Laboratory

Research

We have applied genomic, computational, and molecular approaches towards understanding basic mechanisms of nuclear receptor biology and their impact on human diseases. Our research has focused on estrogen receptors (ERs)and their role in breast cancer, and we have utilized microarrays, binding site modeling, and chromatin immunoprecipitation (ChIP) to study transcriptional regulatory mechanisms and gene expression profiles associated with disease outcomes in patient samples. Using the experimental approaches and tools developed and refined in our studies of estrogen receptors, we look to expand our efforts towards characterizing other nuclear receptors and their roles in biological and pathogenic processes.

Collaborators

Relevant Publications

Bajic, V.B., Tan, S.L., Chong, A., Tang, S., Strom, A., Gustafsson, J.- Å., Lin, C.-Y., and Liu, E.T. Dragon ERE Finder ver. 2.0: A tool for accurate detection of estrogen response elements in vertebrate genomes. Nucleic Acid Res 2003; 31(13):3605-07.

Vega, V.B., Bangarusamy, D.K., Miller, L.D., Liu, E.T., and Lin, C.-Y. BEARR: Batch extraction and analysis of cis-regulatory regions. Nucleid Acid Res. 2004; 32 Web Server Issue: W257-60.

*Lin, C.-Y., Strom, A., Vega, V.B., Kong, S.L., Thomsen J.S., Yeo, A.L., Doray, B., Chan, W.C., Bangarusamy, D.K., Tang, S., Chong, A., Bajic, V.B., Ramasamy, A., Vergara, L., Miller, L.D., Gustafsson, J.- Å., and Liu, E.T. Discovery of estrogen receptor a target genes and response elements in breast tumor cells. Genome Biology 2004; 5 (9):R66. *Designated as a Highly Accessed article by BioMed Central.

Reid, G., Metivier, R., Lin, C.-Y., Ibberson, D., Denger, S., Brand, H., Liu, E.T., and Gannon, F. Multiple mechanisms induce transcriptional silencing of a subset of genes, including oestrogen receptor alpha, in response to deacetylase inhibition by valproic acid and trichostatin A. Oncogene 2005; 24 (31):4894-907.

Hall, P., Ploner, A., Bjohle, J., Huang, F., Lin, C.-Y., Liu, E.T., Miller, L.D., Pawitan, Y., Shaw, P., Skoog, L., Smeds, J., Wedren, S, Ohd, J., and Bergh, J. Postmenopausal hormone replacement therapy represses gene expression in human breast cancer. BMC Med. 2006; 4:16.

Frasor, J., Chang, E., Komm, B., Lin, C.-Y., Liu, E.T., Miller, L.D., Bergh, J., Smeds, J., and Katzenellenbogen, B.S. Gene expression preferentially regulated by Tamoxifen in breast cancer cells and correlations with clinical response. Cancer Res. 2006; Jul 15; 66(14):7334-40.

Su, X., Lin, C.-Y.; O'Shea, S. J., Teh, H. F., Peh, W. Y. X., and Thomsen, J. S. Combinational Application of Surface Plasmon Resonance Spectroscopy and Quartz Crystal Microbalance for Studying Nuclear Hormone Receptor-Response Element Interactions. Anal. Chem. 2006; Aug 1;78(15):5552-8.

*Vega, V.B., *Lin, C.-Y., Lai, K.S., Kong, S.L., Xie, M., Su, X., The, H.F., Thomsen, J.S., Yeo, A.L., Sung, W.K., Bourque, G., Liu, E.T. Multi-platform genome-wide identification and modeling of functional human estrogen receptor binding sites. Genome Biol. 2006;7(9):R82. *Shared first authorship and designated as a Highly Accessed article by BioMed Central.

Nilsson, M, Stulnig, T.M., Lin C.-Y., Yeo, A.L., Nowotny, P., Liu, E.T., and Steffensen, K.R. Liver X receptors regulate adrenal steroidogenesis and hypothalamic-pituitary-adrenal feedback. Mol. Endo., 2007; 21(1):126-137.

*Lin, C.-Y., Strom, A., Kong, S.L., Kietz, S., Thomsen, J.S., Tee, J.B.S., Vega, V.B., Miller, L.D., Johanna Smeds, Jonas Bergh, Gustafsson, J.- Å., and Liu, E.T. Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer. Breast Cancer Res., 2007; 9(2):R25. *Designated as a Highly Accessed article by BioMed Central.

*Lin, C.-Y., *Vega, V.B., Thomsen, J.S., Zhang, T., Kong, S.L., Xie, M., Chiu, K.P., Lipovich, L., Barnett, D.H., Stossi, F., Yeo, A., George, J., Kuznetsov, V.A., Lee, Y.K., Charn, T.H., Palanisamy, N., Cheung, E., Katzenellenbogen, B.S., Miller, L.D., Ruan, Y., Bourque, G., Wei, C.L., and Liu, E.T. Whole-genome Cartography of Estrogen Receptor a Binding Sites. PLOS Genetics 2007, 3(6):e87. *Shared first authorship.

Denger, S., Bahr-Ivacevic, T., Brand, H., Reid, G., Blake, J., Seifert, M., Lin, C.-Y., May, K., Benes, V., Liu, E.T., and Gannon, F. Transcriptome profiling of estrogen-regulated genes in human primary osteoblasts reveals an osteoblast specific regulation of the IGFBP4 gene. Mol. Endo. 2008, 22(2):361-79.

Barnett, D.H., Sheng, S., Charn, T.-H., Waheed, A, Sly, W.S., Lin, C.-Y., Liu, E.T., and Katzenellenbogen, B.S. Estrogen Receptor Regulation of the Carbonic Anhydrase XII (CA12) Gene Through a Distal Enhancer. Cancer Res. 2008, 68(9):3505-15.

Müller, P., Merrell, K.W., Crofts, J.D., Ronnlund, C., Lin, C.-Y., Gustafsson, J.-Å., and Ström, A. Estrogen-dependent downregulation of HES-1 gene expression in breast cancer cells is mediated via a 3 distal element. J. Endo. 2009, 200(3):311-19.

Müller, P.,Crofts, J.D., Newman, B.S., Bridgewater, L.C., Lin, C.-Y., Gustafsson, J.-Å., and Ström, A. SOX9 mediates the retinoic acid-induced HES-1 gene expression in human breast cancer cells. Breast Can. Res. Treat. 2009, Mar. 26, [Epub ahead of print].

Frasor, J., Weaver, A., Pradhan, M., Dai, Y., Miller, L.D., Lin, C.-Y., Stanculescu, A. and Positive Crosstalk between Estrogen Receptor and NF-kB in Breast Cancer. Cancer Res. 2009, 69(23):8918-25.