Science

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 understand the regulatory wiring of the genome. This includes >2 million noncoding regulatory elements that control how different combinations of our 21,000 genes are expressed in different cell types and states. Importantly, these regulatory elements harbor >100,000 genetic variants that influence common human diseases and traits — including hundreds of variants each for autoimmune and inflammatory diseases like inflammatory bowel disease, multiple sclerosis, and type 1 diabetes. I use a combination of experimental and computational genomics, biochemistry, immunology, and human genetics to assemble regulatory maps of the human genome and uncover mechanisms that control risk for autoimmune and inflammatory diseases. Understanding these mechanisms may enable us to manipulate the regulatory sequences in our genomes to develop new treatments for immune diseases.

Please contact me if you are interested in joining the team.

See my full publication list on PubMed.

Selected Publications:

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] [AddGene plasmids]

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]

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]

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] [see Guttman Lab for additional RAP protocols].

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].

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]

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, 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]

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]

Talks:

Principles of Enhancer Function from Thousands of CRISPR Perturbations. Selected talk at Keystone: Gene Control, Whistler, Canada. Mar 2018.

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.

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.

Mechanisms for regulatory crosstalk between neighboring genes in mammals. Selected talk at Noncoding RNAs in Health and Disease, Santa Fe, NM. Feb 2016.

Many promoters of lncRNAs and mRNAs act as enhancers in local gene regulatory networks. Selected talk at Epigenomics 2016, Puerto Rico. Jan 2016.

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.

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]

RNA Antisense Purification (RAP) identifies novel mechanisms of lncRNA localization to chromatin.  Selected talk at Epigenetics & Chromatin, Boston, MA.  March 2013.

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