Elaine T. Alarid, Ph.D.
Associate Professor of Oncology
B.A., 1985, Genetics, University of
California-Berkeley
Ph.D., 1991, Physiology, University of
California-Berkeley
Postdoctoral research: UC-San Francisco and UC-San Diego
Office: 6151 Wisconsin Institutes for Medical Research (WIMR)
Telephone: Office - (608) 265-9319;
Lab - (608) 265-9318
Email: alarid@oncology.wisc.edu
Research Interests: Molecular mechanisms of steroid hormone action
Research Description: 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.
Figure 1: Model of a "Transcriptional
Clock"
Selected publications
Rajbhandari, P., Finn, G., Solodin, N. M., Singarapu, K. K., Sahu, S. C., Markley, J. L., Kadunc, K. J., Ellison-Zelski, S. J., Kariagina, A., Haslam, S. Z., Lu, K. P., and Alarid, E. T. Regulation of Estrogen Receptor α N-Terminus Conformation and Function by Peptidyl Prolyl Isomerase Pin1. Mol. Cell. Biol., 32: 445-457, 2012.
Abstract
Berry, S. M., Alarid, E. T., and Beebe, D. J. One-Step Purification of Nucleic Acid for Gene Expression Analysis via Immiscible Filtration Assisted by Surface Tension (IFAST). Lab Chip, 11: 1747-1753, 2011.
Abstract
Berry, S. M., Strotman, L. N., Kueck, J. D., Alarid, E. T., and Beebe, D. J. Purification of Cell Subpopulations via Immiscible Filtration Assisted by Surface Tension (IFAST). Biomed. Microdevices, 13: 1033-1042, 2011.
Abstract
Welsh, A. W., Moeder, C. B., Kumar, S., Gershkovich, P., Alarid, E. T., Harigopal, M., Haffty, B. G., and Rimm, D. L. 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, 2011.
Abstract
Ellison-Zelski, S. J., and Alarid, E. T. Maximum Growth and Survival of Estrogen Receptor-Alpha Positive Breast Cancer Cells Requires the Sin3A Transcriptional Repressor. Mol. Cancer, 9:263, 2010.
Abstract | Full Text | PDF
Powers, G. L., Ellison-Zelski, S. J., Casa, A. J., Lee, A. V., and Alarid, E. T. Proteasome Inhibition Represses ERα Gene Expression in ER + Cells: A New Link between Proteasome Activity and Estrogen Signaling in Breast Cancer. Oncogene, 29: 1509-1518, 2010.
Abstract
Ellison-Zelski, S. J., Solodin, N. M., and Alarid, E. T. Repression of ESR1 through Actions of Estrogen Receptor Alpha and Sin3A at the Proximal Promoter. Mol. Cell. Biol., 29: 4949-4958, 2009.
Abstract | Full Text | PDF
Regehr, K. J., Domenech, M., Koepsel, J. T., Carver, K. C., Ellison-Zelski, S. J., Murphy, W. L., Schuler, L. A., Alarid, E. T., and Beebe, D. J. Biological Implications of Polydimethylsiloxane-Based Microfluidic Cell Culture. Lab Chip, 9: 2132-2139, 2009.
Abstract
Valley, C. C., Solodin, N. M., Powers, G. L.,
Ellison, S. J., and Alarid, E. T. Temporal
Variation in Estrogen Receptor-α Protein Turnover in the Presence of
Estrogen. J. Mol. Endocrinol., 40:
23-34, 2008.
Abstract |
Full Text |
PDF
Weinberg, A. L., Carter, D., Ahonen, M., Alarid, E. T., Murdoch, F. E., and Fritsch, M. K. The DNA Binding Domain of Estrogen Receptor α Is Required for High-Affinity Nuclear Interaction Induced by Estradiol. Biochemistry, 46: 8933-8942, 2007.
Abstract | Full Text | PDF