Research statement:
My major fields of interest are computational biology and bioinformatics, coupled with the passion for the next-generation sequencing technologies, and a profound scientific interest in genomics, transcriptomics, regulation of gene expression, specificity of binding of transcription factors to the genome, histone modifications, nucleosome positioning, long-range genomic interactions and compartmentalization of the genome. My research lies on the frontier of the contemporary computational genomics, with the emphasis on development and testing of scripts and algorithms for the analysis of human genome and transcriptome. My focus is the improvement of methods for the various applications of the next generation sequencing, such as chromatin - immunoprecipitation sequencing or ChIP-Seq, RNA-sequencing or RNA-Seq, and probing open chromatin, DNase-Seq/ATAC-Seq, in order to answer key biological question that will ultimately help us understand better the underlying mechanisms of life. As a postdoc at Stanford?s Cardiovascular Institute, I am elucidating complex networks of interactions of transcription factors in human cardiac and vascular tissues, and molecular mechanisms that explain how cardiovascular disease risk-associated genomic loci confer disease risk. I am also employing allele specific computational pipelines to the existing next generation sequencing techniques, i.e. ChIP-Seq and RNA-Seq, in combination with the generation of eQTL data for human arterial smooth muscle cells (primary cell type of atherosclerotic lesions) to identify the causal variants that underlie disease susceptibility. In addition, I am modeling vascular SMC tissue-specific open chromatin with ATAC-Seq and DNase-Seq to understand the underlying mechanisms for cardiovascular disease causal variants. I am also active as a blogger, started a blog and continually post UNIX and R related tips and resolve computational problems that can be applied to genomics.

Professional Education

  • Master of Science, University of Belgrade (2005)
  • Doctor of Philosophy, Universite De Lausanne (2010)

Stanford Advisors


All Publications

  • Genetics and Genomics of Coronary Artery Disease. Current cardiology reports Pjanic, M., Miller, C. L., Wirka, R., Kim, J. B., Direnzo, D. M., Quertermous, T. 2016; 18 (10): 102-?


    Coronary artery disease (or coronary heart disease), is the leading cause of mortality in many of the developing as well as the developed countries of the world. Cholesterol-enriched plaques in the heart's blood vessels combined with inflammation lead to the lesion expansion, narrowing of blood vessels, reduced blood flow, and may subsequently cause lesion rupture and a heart attack. Even though several environmental risk factors have been established, such as high LDL-cholesterol, diabetes, and high blood pressure, the underlying genetic composition may substantially modify the disease risk; hence, genome composition and gene-environment interactions may be critical for disease progression. Ongoing scientific efforts have seen substantial advancements related to the fields of genetics and genomics, with the major breakthroughs yet to come. As genomics is the most rapidly advancing field in the life sciences, it is important to present a comprehensive overview of current efforts. Here, we present a summary of various genetic and genomics assays and approaches applied to coronary artery disease research.

    View details for DOI 10.1007/s11886-016-0777-y

    View details for PubMedID 27586139

  • Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci. Nature communications Miller, C. L., Pjanic, M., Wang, T., Nguyen, T., Cohain, A., Lee, J. D., Perisic, L., Hedin, U., Kundu, R. K., Majmudar, D., Kim, J. B., Wang, O., Betsholtz, C., Ruusalepp, A., Franzén, O., Assimes, T. L., Montgomery, S. B., Schadt, E. E., Björkegren, J. L., Quertermous, T. 2016; 7: 12092-?


    Coronary artery disease (CAD) is the leading cause of mortality and morbidity, driven by both genetic and environmental risk factors. Meta-analyses of genome-wide association studies have identified >150 loci associated with CAD and myocardial infarction susceptibility in humans. A majority of these variants reside in non-coding regions and are co-inherited with hundreds of candidate regulatory variants, presenting a challenge to elucidate their functions. Herein, we use integrative genomic, epigenomic and transcriptomic profiling of perturbed human coronary artery smooth muscle cells and tissues to begin to identify causal regulatory variation and mechanisms responsible for CAD associations. Using these genome-wide maps, we prioritize 64 candidate variants and perform allele-specific binding and expression analyses at seven top candidate loci: 9p21.3, SMAD3, PDGFD, IL6R, BMP1, CCDC97/TGFB1 and LMOD1. We validate our findings in expression quantitative trait loci cohorts, which together reveal new links between CAD associations and regulatory function in the appropriate disease context.

    View details for DOI 10.1038/ncomms12092

    View details for PubMedID 27386823

  • From Locus Association to Mechanism of Gene Causality: The Devil Is in the Details. Arteriosclerosis, thrombosis, and vascular biology Miller, C. L., Pjanic, M., Quertermous, T. 2015; 35 (10): 2079-2080

    View details for DOI 10.1161/ATVBAHA.115.306366

    View details for PubMedID 26399919

  • Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells that Contribute to the Fibrous Cap. Genomics data Nurnberg, S. T., Cheng, K., Raiesdana, A., Kundu, R., MILLER, C. L., Kim, J. B., Arora, K., Carcamo-Oribe, I., Xiong, Y., Tellakula, N., Nanda, V., Murthy, N., Boisvert, W. A., HEDIN, U., Perisic, L., Aldi, S., Maegdefessel, L., Pjanic, M., Owens, G. K., Tallquist, M. D., Quertermous, T. 2015; 5: 36-37


    TCF21 is a basic helix-loop-helix transcription factor that has recently been implicated as contributing to susceptibility to coronary heart disease based on genome wide association studies. In order to identify transcriptionally regulated target genes in a major disease relevant cell type, we performed siRNA knockdown of TCF21 in in vitro cultured human coronary artery smooth muscle cells and compared the transcriptome of siTCF21 versus siCONTROL treated cells. The raw (FASTQ) as well as processed (BED) data from 3 technical replicates per treatment has been deposited with Gene Expression Omnibus (GSE44461).

    View details for PubMedID 26090325

  • Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci. PLoS genetics Sazonova, O., Zhao, Y., Nürnberg, S., Miller, C., Pjanic, M., Castano, V. G., Kim, J. B., Salfati, E. L., Kundaje, A. B., Bejerano, G., Assimes, T., Yang, X., Quertermous, T. 2015; 11 (5)


    To functionally link coronary artery disease (CAD) causal genes identified by genome wide association studies (GWAS), and to investigate the cellular and molecular mechanisms of atherosclerosis, we have used chromatin immunoprecipitation sequencing (ChIP-Seq) with the CAD associated transcription factor TCF21 in human coronary artery smooth muscle cells (HCASMC). Analysis of identified TCF21 target genes for enrichment of molecular and cellular annotation terms identified processes relevant to CAD pathophysiology, including "growth factor binding," "matrix interaction," and "smooth muscle contraction." We characterized the canonical binding sequence for TCF21 as CAGCTG, identified AP-1 binding sites in TCF21 peaks, and by conducting ChIP-Seq for JUN and JUND in HCASMC confirmed that there is significant overlap between TCF21 and AP-1 binding loci in this cell type. Expression quantitative trait variation mapped to target genes of TCF21 was significantly enriched among variants with low P-values in the GWAS analyses, suggesting a possible functional interaction between TCF21 binding and causal variants in other CAD disease loci. Separate enrichment analyses found over-representation of TCF21 target genes among CAD associated genes, and linkage disequilibrium between TCF21 peak variation and that found in GWAS loci, consistent with the hypothesis that TCF21 may affect disease risk through interaction with other disease associated loci. Interestingly, enrichment for TCF21 target genes was also found among other genome wide association phenotypes, including height and inflammatory bowel disease, suggesting a functional profile important for basic cellular processes in non-vascular tissues. Thus, data and analyses presented here suggest that study of GWAS transcription factors may be a highly useful approach to identifying disease gene interactions and thus pathways that may be relevant to complex disease etiology.

    View details for DOI 10.1371/journal.pgen.1005202

    View details for PubMedID 26020271

  • Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap. PLoS genetics Nurnberg, S. T., Cheng, K., Raiesdana, A., Kundu, R., Miller, C. L., Kim, J. B., Arora, K., Carcamo-Oribe, I., Xiong, Y., Tellakula, N., Nanda, V., Murthy, N., Boisvert, W. A., Hedin, U., Perisic, L., Aldi, S., Maegdefessel, L., Pjanic, M., Owens, G. K., Tallquist, M. D., Quertermous, T. 2015; 11 (5)


    Recent genome wide association studies have identified a number of genes that contribute to the risk for coronary heart disease. One such gene, TCF21, encodes a basic-helix-loop-helix transcription factor believed to serve a critical role in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Using reporter gene and immunolocalization studies with mouse and human tissues we have found that vascular TCF21 expression in the adult is restricted primarily to adventitial cells associated with coronary arteries and also medial SMC in the proximal aorta of mouse. Genome wide RNA-Seq studies in human coronary artery SMC (HCASMC) with siRNA knockdown found a number of putative TCF21 downstream pathways identified by enrichment of terms related to CAD, including "vascular disease," "disorder of artery," and "occlusion of artery," as well as disease-related cellular functions including "cellular movement" and "cellular growth and proliferation." In vitro studies in HCASMC demonstrated that TCF21 expression promotes proliferation and migration and inhibits SMC lineage marker expression. Detailed in situ expression studies with reporter gene and lineage tracing revealed that vascular wall cells expressing Tcf21 before disease initiation migrate into vascular lesions of ApoE-/- and Ldlr-/- mice. While Tcf21 lineage traced cells are distributed throughout the early lesions, in mature lesions they contribute to the formation of a subcapsular layer of cells, and others become associated with the fibrous cap. The lineage traced fibrous cap cells activate expression of SMC markers and growth factor receptor genes. Taken together, these data suggest that TCF21 may have a role regulating the differentiation state of SMC precursor cells that migrate into vascular lesions and contribute to the fibrous cap and more broadly, in view of the association of this gene with human CAD, provide evidence that these processes may be a mechanism for CAD risk attributable to the vascular wall.

    View details for DOI 10.1371/journal.pgen.1005155

    View details for PubMedID 26020946

  • Molecular Characterization of a Human Matrix Attachment Region Epigenetic Regulator PLOS ONE Arope, S., Harraghy, N., Pjanic, M., Mermod, N. 2013; 8 (11)


    Matrix attachment regions (MAR) generally act as epigenetic regulatory sequences that increase gene expression, and they were proposed to partition chromosomes into loop-forming domains. However, their molecular mode of action remains poorly understood. Here, we assessed the possible contribution of the AT-rich core and adjacent transcription factor binding motifs to the transcription augmenting and anti-silencing effects of human MAR 1-68. Either flanking sequences together with the AT-rich core were required to obtain the full MAR effects. Shortened MAR derivatives retaining full MAR activity were constructed from combinations of the AT-rich sequence and multimerized transcription factor binding motifs, implying that both transcription factors and the AT-rich microsatellite sequence are required to mediate the MAR effect. Genomic analysis indicated that MAR AT-rich cores may be depleted of histones and enriched in RNA polymerase II, providing a molecular interpretation of their chromatin domain insulator and transcriptional augmentation activities.

    View details for DOI 10.1371/journal.pone.0079262

    View details for Web of Science ID 000327143800050

    View details for PubMedID 24244463

  • Nuclear Factor I genomic binding associates with chromatin boundaries BMC GENOMICS Pjanic, M., Schmid, C. D., Gaussin, A., Ambrosini, G., Adamcik, J., Pjanic, P., Plasari, G., Kerschgens, J., Dietler, G., Bucher, P., Mermod, N. 2013; 14


    The Nuclear Factor I (NFI) family of DNA binding proteins (also called CCAAT box transcription factors or CTF) is involved in both DNA replication and gene expression regulation. Using chromatin immuno-precipitation and high throughput sequencing (ChIP-Seq), we performed a genome-wide mapping of NFI DNA binding sites in primary mouse embryonic fibroblasts.We found that in vivo and in vitro NFI DNA binding specificities are indistinguishable, as in vivo ChIP-Seq NFI binding sites matched predictions based on previously established position weight matrix models of its in vitro binding specificity. Combining ChIP-Seq with mRNA profiling data, we found that NFI preferentially associates with highly expressed genes that it up-regulates, while binding sites were under-represented at expressed but unregulated genes. Genomic binding also correlated with markers of transcribed genes such as histone modifications H3K4me3 and H3K36me3, even outside of annotated transcribed loci, implying NFI in the control of the deposition of these modifications. Positional correlation between + and - strand ChIP-Seq tags revealed that, in contrast to other transcription factors, NFI associates with a nucleosomal length of cleavage-resistant DNA, suggesting an interaction with positioned nucleosomes. In addition, NFI binding prominently occurred at boundaries displaying discontinuities in histone modifications specific of expressed and silent chromatin, such as loci submitted to parental allele-specific imprinted expression.Our data thus suggest that NFI nucleosomal interaction may contribute to the partitioning of distinct chromatin domains and to epigenetic gene expression regulation.NFI ChIP-Seq and input control DNA data were deposited at Gene Expression Omnibus (GEO) repository under accession number GSE15844. Gene expression microarray data for mouse embryonic fibroblasts are on GEO accession number GSE15871.

    View details for DOI 10.1186/1471-2164-14-99

    View details for Web of Science ID 000316681000001

    View details for PubMedID 23402308

  • Nuclear factor I revealed as family of promoter binding transcription activators BMC GENOMICS Pjanic, M., Pjanic, P., Schmid, C., Ambrosini, G., Gaussin, A., Plasari, G., Mazza, C., Bucher, P., Mermod, N. 2011; 12


    Multiplex experimental assays coupled to computational predictions are being increasingly employed for the simultaneous analysis of many specimens at the genome scale, which quickly generates very large amounts of data. However, inferring valuable biological information from the comparisons of very large genomic datasets still represents an enormous challenge.As a study model, we chose the NFI/CTF family of mammalian transcription factors and we compared the results obtained from a genome-wide study of its binding sites with chromatin structure assays, gene expression microarray data, and in silico binding site predictions. We found that NFI/CTF family members preferentially bind their DNA target sites when they are located around transcription start sites when compared to control datasets generated from the random subsampling of the complete set of NFI binding sites. NFI proteins preferably associate with the upstream regions of genes that are highly expressed and that are enriched in active chromatin modifications such as H3K4me3 and H3K36me3. We postulate that this is a causal association and that NFI proteins mainly act as activators of transcription. This was documented for one member of the family (NFI-C), which revealed as a more potent gene activator than repressor in global gene expression analysis. Interestingly, we also discovered the association of NFI with the tri-methylation of lysine 9 of histone H3, a chromatin marker previously associated with the protection against silencing of telomeric genes by NFI.Taken together, we illustrate approaches that can be taken to analyze large genomic data, and provide evidence that NFI family members may act in conjunction with specific chromatin modifications to activate gene expression.

    View details for DOI 10.1186/1471-2164-12-181

    View details for Web of Science ID 000289898900001

    View details for PubMedID 21473784

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