Picture of Karen Adelman
Karen Adelman, Ph.D.
Professor of Biological Chemistry and Molecular Pharmacology

The Adelman laboratory investigates the dynamic interplay between signals from the environment and transcription by RNA polymerase II (Pol II).

Karen Adelman earned her Ph.D. in 1999 from Universite de Paris VI, working at the Institut Pasteur under a fellowship from the National Science Foundation. She then joined the laboratory of John Lis, Ph.D., at Cornell University for her post-doctoral training. In 2005, she established her own laboratory at the National Institute of Environmental Health Sciences (NIH), and was promoted to Senior Investigator in 2011.  In 2016, she joined the Harvard Medical School faculty as a Professor in the Department of Biological Chemistry and Molecular Pharmacology.

 

Research:

The Adelman laboratory investigates the dynamic interplay between signals from the environment and transcription by RNA polymerase II (Pol II). The ability to rapidly integrate multiple extra- and intra-cellular cues to produce specific patterns of gene expression is essential for the growth, development, and survival of all organisms; however, the molecular mechanisms leading from these signals to the coordinated activation of gene networks are not well understood. The group uses genomic approaches in Drosophila and murine model systems to measure changes in Pol II distribution, gene expression, and epigenetic chromatin signatures that occur when a cell receives specific stimuli from the environment. The mechanisms underlying these changes are then probed using a combination of genetic and biochemical techniques.

In particular, the Adelman group is investigating how gene networks can be tuned to respond in a rapid yet balanced manner to signals elicited during development or immune challenge. By elucidating how cells dynamically react to external stimuli, this work provides new insights into gene-environment interactions. Moreover, since transcription dysregulation during such responses contributes to the etiology of numerous disease states including chronic inflammation and cancer, this work aims to identify novel targets or approaches for treating disease.

Adelman's group has pioneered global studies of Pol II pausing during early transcription elongation. Pausing, and the regulated release of Pol II into productive RNA synthesis have emerged as central aspects of gene regulation in metazoans, fueling great interest in better understanding this process.

The Adelman lab also uncovered a surprising interplay between paused Pol II and chromatin structure, wherein pausing facilitates gene activity by establishing and maintaining and accessible chromatin architecture around promoters. Ongoing work probes the importance of this feature of paused Pol II at non-coding loci such as enhancers.

Work from the lab has revealed that regulated pausing of Pol II governs expression of many genes in signal-responsive pathways. Accordingly, we have found that release of paused Pol II into productive elongation is a key step controlling the expression of signal-responsive genes such as proinflammatory cytokines and regulators of FGF signaling. Notably, pausing controls the basal expression of critical hubs in signaling networks, tuning cellular responsiveness to inflammatory cues, and defining the differentiation potential of mouse embryonic stem cells.

Ongoing work will further explore the interactions between pausing and epigenetic features of the genome, as well as the impact of pausing on tuning the transcriptional dynamics of gene networks during differentiation and development. Approaches include cutting-edge genomic and bioinformatic strategies to further elucidate gene regulation at promoters and enhancers, and mouse models of inflammation and development to investigate the physiological roles of pausing.

Address: 

LHRRB Building, Room 201A

45 Shattuck Street

Boston, MA 02115

Publications View
The Integrator Complex Attenuates Promoter-Proximal Transcription at Protein-Coding Genes.
Authors: Authors: Elrod ND, Henriques T, Huang KL, Tatomer DC, Wilusz JE, Wagner EJ, Adelman K.
Mol Cell
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The Histone Deacetylase SIRT6 Restrains Transcription Elongation via Promoter-Proximal Pausing.
Authors: Authors: Etchegaray JP, Zhong L, Li C, Henriques T, Ablondi E, Nakadai T, Van Rechem C, Ferrer C, Ross KN, Choi JE, Samarakkody A, Ji F, Chang A, Sadreyev RI, Ramaswamy S, Nechaev S, Whetstine JR, Roeder RG, Adelman K, Goren A, Mostoslavsky R.
Mol Cell
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PCIF1 Catalyzes m6Am mRNA Methylation to Regulate Gene Expression.
Authors: Authors: Sendinc E, Valle-Garcia D, Dhall A, Chen H, Henriques T, Navarrete-Perea J, Sheng W, Gygi SP, Adelman K, Shi Y.
Mol Cell
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Promoter-proximal pausing of RNA polymerase II: a nexus of gene regulation.
Authors: Authors: Core L, Adelman K.
Genes Dev
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NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region.
Authors: Authors: Oldfield AJ, Henriques T, Kumar D, Burkholder AB, Cinghu S, Paulet D, Bennett BD, Yang P, Scruggs BS, Lavender CA, Rivals E, Adelman K, Jothi R.
Nat Commun
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Negative elongation factor is essential for endometrial function.
Authors: Authors: Hewitt SC, Li R, Adams N, Winuthayanon W, Hamilton KJ, Donoghue LJ, Lierz SL, Garcia M, Lydon JP, DeMayo FJ, Adelman K, Korach KS.
FASEB J
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Emerging Roles of Non-Coding RNA Transcription.
Authors: Authors: Kaikkonen MU, Adelman K.
Trends Biochem Sci
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Numerous recursive sites contribute to accuracy of splicing in long introns in flies.
Authors: Authors: Pai AA, Paggi JM, Yan P, Adelman K, Burge CB.
PLoS Genet
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Transcriptional speed bumps revealed in high resolution.
Authors: Authors: Adelman K, Henriques T.
Nature
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Transcription start site profiling uncovers divergent transcription and enhancer-associated RNAs in Drosophila melanogaster.
Authors: Authors: Meers MP, Adelman K, Duronio RJ, Strahl BD, McKay DJ, Matera AG.
BMC Genomics
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