptococcal repeats in order to improve our understanding of the predominant features of oral streptococcal adaptive immune repertoires. We analyzed a total of 6859 CRISPR bearing reads and 427,917 bacterial 16S rRNA gene sequences. We found a core (ranging from 7% to 22%) of shared CRISPR spacers that remained stable over time within each subject, but nearly a third of CRISPR spacers varied between time points. We document high spacer diversity within each subject, suggesting constant addition of new CRISPR spacers. No greater than 2% of CRISPR spacers were shared between subjects, suggesting that each individual was exposed to different virus populations. We detect changes in CRISPR spacer sequence diversity over time that may be attributable to locus diversification or to changes in streptococcal population structure, yet the composition of the populations within subjects remained relatively stable. The individual-specific and traceable character of CRISPR spacer complements could potentially open the way for expansion of the domain of personalized medicine to the oral microbiome, where lineages may be tracked as a function of health and other factors.

    View details for DOI 10.1101/gr.111732.110

    View details for Web of Science ID 000285868300013

    View details for PubMedID 21149389

    View details for PubMedCentralID PMC3012920

  • Proteome-Wide Search Reveals Unexpected RNA-Binding Proteins in Saccharomyces cerevisiae PLOS ONE Tsvetanova, N. G., Klass, D. M., Salzman, J., Brown, P. O. 2010; 5 (9)


    The vast landscape of RNA-protein interactions at the heart of post-transcriptional regulation remains largely unexplored. Indeed it is likely that, even in yeast, a substantial fraction of the regulatory RNA-binding proteins (RBPs) remain to be discovered. Systematic experimental methods can play a key role in discovering these RBPs--most of the known yeast RBPs lack RNA-binding domains that might enable this activity to be predicted. We describe here a proteome-wide approach to identify RNA-protein interactions based on in vitro binding of RNA samples to yeast protein microarrays that represent over 80% of the yeast proteome. We used this procedure to screen for novel RBPs and RNA-protein interactions. A complementary mass spectrometry technique also identified proteins that associate with yeast mRNAs. Both the protein microarray and mass spectrometry methods successfully identify previously annotated RBPs, suggesting that other proteins identified in these assays might be novel RBPs. Of 35 putative novel RBPs identified by either or both of these methods, 12, including 75% of the eight most highly-ranked candidates, reproducibly associated with specific cellular RNAs. Surprisingly, most of the 12 newly discovered RBPs were enzymes. Functional characteristics of the RNA targets of some of the novel RBPs suggest coordinated post-transcriptional regulation of subunits of protein complexes and a possible link between mRNA trafficking and vesicle transport. Our results suggest that many more RBPs still remain to be identified and provide a set of candidates for further investigation.

    View details for DOI 10.1371/journal.pone.0012671

    View details for Web of Science ID 000281687300015

    View details for PubMedID 20844764

    View details for PubMedCentralID PMC2937035

  • Reliable concurrent calling of multiple genetic alleles and 24-chromosome ploidy without embryo freezing using parental support™ technology (PS) Fertility and Sterility Rabinowitz, M. 2008
  • Limits on the ability of quantum states to convey classical messages JOURNAL OF THE ACM Nayak, A., Salzman, J. 2006; 53 (1): 184-206
  • An improved upper bound for the pebbling threshold of the n-path Discrete Mathematics Wierman, A. 2004