Faculty: Elaine T. Alarid, Ph.D.
|Dept:||Professor of Oncology|
|Contact:|| 6151 WIMR |
Figure 1. Model of a "transcriptional clock."
The focus of our research is on understanding the molecular mechanisms governing the activity of estrogen receptor (ER), a member of the nuclear receptor transcription factor family that is critical in normal reproduction and is implicated in the pathogenesis of breast cancer. ER is an intracellular receptor that when activated by estrogen and other estrogen-like compounds, binds directly to DNA and activates or represses gene transcription. It serves as an important model for the understanding of basic mechanisms of transcription, as well as the regulatory pathways that control the cellular responses to steroid hormones.
Currently, we are pursuing projects that address the role of post-translational regulation in the control of ERa protein activity, with emphasis on proteasome-mediated proteolysis. Experiments are aimed at better defining the signals that target ER for destruction and understanding how protein stability affects ERa transcriptional function. In trying to elucidate the link between protein stability and transactivation, our research has identified novel regulatory and activation mechanisms for ERa and is placed into an emerging model of a “transcriptional clock” (Figure 1) that explores the dynamics and specificity of macromolecular complexes governing gene expression.
Honors & Awards
- 2013 Vilas Associate
- University of Wisconsin Institute for Clinical and Translational Research
- University of Wisconsin Comprehensive Cancer Center
- Minority Action Committee of the Endocrine Society member
- Lang, J. D., Berry, S. M., Powers, G. L., Beebe, D. J., andAlarid, E. T. Hormonally Responsive Breast Cancer Cells in a Microfluidic Co-Culture Model as a Sensor of Microenvironmental Activity. Integr. Biol. (Camb.),5(5):807-816, 2013.
- Rajbhandari, P., Schalper, K. A., Solodin, N. M., Ellison-Zelski, S. J., Lu, K. P., Rimm, D. L., and Alarid, E. T. Pin1 Modulates ERα Levels in Breast Cancer through Inhibition of Phosphorylation-Dependent Ubiquitination and Degradation. Oncogene, in press, 2013 [Epub ahead of print Apr 1 2013].
- Rajbhandari P, Finn G, Solodin NM, Singarapu KK, Sahu SC, Markley JL, Kadunc KJ, Ellison-Zelski SJ, Kariagina A, Haslam SZ, Lu KP, and Alarid ET (2012) Regulation of Estrogen Receptor ± N-Terminus Conformation and Function by Peptidyl Prolyl Isomerase Pin1. Mol Cell Biol. 32:445-457. PMCID: PMC3255769
- Berry SM, Strotman LN, Kueck JD, Alarid ET, and Beebe DJ (2011). Purification of cell subpopulations via immiscible filtration assisted by surface tension (IFAST). Biomed Microdevices. 13:1033-1042. PMCID: PMC3314424
- Welsh AW, Moeder CB, Kumar S, Gershkovich P, Alarid ET, Harigopal M, Haffty BG, and Rimm DL (2011). Standardization of estrogen receptor measurement in breast cancer suggests false-negative results are a function of threshold intensity rather than percentage of positive cells. J Clin Oncol. 29:2978-2984. PMID: 21709197
- Berry SM, Alarid ET, and Beebe DJ (2011). One-step purification of nucleic acid for gene expression analysis via Immiscible Filtration Assisted by Surface Tension (IFAST). Lab Chip. 11:1747-1753. PMCID: PMC3244820
- Ellison-Zelski SJ, and Alarid ET (2010) Maximum growth and survival of estrogen receptor-alpha positive breast cancer cells requires the Sin3A transcriptional repressor. Mol Cancer. 9:263. PMCID: PMC2956731
- Powers GL, Ellison-Zelski SJ, Casa AJ, Lee AV, and Alarid ET (2010). Proteasome inhibition represses ERalpha gene expression in ER+ cells: a new link between proteasome activity and estrogen signaling in breast cancer. Oncogene. 29:1509-18. PMID: 19946334
- Ellison-Zelski SJ, Solodin NM, and Alarid ET (2009). Repression of ESR1 through actions of estrogen receptor alpha and Sin3A at the proximal promoter. Mol Cell Biol 29:4949-4945. PMID 19620290
- Regehr KJ, Domenech M, Koepsel JT, Carver KC, Ellison-Zelski SJ, Murphy WL, Schuler LA, Alarid ET, and Beebe DJ (2009). Biological implications of polydimethylsiloxane-based microfluidic cell culture. Lab Chip. 9:2132-2139.
- Valley CC, Solodin N, Powers G, and Alarid ET. (2008) Temporal variation in estrogen receptor-Éø protein turnover in the presence of estrogen. J Mol Endocrinol. 40:23-34.