Dale Leitman
Adjunct Professor
Research Description
With the increasing longevity of the population approximately one-third of a woman’s life occurs during menopause. During menopause the levels of estrogens in body drop to very low levels. This can lead to a variety of conditions that occur shortly after menopause, such as hot flashes, mood swings and genital atrophy. Long-term loss of estrogens can be associated with chronic conditions, such as osteoporosis, cardiovascular disease, obesity and Alzheimer’s disease. Menopausal women have been prescribed estrogens for decades to prevent or treat these conditions. However, recent clinical trials have found that estrogens used in current hormone therapy regimens cause adverse effects that exceed the benefits. This has created an urgent need to discover safer alternative treatments for conditions associated with menopause. The goals of our research are to determine the molecular mechanisms whereby estrogens produce distinct biological and clinical effects and to discover safer and more selective estrogens to prevent or treat hot flashes, breast cancer, obesity, osteoporosis and cardiovascular disease. Additional information can be found at our lab web site.
For more information, please visit Leitman Lab.
Publications
Most Recent Publications
1. An, J., Ribeiro, R.C.J., Webb, P. Gustafsson, J. A., Lomri, N., Kushner, P. J., Baxter, J. D. and D. C. Leitman. Estradiol repression of tumor necrosis factor-α transcription requires estrogen receptor function-2 and is enhanced by coactivators. Proceedings National Academy of Sciences USA 96:15161-15166, 1999.
2. An, J., Tzagarakis-Foster, C. Scharschmidt, T. C., Lomri, N. and D. C. Leitman. Estrogen receptor β selective transcriptional activity and coregulator recruitment by phytoestrogens. Journal of Biological Chemistry 276:17808-17814, 2001.
3. Tzagarakis-Foster, C., Geleziunas, R., Lomri, A., An, J. and D. C. Leitman. Estradiol represses human T-cell leukemia virus type I tax activation of tumor necrosis factor-α gene transcription. Journal of Biological Chemistry 277:44772-44777, 2002.
4. Paruthiyil, S., Parmar, H., Kerekatte, V. Cunha, G. R., Firestone, G. L. and D. C. Leitman. Estrogen receptor β inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest. Cancer Research, 64:423-428, 2004.
5. Tee, M. K., Rogatsky, I., Tzagarakis-Foster, C., Cvoro, A., An, J., Christy, R. J., Yamamoto, K. R. and D. C. Leitman. Estradiol and selective estrogen receptor modulators differentially regulate target genes by estrogen receptor α and β Molecular Biology of the Cell, 15:1262-1272, 2004.
6. Cvoro, A., Tzagarakis-Foster, C., Tatomer, D., Paruthiyil, S. Fox, M. and D. C. Leitman. Distinct roles of unliganded and liganded estrogen receptors in transcriptional repression. Molecular Cell 21, 555–564, 2006.
7. Cvoro, A., Paruthiyil, S., Jones, J., Tzagarakis-Foster, C., Clegg, N. J., Tatomer, D., Medina, R. T. Tagliaferri, M., Schaufele, F., Scanlan, T. S., Diamond, M. I. and D. C. Leitman. Selective Activation of Estrogen Receptor β Transcriptional Pathways by an Herbal Extract Used to Treat Hot Flashes. Endocrinology 148:538-547, 2007.
8. Levy, N. Zhao, X., Tang, H., Jaffe, R. B., Speed, T. P. and D. C. Leitman. Multiple transcription factor elements collaborate with ERα to mediate transcriptional activation by estradiol and SERMs. Endocrinology 148:3449-3558, 2007.
9. Levy, N. Tatomer, D., Herber, C. B., Zhao, X., Tang, H., Sargeant, T, Ball, L. J., Summers, J., Speed, T. P. and Dale C. Leitman. Estradiol and selective estrogen receptor modulators differentially regulate native estrogen receptor regulatory elements with ERα and ERβ. Molecular Endocrinology, 22:287-303, 2008.
10. Cvoro A, Tatomer, D., Tee M-K., Zogric, T. Harris H. A., and D. C. Leitman. Selective Estrogen Receptor-β Agonists Repress Transcription of Proinflammatory Genes. Journal of Immunology, 180: 630–636, 2008.
11. Mersereau, J. E., Levy, N., Staub, R. E., Baggett, S., Zogric, T., Chow, S., Ricke, W. A., Tagliaferri, M., Cohen, I., Bjeldanes L. F. and D. C. Leitman. Liquiritigenin is a Plant-derived Highly Selective Estrogen Receptor β Agonist. Molecular and Cellular Endocrinology, 283:49-57 2008.
12. Ball, L. J., Levy, N., Zhao, X., Griffin, C, Tagliaferri, M., Cohen, I., Ricke, W. A, Speed, T. P., Firestone, G. L. and D. C. Leitman. Cell type- and estrogen receptor-subtype specific regulation of selective estrogen receptor modulator regulatory elements. In Press, Molecular and Cellular Endocrinology.
