Mitchell Guttman

Assistant Professor of Biology; Investigator, Heritage Medical Research Institute
B.S., University of Pennsylvania, 2006; M.S., 2006; Ph.D., Massachusetts Institute of Technology, 2012. Visiting Associate, Caltech, 2012-13; Assistant Professor, 2013-; HMRI Investigator, 2015-.

Over the past decade, it has become clear that mammalian genomes encode thousands of long non-coding RNAs (lncRNAs), many of which are now implicated in diverse biological processes. Our lab aims to understand the mechanisms by which lncRNAs act to control cellular functions. Specifically, we aim to understand how lncRNAs can regulate gene expression by coordinating regulatory proteins, localizing to genomic DNA targets, and shaping three-dimensional (3D) nuclear organization.

Selected Publications 

Chen CK, Blanco M, Jackson C, Aznauryan E, Ollikainen N, Surka C., Chow A, Cerase A, McDonel P, Guttman M (2016). Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing. Science doi:10.1126/science.aae0047

McHugh CA, Chen CK, Chow A, Surka CF, Tran C, McDonel P, Pandya-Jones A, Blanco MR, Burghard C, Moradian A, Sweredoski MJ, Shishkin AA, Su J, Lander ES, Hess S, Plath K, and Guttman M (2015). The Xist lncRNA directly interacts with SHARP to silence transcription through HDAC3. Nature doi:10.1038/nature14443

Shishkin AA, Giannoukos G, Kucukural A, Ciulla D, Busby M, Surka CF, Chen J, Bhattacharyya RP, Rudy RF, Patel MM, Novod N, Hung DT, Gnirke A, Garber M, Guttman M*†, Jonathan Livny* (2015). Simultaneous generation of large numbers of strand-specific RNA-Seq cDNA libraries in a single reaction. Nature Methods doi: 10.1038/nmeth.3313

Engreitz JM, Lander ES, and Guttman M (2015). RNA Antisense Purification (RAP) for mapping RNA interactions with chromatin. Methods in Molecular Biology 1262:183-97

Rinn JL and Guttman M (2014). RNA and the dynamics of nuclear organization. Science 345(6202):1240-1

Quinodoz S and Guttman M (2014). Long non-coding RNAs: An emerging link between gene regulation and nuclear organization. Trends in Cell Biology 24(11): 651–663

Engreitz JM, Sirokman K, McDonel P, Shishkin A, Surka CF, Russell P, Grossman SR, Chow AY, Guttman M*†, Lander ES* (2014). RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites. Cell Sep 25;159(1):188-99

McHugh CA, Russell P, and Guttman M (2014). Methods for comprehensive experimental identification of RNA–protein interactions. Genome Biology 15(1):203

Engreitz JM, Pandya-Jones A, McDonel P, Shishkin A, Sirokman K, Surka C, Kadri S, Lander ES, Plath K, and Guttman M (2013). The Xist lncRNA exploits three-dimensional chromosome architecture to spread across the X-chromosome. Science 341:767

Guttman M, Russell P, Ingolia NT, Weissman JS, and Lander ES (2013). Ribosome profiling provides evidence that large non-coding RNAs do not encode proteins. Cell 154(1):240-51

Guttman M and Rinn JL. (2012). Modular regulatory principles of large non-coding RNAs. Nature 482(7385):339-46

Guttman M, Donaghey J, Carey BW, Garber M,  Grenier J, Munson G, Young G,  Lucas AB, Ach R, Bruhn L, Yang X, Amit I, Meissner A, Regev A, Rinn JL, Root DE, Lander ES. (2011). lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477(7364):295-300

Garber M, Grabherr MG, Guttman M, Trapnell C. (2011). Computational methods for transcriptome annotation and quantification using RNA-Seq. Nature Methods 8(6):469-77

Guttman M, Garber M, Levin JZ, Donaghey J, Robinson J, Adiconis X, Fan L, Koziol MJ, Gnirke A, Nusbaum C,  Rinn JL, Lander ES, Regev A. (2010) Ab initio reconstruction of transcriptomes of pluripotent and lineage committed cells reveals gene structures of thousands of lincRNAs. Nature Biotechnology 28(5):503-10

Guttman M, Amit I, Garber M, French C, Lin M, Feldser D, Huarte M, Cabili M, Carey BW, Cassady J, Jaenisch R,  Mikkelsen T, Jacks T, Hacohen N, Bernstein BEB, Kellis M, Regev A, Rinn JL, Lander ES. (2009) Chromatin signature reveals over a thousand highly conserved, large non-coding RNAs in mammals. Nature 458(7235):223-7

Guttman M, Mies C, Dudycz-Sulicz K, Diskin SJ, Baldwin DA, Grant GR. (2007) Assessing the Significance of Conserved Genomic Aberrations Using High Resolution Genomic Microarrays. PLoS Genetics 3(8):e143

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