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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
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
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-a Protein Turnover in the Presence of
Estrogen. J. Mol. Endocrinol., 40:
23-34, 2008.
Abstract |
Full Text |
PDF
Fowler, A. M., and Alarid, E. T.
Amping Up Estrogen Receptors in Breast Cancer. Breast
Cancer Res., 9:305, 2007.
Abstract
| Full Text | PDF
Jiang, X., Ellison, S. J., Alarid, E. T., and
Shapiro, D. J. Interplay between the Levels
of Estrogen and Estrogen Receptor Controls the Level of the
Granzyme Inhibitor, Proteinase Inhibitor 9 and
Susceptibility to Immune Surveillance by Natural Killer
Cells. Oncogene, 26: 4106-4114,
2007.
Abstract
Weinberg, A. L., Carter, D., Ahonen, M., Alarid, E.
T., Murdoch, F. E., and Fritsch, M. K. The
DNA Binding Domain of Estrogen Receptor a Is Required for High-Affinity Nuclear
Interaction Induced by Estradiol. Biochemistry,
46: 8933-8942, 2007.
Abstract
Alarid, E. T. Lives and Times of Nuclear
Receptors. Mol. Endocrinol., 20: 1972-1981,
2006.
Abstract | Full
Text | PDF
Fowler, A. M., Solodin, N. M., Valley, C. C., and
Alarid, E. T. Altered Target Gene Regulation
Controlled by Estrogen Receptor-a Concentration. Mol. Endocrinol.,
20: 291-301, 2006.
Abstract | Full
Text | PDF
Valley, C. C., Métivier, R., Solodin, N. M.,
Fowler, A. M., Mashek, M. T., Hill, L., and Alarid, E.
T. Differential Regulation of Estrogen-Inducible
Proteolysis and Transcription by the Estrogen Receptor
a N Terminus. Mol. Cell. Biol.,
25: 5417-5428, 2005.
Abstract
| Full
Text | PDF
Fowler, A. M., and Alarid, E. T. Nuclear
Receptor and Transcriptional Complex Cycles. Science STKE,
(262), tr11, 2004.
Abstract
Fowler, A. M., and Alarid, E. T. Dynamic
Control of Nuclear Receptor Transcription. Science STKE,
(256), pe51, 2004.
Abstract |
View Animation (caution: 7.5 MB)
Fowler, A. M., Solodin, N., Preisler-Mashek, M. T.,
Zhang, P., Lee, A. V., and Alarid, E. T. Increases
in Estrogen Receptor-a
Concentration in Breast Cancer Cells Promote Serine
118/104/106-independent AF-1 Transactivation and Growth in
the Absence of Estrogen. FASEB J., 18: 81-93,
2004.
Abstract
| Full
Text | PDF
Alarid, E. T., Preisler-Mashek, M. T., and Solodin,
N. M. Thyroid Hormone Is an Inhibitor of
Estrogen-Induced Degradation of Estrogen
Receptor-a Protein:
Estrogen-Dependent Proteolysis Is Not Essential for
Receptor Transactivation Function in the Pituitary.
Endocrinology, 144: 3469-3476, 2003.
Abstract | Full
Text | PDF
Preisler-Mashek, M. T., Solodin, N., Stark, B. L.,
Tyriver, M. K., and Alarid, E. T. Ligand-Specific
Regulation of Proteasome-Mediated Proteolysis of Estrogen
Receptor-a. Am. J. Physiol.
Endocrinol. Metab., 282: E891-E898, 2002.
Abstract |
Full Text | PDF
Alarid, E. T., Bakopoulos, N., and Solodin,
N. Proteasome-Mediated Proteolysis of Estrogen
Receptor: A Novel Component in Autologous Down-Regulation.
Mol. Endocrinol., 13: 1522-1534, 1999.
Abstract | Full
Text | PDF
Yusta, B., Alarid, E. T., Gordon, D. F., Ridgway,
E. C., and Mellon, P. L. The Thyrotropin
b-Subunit Gene Is Repressed by
Thyroid Hormone in a Novel Thyrotrope Cell Line, Mouse
TaT1 Cells. Endocrinology,
139: 4476-4482, 1998.
Abstract |
Full Text | PDF
Alarid, E. T., Windle, J. J., Whyte, D. B., and
Mellon, P.L. Immortalization of Pituitary Cells at
Discrete Stages of Development by Directed Oncogenesis in
Transgenic Mice. Development, 122: 3319-3329,
1996.
Abstract | PDF
Alarid, E. T., and Mellon, P. L.
Down-Regulation of the Gonadotropin-Releasing Hormone
Receptor Messenger Ribonucleic Acid by Activation of
Adenylyl Cyclase in aT3-1
Pituitary Gonadotrope Cells. Endocrinology, 136:
1361-1366, 1995.
Abstract