Our genomes – three billion base pairs of genetic code – encode the molecular information that gives rise to life, yet we are just beginning to unravel how this information is organized, interpreted, and regulated. Building on advances in genomics that bring the power of big data to bear on biology, I seek to uncover molecular mechanisms of gene regulation. I use a combination of biochemistry, genetics, and computational biology to dissect the functions of noncoding RNAs, enhancers, and genome architecture. Understanding the fundamental processes by which these cellular machines operate may enable us to manipulate the processes that interpret our genome sequence, with the ultimate goal of developing new treatments for human disease.
Please contact me if you are interested in joining the team.
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Joung J, Engreitz JM, Konermann S, Abudayyeh OA, Verdine VK, Aguet F, Gootenberg JS, Sanjana NE, Wright JB, Fulco CP, Tseng YY, Yoon CH, Bohem JS, Lander ES, and Zhang F. Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood. Nature, Aug 2017. [web]
Gupta RM, Hadaya J, Trehan A, Zekavat SM, Roselli C, Klarin D, Emdin C, Hilvering CRE, Bianchi V, Mueller C, Khera AV, Ryan RJH, Engreitz JM, Issner R, Epstein C, Brown J, Bernstein BE, de Laat W, Katherisan S. A genetic variant associated with five vascular diseases is a distal regulator of Endothelin-1 gene expression. Cell, July 2017. [web]
Rheinbay E, Parasuraman P, Grimsb J, Tiao G, Engreitz JM, Kim J, Lawrence MS, Taylor-Weiner A, Rodriguez-Cuevas S, Rosenberg M, Hess J, Stewart C, Maruvka YE, Stojanov P, Cortes ML, Seepo S, Cibulskis C, Tracy A, Pugh TJ, Lee J, Zheng Z, Ellisen LW, Iafrate AJ, Boehm JA, Gabriel SB, Meyerson ML, Golub TR, Baselga J, Hidalgo-Miranda A, Shioda T, Bernards A, Lander ES, and Getz G. Recurrent and functional regulatory mutations in breast cancer. Nature, July 2017. [web]
Grossman SR, Zhang X, Wang L, Engreitz JM, Melnikov A, Rogov P, Tewhey R, Isakova A, Deplancke B, Bernstein BE, Regev A, Mikkelsen TS, and Lander ES. Systematic dissection of genomic features determining transcription factor binding and enhancer function. Proc Nat Acad Sci, Jan 2017. [web]
Engreitz JM, Haines JE, Munson G, Chen J, Perez EM, Kane M, McDonel PE, Guttman M, and Lander ES. Local regulation of gene expression by lncRNA promoters, transcription, and splicing. Nature, Oct 2016. [web]
Engreitz JM*, Ollikainen N*, and Guttman M. Long non-coding RNAs (lncRNAs) as spatial amplifiers that control nuclear architecture and gene expression. Nat Rev Mol Cell Biol, Oct 2016. [web]
Moynihan KD*, Opel CF*, Szeto GL, Tzeng A, Zhu ER, Engreitz JM, Williams RT, Rakhra K, Zhang MH, Rothschilds AM, Kumari S, Kelly RL, Kwan BH, Abraham W, Hu K, Mehta NK, Kauke MJ, Suh H, Cochran JR, Lauffenburger DA, Wittrup KD, and Irvine DJ. Eradication of large established tumors by combination immunotherapy engaging innate and adaptive immunity. Nat Med, Oct 2016. [web]
Fulco CP, Munschauer M, Anyoha R, Munson G, Grossman SR, Perez EM, Kane M, Cleary B, and Lander ES*, Engreitz JM*. Systematic mapping of functional enhancer-promoter connections with CRISPR interference. Science, 10.1126/science.aag2445, Sep 2016. [web]
Engreitz JM, Lander ES*, and Guttman M*. RNA Antisense Purification (RAP) for mapping RNA interactions with chromatin. Methods Mol Biol 1262:183-197 (2015). [web]
Engreitz JM, Sirokman K, McDonel P, Shishkin A, Surka C, Russell P, Grossman SR, Chow AY, Guttman M*, and Lander ES*. RNA-RNA interactions enable specific targeting of noncoding RNAs to nascent pre-mRNAs and chromatin sites. Cell 159(1):188-199 (2014). [web] [protocols] [data] [Highlight in Nature Reviews Genetics].
Schwartz S, Bernstein DA, Mumbach MR, Jovanovic M, Herbst RH, Leon-Ricardo, Engreitz JM, Guttman M, Satija R, Lander ES*, Fink G*, and Regev A*. Transcriptome-wide mapping reveals widespread dynamic regulated pseudouridylation of ncRNA and mRNA. Cell 159(1):148-162 (2014). [web]
Hacisuleyman E, Goff LA, Trapnell C, Williams A, Henao-Mejia J, Sun L, McClanahan P, Hendrickson DG, Sauvageau M, Kelley DR, Morse M, Engreitz J, Lander ES, Guttman M, Lodish HF, Flavell R, Raj A, and Rinn JL. Topological organization of multi-chromosomal regions by Firre. Nat Struct Mol Bio, 21(2):198-206 (2014). [web]
Lee CY, Lin Y, Bratman S, Feng W, Kuo A, Scheeren F, Engreitz JM, Varma S, West R, and Diehn M. Neuregulin autocrine signaling promotes self-renewal of breast tumor-initiating cells by triggering HER2/HER3 activation. Cancer Res 74(1):314-352 (2013). [web]
Engreitz JM, Pandya-Jones A, McDonel P, Shishkin A, Surka C, Sirokman K, Kadri S, Xing J, Goren A, Lander ES*, Plath K*, and Guttman M*. The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome. Science 341:1237973 (2013). [web] [Perspective in Science] [protocols] [data]
Engreitz JM*, Agarwala V*, and Mirny LA. Three Dimensional Genome Architecture Influences Partner Selection for Chromosomal Translocations in Human Disease. PLOS ONE 7(9):e44196 (2012). [web] [PLOS ONE Blog]
Engreitz JM, Chen R, Morgan AA, Dudley JT, Mallelwar R, and Butte AJ. ProfileChaser: searching microarray repositories based on genome-wide patterns of differential expression. Bioinformatics 27(23):3317-8 (2011). [ProfileChaser] [web]
Zhu H, Shyh-Chang N, Segré AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, Urbach A, Thornton JE, Triboulet R, Gregory RI, DIAGRAM Consortium, MAGIC Investigators, Altshuler D, and Daley GQ. The Lin28/let-7 Axis Regulates Glucose Metabolism. Cell, 147(1):81-94 (2011). [web]
Engreitz JM, Morgan AA, Dudley JT, Chen R, Thathoo R, Altman RB, and Butte AJ. Content-based microarray search with differential expression profiles. BMC Bioinformatics, 11(1):603 (2010). [web]
Engreitz JM, Daigle BJ Jr, Marshall JJ, and Altman RB. Independent component analysis: Mining microarray data for fundamental human gene expression modules. J Biomed Inform, 43(6):923-944 (2010). [web]
Engreitz JM, Fulco CP, Haines JE, Munson G, Perez EM, Anyoha R, Kane M, Grossman SR, and Lander ES. Quantitative control of enhancer function by 3D chromosome conformation. Selected talk at Systems Biology: Global Regulation of Gene Expression, Cold Spring Harbor, NY. Feb 2017.
Engreitz JM, Haines JE, Munson G, Kane M, McDonel P, Guttman M, and Lander ES. Many promoters of lncRNAs and mRNAs act as enhancers in local gene regulatory networks. Selected talk at Systems Biology: Global Regulation of Gene Expression, Cold Spring Harbor, NY. Mar 2016.
Engreitz JM, Haines JE, Munson G, Kane M, McDonel P, Guttman M, and Lander ES. Mechanisms for regulatory crosstalk between neighboring genes in mammals. Selected talk at Noncoding RNAs in Health and Disease, Santa Fe, NM. Feb 2016.
Engreitz JM, Haines JE, Munson G, Kane M, McDonel P, Guttman M, and Lander ES. Many promoters of lncRNAs and mRNAs act as enhancers in local gene regulatory networks. Selected talk at Epigenomics 2016, Puerto Rico. Jan 2016.
Engreitz JM, Pandya-Jones A, McDonel P, Shishkin A, Surka C, Sirokman K, Kadri S, Plath K, Lander ES*, and Guttman M*. Large noncoding RNAs can localize to regulatory DNA targets by exploiting the three-dimensional architecture of the genome. Selected talk at Chromatin Structure & Function, Grand Cayman. Oct 2013.
Engreitz JM, Pandya-Jones A, McDonel P, Shishkin A, Surka C, Sirokman K, Kadri S, Plath K, Lander ES*, and Guttman M*. Large noncoding RNAs can localize to regulatory DNA targets by exploiting the three-dimensional architecture of the genome. Selected talk at The Biology of Genomes, Cold Spring Harbor, NY. May 2013. [video] [Review in Science]
Engreitz JM, McDonel P, Shishkin A, Surka C, Sirokman K, Lander ES*, and Guttman M*. RNA Antisense Purification (RAP) identifies novel mechanisms of lncRNA localization to chromatin. Selected talk at Epigenetics & Chromatin, Boston, MA. March 2013.