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

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 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.

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:

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. 16 847-852.
Hirsch, H.A., Iliopoulos, D., Tsichlis, P.N., and Struhl, K. (2009). Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 69 7507-7511.
Iliopoulos, D., Hirsch, H.A., and Struhl, K. (2009). An epigenetic switch involving NF-kB, Lin28, Let-7 microRNA, and IL6 links inflammation to cell transformation. Cell 139 693-706.
Miotto, B. and Struhl, K. (2010). HBO1 histone acetylase activity is essential for replication licensing and inhibited by Geminin. Mol. Cell. 37 57-66.
Hirsch, H.A., Iliopoulos, D., Joshi, A., Zhong, Y., Jaeger, S.A., Bulyk, M.L, Tsichlis, P.N. Liu, X.S., and Struhl, K. (2010). A transcriptional signature and common gene networks link cancer with lipid metabolism and diverse human diseases. Cancer Cell 17 348-361.

BBS webpage updated 5/11/2010