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Senior Investigator

Translational and Functional Genomics Branch


Genomic Functional Analysis Section


B.S. Pennsylvania State University, 1991

Ph.D. Pennsylvania State University, 1998


Laura Elnitski obtained her B.S. in molecular and cellular biology at The Pennsylvania State University (Penn State), with specialty research in chemical engineering. She obtained a Ph.D. in biochemistry and molecular biology, also at Penn State, while pursuing one of the first projects to look at multi-species comparisons of noncoding regulatory elements. She was awarded a Ruth L. Kirschstein National Research Service Award fellowship from the National Institutes of Health for postdoctoral training in the Department of Computer Science and Engineering at Penn State where she focused on the development and interpretation of multispecies genomic alignments to detect conserved regulatory regions.

Dr. Elnitski joined the National Human Genome Research Institute in 2005 as a tenure track investigator. She has participated in numerous genome sequencing projects including mouse, rat, cow and chicken, as well as the ENCODE Consortium to elucidate functional elements in the human genome. Her work specializes in developing tools to identify and discern the mechanistic action of functional elements in the human genome, including promoters, enhancers, silencers, splicing elements and epigenetic regulators. She received an Outstanding Research Achievement Award at the International Symposium on Bioinformatics, Research and Applications, Harvard University in 2007, and was selected for a Genome Technology International Young Investigator Award in 2009.

In 2013, Dr. Elnitski was awarded the Faculty Mentoring Award at NHGRI. She serves as a standing member of the Genomics and Computational Biology Study Section of the NIH.

Scientific Summary

The completion of the Human Genome Project was a pivotal step toward comprehensive annotation of genomic content, and opened the door for intensive studies of elusive functional elements. With a goal of identifying and characterizing noncoding regulatory elements involved in disease, Dr. Elnitski has been a member of the ENCODE Consortium since 2003, when it was initiated to catalog the content of regulatory regions of the human genome (see ENCODE publications in Science, Nature and PNAS). Since that time, Dr. Elnitski's research has pioneered both experimental and computational approaches to discern and validate uncharacterized regulatory components of the human genome. For example, to address the delicate interplay of silencing elements in regulating active gene expression, Dr. Elnitski developed a system to detect these elements in human sequences. The results were the first to show that negative-acting elements could be studied on a large scale in an efficient assay system (published in Genome Research).

Bidirectional promoters are now widely accepted as a mechanism of gene regulation. However in 2007, the basic set of genes with this type of regulatory structure, especially noncoding genes, was unknown. Dr. Elnitski's group elucidated this gene collection in several peer-reviewed publications (including PLoS Computational Biology and BMC Genomics and conference papers) showing the widespread and repeated occurrence of this regulatory structure. Moreover, by mapping these regulatory elements across five genomes, she and her group showed that bidirectional promoters are a basic regulatory component in mammalian transcriptional control, and that many bidirectional promoters are specific to a single species. Mapping of these uniquely occurring elements indicated the location of genomic rearrangements between species, and implicated the existence of species-specific transcripts. From this perspective, the group identified all such promoter regions that were unique to the human genome compared to other sequenced mammalian genomes and identified over 1,000 candidate human-specific genes (published in PLoS ONE).

heat map depicting the stratified levels of DNA methylation in a variety of gynecological tissues and tumors (from top to bottom, respectively)

Furthering the complexity of regulated gene expression, transcriptional splicing is an intricate and delicate process wherein mistakes can cause devastating diseases. By recognizing that splicing signals are mechanistically robust and utilize a set of common functional elements, Dr. Elnitski's group developed a new tool for elucidating unannotated splicing elements. This tool also predicts the consequences of sequence variants that change the sequence of these regulatory elements to disrupt normal splicing outcomes (published in Genome Biology). These tools emerged in time to support a new genomic paradigm, in which synonymous substitutions are increasingly recognized as disruptive events in regulated splicing scenarios. Dr. Elnitski has recently published a report on new synonymous mutations in CFTR, the gene responsible for cystic fibrosis, which likely play a role in etiology of the disease (published in Journal of Cystic Fibrosis). She also published a computational assessment of a recurrent synonymous driver mutation identified in melanoma (published in PNAS).

One of the most intriguing components of gene regulation is the epigenetic code, which influences gene expression from its positioning above the DNA sequence. Dr. Elnitski's group is studying altered epigenetic patterns of cancer samples to identify genomic loci that undergo aberrant regulation. Her work has identified genomic regions whose epigenetic state is commonly altered in epithelial tumors from 15 distinct types of cancer, providing a promising candidate for a predictive biomarker of disease (published in Epigenetics). In ongoing studies, she is pursuing the role of the methylator phenotype in tumors, characterized by extensive methylation of the tumor phenotype. The Elnitski group identified a methylator phenotype in endometrioid subtype ovarian tumors (published in PLoS ONE). Tumors with the methylator phenotype can be distinguished easily from other subtypes, and often have substantially different prognostic outcomes. Therefore, diagnostics based on DNA methylation patterns may provide efficient and economical avenues to personalized treatments. Furthermore, by studying DNA methylation profiles, Dr. Elnitski will be able to piece together the components of the functional pathways responsible for DNA methylation patterns in normal and abnormal conditions. These same ideas extend to the analysis of mouse models of human tumors. For example, one project in the lab examines the DNA methylation patterns in two versions of human endometrioid ovarian tumors, carrying PTEN-/- and APC-/- mutations or PTEN-/- APC-/- and ARID1A-/- mutations. The project addresses whether these tumors recapitulate the human phenotype, in which case they should show extensive aberrant DNA methylation.

These research projects are geared toward identifying and understanding regulatory mechanisms in a cell that could not be comprehensively addressed before the sequencing of the human genome. By studying the integrated picture of gene expression, DNA methylation and DNA mutation within a cell, Dr. Elnitski proposes to generate a comprehensive picture for elucidating disease mechanisms that encompasses cause-and-effect events.


Waterston RH, et al., including Elnitski L. Initial sequencing and comparative analysis of the mouse genome. Nature, 420: 520-562. 2002. [PubMed]

Gibbs RA, et al., including Elnitski L. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature, 428: 493-521. 2004. [PubMed]

The International Chicken Genome Consortium, Hillier, LW, et. al., including Elnitski L. Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature, 432(7018):695-716. 2004. [PubMed]

ENCODE Project Consortium. The ENCODE (ENCyclopedia Of DNA Elements) Project. Science, 306:636-640. 2004. [PubMed]

Giardine, B., Riemer, C., Hardison, R.C., Burhans, R., Elnitski, L., Shah, P., Zhang, Y., Blankenberg, D., Albert, I., Taylor, J., Miller, W., Kent, W.J., Nekrutenko, A. Galaxy: a platform for interactive large-scale genome analysis. Genome Res, 15:1451-5. 2005. [PubMed]

Elnitski, L., Jin, V.X., Farnham, P.J., Jones, S.J. Locating mammalian transcription factor binding sites: A survey of computational and experimental techniques. Genome Res, 16:1455-1464. 2006. [PubMed]

Petrykowska, H.M, Vockley, C.M., and Elnitski, L. Detection and characterization of silencers and enhancer-blockers in the greater CFTR locus. Genome Research, 18(8):1238-46. 2008. [PubMed]

Elsik CG, et al. including Elnitski L. The genome sequence of taurine cattle: a window to ruminant biology and evolution. Science, 324: 522-528. 2009. [PubMed]

Piontkivska H, Yang MQ, Larkin DM, Lewin HA, Reecy J, Elnitski L. Cross-species mapping of bidirectional promoters enables prediction of unannotated 5' UTRs and identification of species-specific transcripts. BMC Genomics, 10:189. 2009. [PubMed]

Bovine Genome Sequencing and Analysis Consortium, Elsik CG, Tellam RL, Worley KC, Gibbs RA, Muzny DM, Weinstock GM, Adelson DL, Eichler EE, Elnitski L, et al. The genome sequence of taurine cattle: a window to ruminant biology and evolution. Science, 324:522-8. 2009. [PubMed]

Woolfe A, Mullikin JC, Elnitski L. Genomic features defining exonic variants that modulate splicing. Genome Biol, 11(2):R20. 2010. [PubMed]

Kolbe DL, DeLoia JA, Porter-Gill P, Strange M, Guirguis A, Krivak TC, Brody LC, Elnitski L. Genomic analysis of site-specific DNA methylation patterns in primary epithelial ovarian cancers and endometrial metastases to the ovary. PLoS ONE, 7:e32941. 2012. [PubMed]

Scott, A, Petrykowska HM, Gotea V, Hefferon T, Elnitski L. Functional analysis of synonymous substitutions predicted to affect splicing of the CFTR gene. J. Cystic Fibrosis, 11:511-517. (Top 25 most downloaded paper April-June 2012.) 2012. [PubMed]

The ENCODE Project Consortium, including Elnitski L. An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57-74. 2012. [PubMed]

Laflamme K, Owen AN, Devlin EE, Yang MQ, Wong C, Steiner LA, Garrett LJ, Elnitski L, Gallagher PG, Bodine DM. Functional analysis of a novel cis-acting regulatory region within the human ankyrin gene (ANK-1) promoter. Mol Cell Biol, 30:3493-502. 2010. [PubMed]

ENCODE Project Consortium, et. al. including Elnitski, L. A user's guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol, 9:e1001046. 2011. [PubMed]

Gotea V, Petrykowska HM, Elnitski L. Bidirectional promoters as important drivers for the emergence of species-specific transcripts. PLoS One, 8:e57323. 2013. [PubMed]

Parker SCJ, Prickett TD Dutton-Regester K, Stitzel ML, Lin JC, Davis S, Simhadri VL, Jha S, Katagiri N, Gotea V, Teer JK, Xiaomu W, Morken MA, Bhanot UK, NISC Comparative Sequencing Program, Chen G, Elnitski LL, Davies MA, Gershenwald JE, Carter H, Karchin R, Robinson W, Robinson S, Rosenberg SA, Francis S. Collins FS, Parmigiani G, Komar AA, Kimchi-Sarfaty C, Hayward N, Margulies EH, and Samuels Y. Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma. Proc Natl Acad Sci, 110:13481-6. 2013. [PUbMed]

Sánchez-Vega F, Gotea V, Petrykowska HM, Margolin G, Krivak TC, DeLoia JA, Bell DW, Elnitski L. (2013) Recurrent patterns of DNA methylation in the ZNF154, CASP8, and VHL promoters across a wide spectrum of human solid epithelial tumors and cancer cell lines. Epigenetics, 8:1355-72. [PubMed]

Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A, Marinov GK, Ward LD, Birney E, Crawford GE, Dekker J, Dunham I, Elnitski LL, Farnham PJ, Feingold EA, Gerstein M, Giddings MC, Gilbert DM, Gingeras TR, Green ED, Guigo R, Hubbard T, Kent J, Lieb JD, Myers RM, Pazin MJ, Ren B, Stamatoyannopoulos JA, Weng Z, White KP, Hardison RC. Defining functional DNA elements in the human genome. Proc Natl Acad Sci, 111:6131-8. 2014. [PubMed]

Gotea V, Elnitski L. Ascertaining regions affected by GC-biased gene conversion through weak-to-strong mutational hotspots. Genomics, 103(5-6):349-56. 2014. [PubMed]

Gotea V, Gartner JJ, Qutob N, Elnitski L, Samuels Y. The functional relevance of somatic synonymous mutations in melanoma and other cancers. Pigment Cell Melanoma Res, doi: 10.1111/pcmr.12413. 2015. [PubMed]

Sánchez-Vega F, Gotea V, Margolin G, Elnitski L. (2015) Pan-cancer stratification of solid human epithelial tumors and cancer cell lines reveals commonalities and tissue-specific features of the CpG island methylator phenotype. Epigenetics Chromatin, 8:14. 2015. [PubMed]

Margolin G, Petrykowska HM, Jameel N, Bell DW, Young AC, Elnitski L. Robust Detection of DNA Hypermethylation of ZNF154 as a Pan-Cancer Locus with in Silico Modeling for Blood-Based Diagnostic Development. J Mol Diagn, (15)00274-3. 2016. [PubMed]

Book Chapters

Yang, M.Q., and Elnitski, L.L. Feature Characterization and Testing of Bidirectional Promoters in the Human Genome - Significance and Applications in Human Genome Research. Chapter 19 in Machine Learning in Bioinformatics, Yan-Qing Zhang and Jagath C. Rajapakse, eds. John Wiley & Sons, 2007.

Yang, M.Q. and Elnitski, L. A computational study of bidirectional promoters in the human genome. Bioinformatics Research and Applications, Zhang, Y., eds, Heidelberg, pp. 361-371. 2007.

Yang, M.Q. and Elnitski, L. Orthology of Bidirectional Promoters Enables Use of a Multiple Class Predictor for Discriminating Functional Elements in the Human Genome. Proceedings of the 2007 International Conference on Bioinformatics & Computational Biology. Arabnia, Yang, M.Q. and Yang, J.Y., eds. pp. 218-228. 2007.

Yang, M.Q., Taylor, J., and Elnitski, L. Rigorous Mapping of Orthologous Bidirectional Promoters in Vertebrates. Proceedings of Computations in Bioinformatics and Bioscience. BMC Bioinformatics Suppl. Issue. pp. 115-122. 2008.

Elnitski L, Burhans R, Riemer C, Hardison R, Miller W. MultiPipMaker: A comparative alignment server for multiple DNA sequences. Current Protocols in Bioinformatics. Wiley & Sons Inc., pp. 10.4.1-10.4.14. 2010.

Welch LR, Koehly LM, Elnitski L. Shared regulatory motifs in promoters of human DNA repair genes. DNA Repair / Book 4, Inna Kruman (Ed.), InTech Publishers. 2011.

Genomic Functional Analysis Section Staff

Valer Gotea
Valer Gotea, Ph.D.
  • Staff Scientist
  • Genomic Functional Analysis Section
Gennady Margolin
Gennady Margolin, Ph.D.
  • Contractor
  • Genomic Functional Analysis Section
Hania Petrykowska
Hania Petrykowska
  • Biologist
  • Genomic Functional Analysis Section
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Brenna A. Labarre
  • Dissertation Student
  • Genomic Functional Analysis Section

Last updated: January 5, 2015