Dr. Davidson received her MD in 1979 from Harvard Medical School in Boston, MA, and completed internal medicine training at the Hospital of the University of Pennsylvania and Johns Hopkins. Dr. Davidson was a Medical Staff Fellow and guest worker at the National Cancer Institute in Bethesda from 1982-86 where she developed a major interest in the breast cancer field. She joined the faculty at the Johns Hopkins University School of Medicine in 1986 as an Assistant Professor in Oncology. Today, Dr. Davidson is a Professor of Oncology and holds the Breast Cancer Research Chair in Oncology. Dr. Davidson also serves as Director of the Breast Cancer Research Program.

Trained as a medical oncologist and scientist, Dr. Davidson has devoted her career to breast cancer research, in both the clinical and laboratory setting. Her clinical research has focused on the value of combination therapy with chemotherapy and hormonal therapy for young women with breast cancer. One of her major laboratory interests has been the definition of the biochemical pathways by which breast cancer cells die, in the hope that new targets for anti-breast cancer therapy can be identified as well as epigenetic regulation of gene expression.

DNA Methylation and Steroid Receptor Regulation

Numerous experimental and clinical studies have established that estrogen plays a major role in the initiation and progression of breast cancer. About two-thirds of breast cancers express the estrogen receptor, a transcription factor of the nuclear hormone receptor superfamily, and their growth is often stimulated by estrogen. The remainder lack detectable estrogen receptor protein and rarely respond to such treatment. Thus regulation of the estrogen receptor is a critical determinant of breast cancer growth. Our laboratory has demonstrated a potential role for abnormal DNA methylation in transcriptional inactivation of the estrogen receptor gene. Estrogen receptor-negative human breast cancer cells growing in culture lack estrogen receptor mRNA, have a higher capacity to methylate DNA, and display extensive methylation of the CpG island in the 5' promoter region of the estrogen receptor gene which correlates with silencing of expression. Treatment with demethylating agents leads to demethylation and subsequent expression of functional estrogen receptor protein, supporting a functional role for this aberrant pattern of methylation. Current work is focused on the role of DNA methylation and histone acetylation in ER gene regulation. In addition, a separate project explores the possible therapeutic exploitation of the polyamine pathway.

DNA Methylation and Steroid Receptor Regulation

Yang, X., Ferguson, A.T., Nass, S.J., Phillips, D.L., Butash, K.A., Wang, S.M., Herman, J.G., and Davidson, N.E. Transcriptional activation of estrogen receptor a in human brease cancer cells by histone deacetylase inhibition. Cancer Res., in press.

Nass, S.J., Herman, J.G., Gabrielson, E., Iversen, P.W., Davidson, N.E., and Graff, J.R. Aberrant methylation of the estrogen receptor and E-cadherin 5¢ CpG islands increases with malignant progression in human breast cancer. Cancer Res., 60, 4346-4348, 2000.

Nass, S.J., Ferguson, A.T., El-Ashry, D., Nelson, W.G., and Davidson, N.E., Expression of DNA methyltransferase (DMT) and the cell cycle in human breast cancer cells. Oncogene, 18, 7453-7461, 1999.

Ferguson, A.T., Lapidus, R.G., and Davidson, N.E., Demethylation of the progesterone receptor CpG island is not required for progesterone receptor gene expression. Oncogene, 17, 577, 1998.