uhansen@bu.edu

Cell Signaling and Gene Regulation Cancer Biology

Professor of Biology
Ph.D., Harvard University, 1980

Molecular biology, transcriptional control, chromatin, estrogen, cardiovascular disease, cell growth and cycle

My laboratory studies how regulating gene expression in mammalian cells controls biological processes such as cell growth and responses to hormones. Our interests span how estrogen protects blood vessels from injury and cardiovascular disease, how regulation of transcription factors activates or represses expression of critical genes, and how signal transduction pathways target transcription machinery. We also use bioinformatics to understand the transcriptional regulatory networks involved in the biological processes being studied.

One major area of focus is how the transcription factor LSF controls cell growth and cell cycle progression into DNA replication, and also may inhibit apoptosis. A critical gene targeted by LSF is thymidylate synthase, an essential enzyme for cell growth that many chemotherapeutic drugs specifically inhibit. LSF is a ubiquitous, specific DNA-binding protein with an unusual structure; it interacts with directly repeated DNA half sites as an obligate protein tetramer. LSF activity is regulated by phosphorylation at a number of sites, in response to multiple signaling pathways.   Its activity is tightly regulated during cell growth stimulation and cell cycle progression.

A second major focus relates to how estrogen is protective against cardiovascular disease. Cells respond to estrogen through estrogen receptors alpha and beta, which recognize specific sequences in DNA and regulate transcription of the associated genes. We are identifying transcriptional targets of both estrogen receptors in vascular endothelial and vascular smooth muscle cells, and determining which are critical to control of cell proliferation and migration of the vascular cell types. These studies aim to establish a benchmark for cellular genes that may be targeted for pharmaceutical intervention in treatment or prevention of cardiovascular disease.

Finally, we consider the interplay between transcription machinery (such as estrogen receptor) and the chromatin with which it interacts. We have investigated a small structural abundant chromosomal protein, HMGN1, which can alter overall accessibility of genes to the transcription machinery by determining the ability of the chromatin to be compacted into a higher order structure.   HMGN1 also specifically binds estrogen receptor a and modulates estrogen-dependent transcription of some of its target genes.

Zhu N, Hansen U. (2007) HMGN1 modulates estrogen-mediated transcriptional activation through interactions with specific DNA-binding transcription factors. Mol Cell Biol, 27:8859-8873.

O'Lone R*, Knorr K*, Jaffe IZ, Schaffer ME, Martini PGV, Karas RH, Bienkowska J, Mendelsohn ME, Hansen U. (2007) Estrogen receptors alpha and beta mediate distinct pathways of vascular gene expression, including genes involved in mitochondrial electron transport and generation of reactive oxygen species. Mol Endocrinol. 21:1281-1296.

Ylisastigui L, Kaur R, Johnson H, Volker J, He G, Hansen U, Margolis D. (2005) Mitogen-activated protein kinases regulate LSF occupancy at the HIV-1 promoter. J Virol. 79:5952-5962.

Haverty PM, Weng Z, Hansen U. (2005) Transcriptional regulatory networks activated by PI3K and ERK transduced growth signals in human glioblastoma cells. J Comput Sci & Technol. 20:439-445.

Frith MC, Fu Y, Yu L, Chen J-F, Hansen U, Weng Z. (2004) Detection of functional DNA motifs via statistical overrepresentation. Nucleic Acids Res. 32:1372-1381.

O'Lone R, Frith MC, Karlsson EK, Hansen U. (2004) Genomic targets of nuclear estrogen receptors. Mol Endocrinol. 18:1859-1875.

Veljkovic J, Hansen U. (2004) Lineage-specific and ubiquitous biological roles of the mammalian transcription factor LSF. Gene 343:23-40.

Frith MC, Hansen U, Spouge, JL, Weng Z. (2004) Finding functional sequence elements by multiple local alignment. Nucleic Acids Res. 32:189-200.

Haverty PM, Hansen U, Weng Z. (2004) Computational inference of transcriptional regulatory networks from expression profiling and transcription factor binding data. Nucleic Acids Res. 32:179-188.

Haverty PM, Hsiao L-L, Gullans SR, Hansen U, Weng Z. (2004) Limited agreement among three global gene expression methods highlights the requirement for non-global validation. Bioinformatics 20:3431-3441.

Venkatesan K, McManus HR, Mello CC, Smith TF, Hansen U. 2003. Functional conservation between members of an ancient duplicated transcription factor family, LSF/Grainyhead. Nucleic Acids Res., 31:4304-4316.

Pagon Z, Volker J, Cooper GM, Hansen U. 2003. Mammalian transcription factor LSF is a target of ERK signaling. J Cell Biochem., 89:733-746.

Drouin EE, Schrader CE, Stavnezer J, Hansen U. 2002. The ubiquitously expressed DNA-binding protein LSF binds immunoglobulin switch regions and represses class switching to IgA. J Immunol., 168:2847-2856.

Frith MC, Spouge JL, Hansen U, Weng Z. 2002. Statistical significance of clusters of motifs represented by position specific scoring matrices in nucleotide sequences. Nucleic Acids Res., 30:3214-3224.

Bruni P, Minopoli G, Brancaccio T, Napolitano M, Faraonio R, Zambrano N, Hansen U, Russo T. 2002. Fe65, a ligand of the Alzheimer's b-amyloid precursor protein, blocks cell cycle progression by down-regulating thymidylate synthase expression. J Biol Chem., 277:35481-35488.

Frith MC, Hansen U, Weng Z. 2001. Detection of cis-element clusters in higher eukaryotic DNA. Bioinformatics; 17:878-889.

Sewack GF, Ellis TW, Hansen U. 2001. Binding of TATA binding protein to a naturally positioned nucleosome is facilitated by histone acetylation. Mol Cell Biol.; 21:1404-1415.

Coull JJ, Romerio F, Sun J-M, Volker JL, Galvin KM, Davie JR, Shi Y, Hansen U, Margolis DM. 2000. The human factors YY1 and LSF repress the human immunodeficiency virus type-1 long terminal repeat via recruitment of histone deacetylase 1. J Virol.; 74:6790-6799.

Powell CMH, Rudge TL, Zhu Q, Johnson LF, Hansen U. 2000. Inhibition of the mammalian transcription factor LSF induces S phase-dependent apoptosis by downregulating thymidylate synthase expression. EMBO J.; 19:4665-4675.

Hansen U. 1999. Transcriptional and structural analyses of isolated SV40 chromatin. in "Methods in Molecular Biology: Chromatin Protocols", Humana Press, Totowa, N.J.; vol. 119, pp. 261-290.

Shirra MK, Hansen U. 1998. LSF and NTF-1 share a conserved DNA-recognition motif yet require different oligomerization states to form a stable protein-DNA complex. J Biol Chem 273:19260-19268.

Ding, H.-F., M. Bustin, and U. Hansen. 1997. Alleviation of histone H1- mediated transcriptional repression and chromatin compaction by the acidic activation region in chromosomal protein HMG-14. Molecular and Cellular Biology 17:5843-5855.

Sewack, G.F. and U. Hansen. 1997. Nucleosome positioning and cell type specific chromatin alterations on the human estrogen-responsive pS2 promoter. Journal of Biological Chemistry 272:31118-31129.

Volker, J.L., L.E. Rameh, Q. Zhu, J. DeCaprio, and U. Hansen. 1997. Mitogenic stimulation of resting T cells causes rapid phosphorylation of the transcription factor LSF and increased DNA-binding activity. Genes and Development 11:1435-1446.

Questions and comments are always welcome.
Copyright © 1996, The Trustees of Boston University
This document was last modified on Dec. 19, 2007.