Dean P. Edwards, Ph.D.
Departments of Molecular and Cellular Biology and Pathology and Immunology
Associate Director for Research Infrastructure
Dan L. Duncan Cancer Center
Executive Director, Advanced Technology Cores at BCM
Ph.D.: Medical College of Georgia, Augusta
Postdoctoral training: University of Texas Health Sciences Center, San Antonio
Steroid Receptors in Mammary Gland Development and Breast Cancer
A main interest of the Edwards laboratory is the role of progesterone and progesterone receptor (PR) in the normal breast and breast cancer. Progesterone is a major regulator of normal breast development and it has different effects at different stages of development. Progesterone stimulates proliferation of breast epithelial cells during puberty and at early stages of pregnancy while it inhibits proliferation and induces programs of differentiation at mid-to-late pregnancy that results in development of lobuloalveolar structures required for milk production. Progesterone and its receptor have dual roles in breast cancer. Progesterone is a risk factor for early stages of breast cancer development yet at later stages of breast cancer, PR is a favorable prognostic factor. Loss of PR during tumor progression is associated with a less differentiated more invasive phenotype. The Edwards lab is interested in how alterations in progesterone/PR signaling pathways contribute to the biology and progression of breast cancer and how this information may be exploited for identification of novel diagnostic or therapeutic targets. They have developed model systems to study how dysregulation of proliferative response to progesterone contributes to early stages of pre-neoplastic progression. These studies include changes between normal and cancer cells in paracrine and oncogenic signaling pathways, such as the c-Src tyrosine kinases, regulated by PR. Using in vitro models of invasive breast cancer, the Edwards lab has shown that PR has tumor suppressor activity through inhibiting epithelial-to-mesenchymal transition (EMT) that is an essential step in invasion and metastasis. These data provide a mechanism for PR as a favorable marker in primary tumors. Ongoing studies seek to define the effector pathways responsible for the tumor suppressor activity of PR with the long-term goal of developing drugs that could reactivate these pathways as a potential therapeutic target for the more aggressive PR negative breast cancer. The Edwards lab also examines the structure function properties of PR as a nuclear transcription factor and the molecular mechanisms by which PR regulates gene transcription. Biophysical and high resolution NMR and x-ray crystallography studies are being conducted to understand how conformational changes in receptor structure regulate its interaction with DNA and co-regulatory proteins.
Another research area is the development of technologies to identify alterations in the global patterns of proteins (proteome) and metabolites (metabolome) in cancer. Dr. Edwards is Principle Investigator of a CPRIT (Cancer Prevention and Research Institute of Texas) grant to build a Cancer Metabolomics and Proteomics Core Facility. This new Facility provides high-end instrumentation and technology platforms for multiple cancer investigators at Baylor College of Medicine to use for identification of changes in the proteome or metabolome in all cancer cell types of interest. This CPRIT Core Facility is a major effort of the Cancer Center to identify new therapeutic targets and develop novel drugs for personalized treatment of cancer.
Baylor College of Medicine
One Baylor Plaza, ABBR Room R505
Houston, TX 77030
- Obr A and Edwards DP. (2012). The biology of progesterone and progesterone receptor in the normal mammary gland and in breast cancer. Mol Cell Endocrinol 357:4-17. PMCID: PMC3318965.
- Hill KK, Roemer SC, Churchill MAE and Edwards DP. (2011). Structural and functional analysis of domains of progesterone receptor. Mol Cell Endocrinol 348:418-429. PMID: 21803119. NIHMS313758.
- Buser AC, Obr AE, Kabotyanski EB, Grimm SL, Rosen JM and Edwards DP. (2011). Progesterone receptor directly inhibits -casein gene transcription in mammary epithelial cells through promoting promoter and enhancer repressive chromatin modifications. Mol Endocrinol 25:955-968. PMCID: PMC3386529.
- Wardell SE, Narayanan R, Weigel NL and Edwards DP. (2010). Partial agonist activity of the progesterone receptor antagonist RU486 mediated by an amino-terminal domain coactivator and phosphorylation of serine 400. Mol Endocrinol 24:335-345. PMCID: PMC2817605.
- Hill KK, Roemer SC, Jones DNM, Churchill MEA and Edwards DP. (2009). A progesterone receptor co-activator (JDP2) mediates activity through interaction with residues in the carboxyl terminal extension of the DNA binding domain. J Biol Chem 284:24415-24424. PMCID: PMC2782034.
- Roemer SC, Adelman J, Churchill MEA and Edwards DP. (2008). Mechanism of high-mobility group protein B enhancement of progesterone receptor sequence-specific DNA binding. Nucleic Acids Res 36:3655-3666. PMCID: PMC2441811.
- Boonyaratanakornkit V, McGowan E, Sherman L, Mancini MA, Cheskis BJ and Edwards, DP. (2007). The role of extra-nuclear signaling actions of progesterone receptor in mediating progesterone regulation of gene expression and the cell cycle. Mol Endocrinol 21:359-375.
- Buser AD, Gass Handel EK, Wyszomierski SL, Doppler W, Leonhardt SA, Schaack J, Rosen JM, Watkin H, Anderson SM and Edwards DP. (2007). Progesterone receptor repression of prolactin/Stat5-mediated transcription of the -casein gene in mammary epithelial cells. Mol Endocrinol 21:106-125.
- Roemer SC, Donham DC, Sherman L, Pon VH, Edwards DP and Churchill MEA. (2006). Structure of the progesterone receptor DNA Complex: Novel interactions required for binding to half-site response elements. Mol Endocrinol 20:3042-3052.
- Boonyaratanakornkit V, Porter M, Ribon V, Sherman L, Anderson SA, Miller WT and Edwards DP. (2001). Progesterone receptor contains a proline rich sequence in the amino terminus that directly interacts with SH3 domains and activates Src family tyrosine kinases. Mol Cell 8:269-280.