Kevin Struhl
Department of Biological Chemistry and Molecular Pharmacology
Harvard Medical School
Building C1, Room 315
240 Longwood Avenue
Boston, MA 02115
Tel: (617) 432-2104
Fax: (617) 432-2529
Email: kevin@hms.harvard.edu
Web Page: The Struhl Lab Page
10 postdoctoral students, 1 graduate student
The molecular mechanisms of transcriptional regulation are highly conserved among eukaryotes. 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. We combine genetic, molecular, genomic, and evolutionary approaches to address fundamental questions about transcriptional regulatory mechanisms 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) growth-regulated expression of ribosomal protein genes and activator-specific recruitment of TFIID, 2) novel aspects of signal transduction and gene regulation that occur during the response to osmotic stress, 3) how co-activators, chromatin-modifying complexes, and components of the basic transcription machinery are recruited to promoters in vivo under genetically and environmentally defined conditions, 4) mechanisms of global repression and gene silencing, 5) intrinsic and dynamic aspects of chromatin structure in vivo, 6) mechanisms of epigenetic inheritance of heterochromatic and euchromatic states, 7) distinguishing between biological function and biological noise using evolutionarily related yeast species and other approaches.
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) role of microRNAs at various stages of cellular transformation including potential connections to chromatin, 4) mechanistic analysis of the connection between lipid metabolism and transformation, 5) testing metformin as a potential anti-cancer drug.
References:
- Ng, H.H., Robert, F., Young, R.A., and Struhl, K. (2003). Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol. Cell 11 709-719.
- Cawley, S. et al. (2004). Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of non-coding RNAs. Cell 116 499-509.
- Katan-Khaykovich, Y. and Struhl, K. (2005). Heterochromatin formation involves changes in histone modifications over multiple cell generations. EMBO J. 24 2138-2149.
- Yang, A., Zhu, Z., Kapranov, P., McKeon, F., Church, G.M., Gingeras, T.R., and Struhl, K. (2006). Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells. Mol. Cell. 24 593-602.
- Miotto, B. and Struhl, K. (2008). HBO1 histone acetylase is a co-activator of the replication licensing factor Cdt1. Genes Dev. 22 2633-2638.
- Zhang, Y., Moqtaderi, Z., Rattner, B.P., Euskirchen, G., Snyder, M., Kadonaga, J.T., Liu, X.S., and Struhl, K. (2009). Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo. Nat. Struct Mol. Biol. in press.
BBS webpage updated 12/02/2009