Laura Elnitski, Ph.D.

Senior Investigator

Genomic Functional Analysis Section

Head

Genomic Functional Analysis Section

Education

B.S. Pennsylvania State University

Ph.D. Pennsylvania State University

Contact Info

BG 49 RM 4C08
49 CONVENT DR
BETHESDA MD 20892

Biography

Dr. Laura Elnitski is a recognized leader in functional genomics and computational biology, specializing in the identification of regulatory elements in the human genome and their role in disease. She earned her Ph.D. in Biochemistry and Molecular Biology from The Pennsylvania State University and completed a postdoctoral fellowship in computational genomics through the prestigious Ruth L. Kirschstein National Research Service Award (F32). She joined the National Human Genome Research Institute (NHGRI) in 2005 as a tenure-track investigator and was awarded tenure in 2012.

Dr. Elnitski has played a pivotal role in major genome sequencing and analysis initiatives, including the ENCODE Consortium, the CAGI Consortium, and genome sequencing projects for the mouse, chicken, bovine, and rat genomes. Beyond her research, she has held key leadership positions at the NIH, serving on the NIH Central Tenure Committee, co-directing the Georgetown-NIH Graduate Partnerships Program (GPP), and leading NIH Faculty Search Committees. She has also contributed significantly to NIH extramural funding decisions, serving as a permanent member and chair of study sections focused on Genomics, Computational Biology, and Technology.

Her contributions to education and mentorship have been recognized with mentoring awards from NHGRI and NIH, and her lectures are integral to cancer systems biology training at leading institutions. Her groundbreaking work in cancer diagnostics, ADHD, and genome biology has been featured in over 50 international news outlets. Through her dedication to mentorship and leadership, Dr. Elnitski continues to train the next generation of genomic scientists while advancing genome biology, precision medicine and biomarker discovery.

Biography

Dr. Laura Elnitski is a recognized leader in functional genomics and computational biology, specializing in the identification of regulatory elements in the human genome and their role in disease. She earned her Ph.D. in Biochemistry and Molecular Biology from The Pennsylvania State University and completed a postdoctoral fellowship in computational genomics through the prestigious Ruth L. Kirschstein National Research Service Award (F32). She joined the National Human Genome Research Institute (NHGRI) in 2005 as a tenure-track investigator and was awarded tenure in 2012.
Dr. Elnitski has played a pivotal role in major genome sequencing and analysis initiatives, including the ENCODE Consortium, the CAGI Consortium, and genome sequencing projects for the mouse, chicken, bovine, and rat genomes. Beyond her research, she has held key leadership positions at the NIH, serving on the NIH Central Tenure Committee, co-directing the Georgetown-NIH Graduate Partnerships Program (GPP), and leading NIH Faculty Search Committees. She has also contributed significantly to NIH extramural funding decisions, serving as a permanent member and chair of study sections focused on Genomics, Computational Biology, and Technology.
Her contributions to education and mentorship have been recognized with mentoring awards from NHGRI and NIH, and her lectures are integral to cancer systems biology training at leading institutions. Her groundbreaking work in cancer diagnostics, ADHD, and genome biology has been featured in over 50 international news outlets. Through her dedication to mentorship and leadership, Dr. Elnitski continues to train the next generation of genomic scientists while advancing genome biology, precision medicine and biomarker discovery.

Scientific Summary

Dr. Laura Elnitski’s research integrates genomics, epigenetics, and transcriptomics to uncover gene regulatory mechanisms that drive disease progression and therapeutic resistance. A central focus is the intersection of DNA methylation, RNA splicing, and chromatin architecture in shaping gene regulation in genetic diseases and cancer. This work advances knowledge at the forefront of splicing, chromatin dynamics, and biomarker discovery, providing critical insights into oncogenesis and disease mechanisms.

Her research helped identify Suppression of Splicing (SOS), an RNA quality control mechanism that prevents premature stop codons, ensuring genome integrity by protecting protein synthesis from disruptive errors. This discovery highlights a fundamental process in maintaining genomic stability and preventing disease. Additional findings include computational methods for defining transcript isoform frameworks and their application to tumor stratification, linking splicing alterations to melanoma metastasis and the classification of new molecular subtypes for improving patient outcomes. Expanding on this, mapping of splicing networks across 33 cancer types and 11,000 tumors has demonstrated how mutations disrupt transcriptional circuits, refining models of gene regulation and cellular information flow critical to precision medicine.

Building on transcriptomic insights, investigations into chromatin dynamics have uncovered epigenetic regulators of aggressive ovarian cancer, leading to the discovery of Megacomplex, a chromatin structure that protects the estrogen receptor (ERα) from therapeutic degradation. Targeting Megacomplex with JQ1, a small molecule that disassembles chromatin, restored ERα accessibility, presenting a novel therapeutic approach. Further studies on genome silencers identified super-silencer structures, expanding understanding of tumor-suppressive gene regulation and informing potential therapeutic reactivation strategies.

These discoveries translate into clinically useful applications, driving the development of epigenetic and transcriptomic biomarkers for non-invasive cancer detection. A pan-cancer DNA methylation biomarker for plasma-based screening has enhanced early detection capabilities, while refined biomarker panels improve the sensitivity and specificity of blood-based cancer diagnostics, with broad implications for population screening and early intervention.

By integrating genomic, epigenetic, and transcriptomic data, this research continues to refine the understanding of regulatory mechanisms governing disease progression, informing targeted therapeutic strategies and advancing precision oncology and biomarker-driven medicine.

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

Publications

Huang D, Petrykowska HM, Miller BF, Elnitski L, Ovcharenko I. Identification of human silencers by correlating cross-tissue epigenetic profiles and gene expression. Genome Res. 2019 Apr;29(4):657-667. doi: 10.1101/gr.247007.118. Epub 2019 Mar 18.

Gotea V, Margolin G, Elnitski L. CAGI experiments: Modeling sequence variant impact on gene splicing using predictions from computational tools. Hum Mutat. 2019 Sep;40(9):1252-1260. doi: 10.1002/humu.23782. Epub 2019 Jun 27.

Chen YC, Elnitski L. Aberrant DNA methylation defines isoform usage in cancer, with functional implications. PLoS Comput Biol. 2019 Jul 22;15(7):e1007095. doi: 10.1371/journal.pcbi.1007095.

LaBarre BA, Goncearenco A, Petrykowska HM, Jaratlerdsiri W, Bornman MSR, Hayes VM, Elnitski L. MethylToSNP: identifying SNPs in Illumina DNA methylation array data. Epigenetics Chromatin. 2019 Dec 20;12(1):79. doi: 10.1186/s13072-019-0321-6.

Goncearenco A, LaBarre BA, Petrykowska HM, Jaratlerdsiri W, Bornman MSR, Turner SD, Hayes VM, Elnitski L. DNA methylation profiles unique to Kalahari KhoeSan individuals. Epigenetics. 2021 May;16(5):537-553. doi: 10.1080/15592294.2020.1809852. Epub 2020 Sep 6.

Miller BF, Pisanic Ii TR, Margolin G, Petrykowska HM, Athamanolap P, Goncearenco A, Osei-Tutu A, Annunziata CM, Wang TH, Elnitski L. Leveraging locus-specific epigenetic heterogeneity to improve the performance of blood-based DNA methylation biomarkers. Clin Epigenetics. 2020 Oct 20;12(1):154. doi: 10.1186/s13148-020-00939-w.

Miller BF, Petrykowska HM, Elnitski L. Assessing ZNF154 methylation in patient plasma as a multicancer marker in liquid biopsies from colon, liver, ovarian and pancreatic cancer patients. Sci Rep. 2021 Jan 8;11(1):221. doi: 10.1038/s41598-020-80345-7.

Li Y, Jaiswal SK, Kaur R, Alsaadi D, Liang X, Drews F, DeLoia JA, Krivak T, Petrykowska HM, Gotea V, Welch L, Elnitski L. Differential gene expression identifies a transcriptional regulatory network involving ER-alpha and PITX1 in invasive epithelial ovarian cancer. BMC Cancer. 2021 Jul 3;21(1):768. doi: 10.1186/s12885-021-08276-8.

Shefer K, Boulos A, Gotea V, Arafat M, Ben Chaim Y, Muharram A, Isaac S, Eden A, Sperling J, Elnitski L, Sperling R. A novel role for nucleolin in splice site selection. RNA Biol. 2022;19(1):333-352. doi: 10.1080/15476286.2021.2020455. Epub 2021 Dec 31.

Holland DO, Gotea V, Fedkenheuer K, Jaiswal SK, Baugher C, Tan H, Fedkenheuer M, Elnitski L. Characterization and clustering of kinase isoform expression in metastatic melanoma. PLoS Comput Biol. 2022 May 13;18(5):e1010065. doi: 10.1371/journal.pcbi.1010065.

Sudre G, Gildea DE, Shastri GG, Sharp W, Jung B, Xu Q, Auluck PK, Elnitski L, Baxevanis AD, Marenco S, Shaw P. Mapping the cortico-striatal transcriptome in attention deficit hyperactivity disorder. Mol Psychiatry. 2023 Feb;28(2):792-800. doi: 10.1038/s41380-022-01844-9. Epub 2022 Nov 16.

Funderburk K, Bang-Christensen SR, Miller BF, Tan H, Margolin G, Petrykowska HM, Baugher C, Farney SK, Grimm SA, Jameel N, Holland DO, Altman NS, Elnitski L. Evaluating Stacked Methylation Markers for Blood-Based Multicancer Detection. Cancers (Basel). 2023 Oct 1;15(19):4826. doi: 10.3390/cancers15194826.

Critical Assessment of Genome Interpretation Consortium including Elnitski L. CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods. Genome Biol. 2024 Feb 22;25(1):53. doi: 10.1186/s13059-023-03113-6.

Shastri GG, Sudre G, Ahn K, Jung B, Kolachana B, Auluck PK, Elnitski L, Marenco S, Shaw P. Cortico-striatal differences in the epigenome in attention-deficit/ hyperactivity disorder. Transl Psychiatry. 2024 Apr 11;14(1):189. doi: 10.1038/s41398-024-02896-x.

Huang D, Petrykowska HM, KumarD, Afzali B, Elnitski L, and OvcharenkoI. Super-silencers are crucial for development and carcinogenesis (under revision).

Jaiswal SK, Fedkenheuer K, Khamar R, Tan H, Gotea V, Raj S, Fedkenheuer M, Elkahloun A, Zhao M, Jenkins LM, Annunziata CM, Elnitski L. The Megacomplex protects ER-alpha from degradation by Fulvestrant in epithelial ovarian cancer. Cancer Lett. 2025 Jan 1;608:217129. doi: 10.1016/j.canlet.2024.217129. Epub 2024 Jul 22.

Shastri GG, Sudre G, Ahn K, Jung B, Kolachana B, Auluck PK, Elnitski L, Shaw P. Examining epigenetic aging in the post-mortem brain in attention deficit hyperactivity disorder. Front Genet. 2024 Oct 8;15:1480761. doi: 10.3389/fgene.2024.1480761.

Fedkenheuer M, Shang Y, Jung S, Fedkenheuer K, Park S, Mazza D, Sebastian R, Nagashima H, Zong D, Tan H, Jaiswal SK, Fu H, Cruz A, Vartak SV, Wisniewski J, Sartorelli V, O'Shea JJ, Elnitski L, Nussenzweig A, Aladjem MI, Meng FL, Casellas R. A dual role of Cohesin in DNA DSB repair. Nat Commun. 2025 Jan 20;16(1):843. doi: 10.1038/s41467-025-56086-4.

Tan H, Gotea V, Seidel NE, Holland DO, Fedkenheuer K, Jaiswal SK, Bang-Christensen S, and Elnitski L. iSoMAS: Finding somatic mutations associated with alternative splicing in human cancers (in press, PLoS computational Biology, 2025).

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.