Picture of Kevin Struhl

Kevin Struhl, Ph.D.

David Wesley Gaiser Professor of Biological Chemistry and Molecular Pharmacology
617-432-2104
Struhl lab website

We combine genetic, molecular, biochemical, genomic, and evolutionary approaches to study the mechanistic relationship between chromatin structure and transcriptional regulation and its implications for epigenetic inheritance of heterochromatin.  In addition, we combine functional genomic and mechanistic approaches to elucidate the transcriptional regulatory circuits involved in the process of cellular transformation and formation of cancer stem cells, and the use of metformin as an anti-cancer drug in combination with chemotherapy.

Research:

Transcriptional regulation in response to environmental and developmental cues is mediated by the combinatorial and synergistic action of specific DNA-binding activators and repressors on components of the general transcription machinery and chromatin modifying activities, and it also involves microRNAs.  We combine genetic, molecular, genomic, and evolutionary approaches to address fundamental questions about transcriptional regulatory mechanisms, mRNA stability, and 3’ end formation in yeast, as well as elucidating the transcriptional regulatory circuits that mediate the process of cellular transformation and formation of cancer stem cells.

Relationship between transcriptional regulatory mechanisms and chromatin structure in yeast: Current projects include 1) how co-activators, chromatin-modifying complexes, repressors, and components of the basic transcription machinery are recruited to promoters in vivo under genetically and environmentally defined conditions, 2) intrinsic and dynamic aspects of chromatin structure, and mechanisms of epigenetic inheritance of heterochromatic and euchromatic states, 3) distinguishing between biological function and biological noise using evolutionarily related yeast species and other approaches.

mRNA stability and 3’ end formation in yeast:  Current projects include 1) selection of polyadenylation sites, 2) mechanism of mRNA decay including the identification of stabilizing and destabilizing sequences and the role of secondary structure, 3) regulation of 3’ end formation and mRNA stability under different environmental conditions by RNA-binding proteins

Transcriptional regulatory circuits during the process of cellular transformation in human cells:  Current projects include 1) an epigenetic switch from non-transformed to transformed cells in response to a transient inflammatory signal, 2) molecular pathways required for the formation of cancer stem cells, 3) defining an inflammatory index to type human cancers, 4) phenotypic screening methods for personalized therapy for human cancer patients, 5) testing metformin as a potential anti-cancer drug.

Address: 

Room C-351A

240 Longwood Ave.

Boston, MA 02115

Publications View
Differential analysis for high density tiling microarray data.
Authors: Authors: Ghosh S, Hirsch HA, Sekinger EA, Kapranov P, Struhl K, Gingeras TR.
BMC Bioinformatics
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Nucleosome positioning signals in genomic DNA.
Authors: Authors: Peckham HE, Thurman RE, Fu Y, Stamatoyannopoulos JA, Noble WS, Struhl K, Weng Z.
Genome Res
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Genomic analysis of protein-DNA interactions in bacteria: insights into transcription and chromosome organization.
Authors: Authors: Wade JT, Struhl K, Busby SJ, Grainger DC.
Mol Microbiol
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.
Authors: Authors: Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE, Kuehn MS, Taylor CM, Neph S, Koch CM, Asthana S, Malhotra A, Adzhubei I, Greenbaum JA, Andrews RM, Flicek P, Boyle PJ, Cao H, Carter NP, Clelland GK, Davis S, Day N, Dhami P, Dillon SC, Dorschner MO, Fiegler H, Giresi PG, Goldy J, Hawrylycz M, Haydock A, Humbert R, James KD, Johnson BE, Johnson EM, Frum TT, Rosenzweig ER, Karnani N, Lee K, Lefebvre GC, Navas PA, Neri F, Parker SC, Sabo PJ, Sandstrom R, Shafer A, Vetrie D, Weaver M, Wilcox S, Yu M, Collins FS, Dekker J, Lieb JD, Tullius TD, Crawford GE, Sunyaev S, Noble WS, Dunham I, Denoeud F, Reymond A, Kapranov P, Rozowsky J, Zheng D, Castelo R, Frankish A, Harrow J, Ghosh S, Sandelin A, Hofacker IL, Baertsch R, Keefe D, Dike S, Cheng J, Hirsch HA, Sekinger EA, Lagarde J, Abril JF, Shahab A, Flamm C, Fried C, Hackermüller J, Hertel J, Lindemeyer M, Missal K, Tanzer A, Washietl S, Korbel J, Emanuelsson O, Pedersen JS, Holroyd N, Taylor R, Swarbreck D, Matthews N, Dickson MC, Thomas DJ, Weirauch MT, Gilbert J, Drenkow J, Bell I, Zhao X, Srinivasan KG, Sung WK, Ooi HS, Chiu KP, Foissac S, Alioto T, Brent M, Pachter L, Tress ML, Valencia A, Choo SW, Choo CY, Ucla C, Manzano C, Wyss C, Cheung E, Clark TG, Brown JB, Ganesh M, Patel S, Tammana H, Chrast J, Henrichsen CN, Kai C, Kawai J, Nagalakshmi U, Wu J, Lian Z, Lian J, Newburger P, Zhang X, Bickel P, Mattick JS, Carninci P, Hayashizaki Y, Weissman S, Hubbard T, Myers RM, Rogers J, Stadler PF, Lowe TM, Wei CL, Ruan Y, Struhl K, Gerstein M, Antonarakis SE, Fu Y, Green ED, Karaöz U, Siepel A, Taylor J, Liefer LA, Wetterstrand KA, Good PJ, Feingold EA, Guyer MS, Cooper GM, Asimenos G, Dewey CN, Hou M, Nikolaev S, Montoya-Burgos JI, Löytynoja A, Whelan S, Pardi F, Massingham T, Huang H, Zhang NR, Holmes I, Mullikin JC, Ureta-Vidal A, Paten B, Seringhaus M, Church D, Rosenbloom K, Kent WJ, Stone EA, Batzoglou S, Goldman N, Hardison RC, Haussler D, Miller W, Sidow A, Trinklein ND, Zhang ZD, Barrera L, Stuart R, King DC, Ameur A, Enroth S, Bieda MC, Kim J, Bhinge AA, Jiang N, Liu J, Yao F, Vega VB, Lee CW, Ng P, Shahab A, Yang A, Moqtaderi Z, Zhu Z, Xu X, Squazzo S, Oberley MJ, Inman D, Singer MA, Richmond TA, Munn KJ, Rada-Iglesias A, Wallerman O, Komorowski J, Fowler JC, Couttet P, Bruce AW, Dovey OM, Ellis PD, Langford CF, Nix DA, Euskirchen G, Hartman S, Urban AE, Kraus P, Van Calcar S, Heintzman N, Kim TH, Wang K, Qu C, Hon G, Luna R, Glass CK, Rosenfeld MG, Aldred SF, Cooper SJ, Halees A, Lin JM, Shulha HP, Zhang X, Xu M, Haidar JN, Yu Y, Ruan Y, Iyer VR, Green RD, Wadelius C, Farnham PJ, Ren B, Harte RA, Hinrichs AS, Trumbower H, Clawson H, Hillman-Jackson J, Zweig AS, Smith K, Thakkapallayil A, Barber G, Kuhn RM, Karolchik D, Armengol L, Bird CP, de Bakker PI, Kern AD, Lopez-Bigas N, Martin JD, Stranger BE, Woodroffe A, Davydov E, Dimas A, Eyras E, Hallgrímsdóttir IB, Huppert J, Zody MC, Abecasis GR, Estivill X, Bouffard GG, Guan X, Hansen NF, Idol JR, Maduro VV, Maskeri B, McDowell JC, Park M, Thomas PJ, Young AC, Blakesley RW, Muzny DM, Sodergren E, Wheeler DA, Worley KC, Jiang H, Weinstock GM, Gibbs RA, Graves T, Fulton R, Mardis ER, Wilson RK, Clamp M, Cuff J, Gnerre S, Jaffe DB, Chang JL, Lindblad-Toh K, Lander ES, Koriabine M, Nefedov M, Osoegawa K, Yoshinaga Y, Zhu B, de Jong PJ.
Nature
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Transcriptional noise and the fidelity of initiation by RNA polymerase II.
Authors: Authors: Struhl K.
Nat Struct Mol Biol
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[Histone H4 lysine 16 acetylation: from genome regulation to tumoral progression].
Authors: Authors: Miotto B, Struhl K.
Med Sci (Paris)
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The transition between transcriptional initiation and elongation in E. coli is highly variable and often rate limiting.
Authors: Authors: Reppas NB, Wade JT, Church GM, Struhl K.
Mol Cell
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Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells.
Authors: Authors: Yang A, Zhu Z, Kapranov P, McKeon F, Church GM, Gingeras TR, Struhl K.
Mol Cell
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Genome-wide location analysis of the stress-activated MAP kinase Hog1 in yeast.
Authors: Authors: Pascual-Ahuir A, Struhl K, Proft M.
Methods
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Rank-statistics based enrichment-site prediction algorithm developed for chromatin immunoprecipitation on chip experiments.
Authors: Authors: Ghosh S, Hirsch HA, Sekinger E, Struhl K, Gingeras TR.
BMC Bioinformatics
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