Email

deane@bcm.edu

Positions

Professor

Mol & Cell Biology and Pathology & Immunology
Baylor College of Medicine
Houston, TX US

Executive Director, Advanced Technology Cores

Baylor College of Medicine
Houston, Texas

Associate Director for Research Infrastructure

Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas

Addresses

Alkek Building for Biomedical Research (Office)

Room: ABBR-R505
Houston, TX 77030
United States
Phone: (713) 798-2326
deane@bcm.edu

Education

Post-Doctoral Fellowship at University Of Texas Health Science Center

01/1980 - San Antonio, Texas United States

EdD from Medical College of Georgia School of Graduate Studies

01/1976 - Augusta, Georgia United States

BS from Ohio University

Athens, Ohio

Honors & Awards

Editorial Review Boards

Molecular Endocrinology, J. Steroid Biochemistry and Molecular Biology, Breast Cancer Research and Treatment, Steroids

Member NIH Study Section on Molecular and Cellular Endocrinology

Dan L. Duncan Professorship

Websites

Selected Publications

• Goswami D, Callaway C, Pascal B, Kumar R, Edwards DP, Griffin PR. "The influence of domain interactions on conformational mobility of the progesterone receptor as detected by hydrogen/deuterium exchange mass spectrometry.." Structure. 2014;22(7):961-973. Pubmed PMID: 24909783
• Simons SS, Edwards DP, Kumar R. "Mini Review: Dynamic structures of nuclear hormone receptors: New promises and challenges.." Molec. Endocrinol.. 2014;28(2):173-182. Pubmed PMID: 24284822
• Obr AE, Grimm SL, Bishop KA, Pike JW, Lydon JP, Edwards DP. "Progesterone receptor and Stat5 signaling crosstalk through RANKL in mammary epithelial cells.." Molec. Endocrinol.. 2013;27(11):1808-1824. Pubmed PMID: 24014651
• Kumar R, Moure CM, Khan SH, Callaway C, Grimm S, Goswami D. Griffin PR, Edwards DP. "Regulation of the structurally dynamic amino-terminal domain of progesterone receptor by protein induced folding.." J. Biolog. Chem.. 2013;288(42):30285-30299. Pubmed PMID: 23995840

Projects

Research Laboratory

Baylor College of Medicine

My research laboratory has been funded by NIH and other major granting agencies for 34 years on the biology and molecular mechanism of action of steroid hormone receptors with a major focus on the progesterone receptor (PR). We have made many contributions to understanding the role and mechanism of action of PR, primarily in mammary gland development and in breast cancer as experimental models. In the mammary gland we revealed how progesterone (P4) stimulation of epithelial cell proliferation occurs through paracrine pathways mediated by RANKL as a PR target gene. We also defined molecular mechanisms of cross-talk between PR and Stat5 involved in regulating genes required for proliferation during early pregnancy and for suppression of terminal differentiation and lactation at late pregnancy. In breast cancer, we have made significant contributions in the area of rapid non-genomic signaling of P4 and PR on pathways that affect cell proliferation. We also defined the role of phosphorylation of PR in mediating its transcriptional activity and in modulating partial agonist activities of clinically relevant PR antagonists. A more recent interest is the role PR in early stage breast cancer, specifically transition of ductal carcinoma in situ (DCIS) to invasive breast carcinoma. We established an estrogen receptor (ER), PR positive human DCIS cell line to study molecular mechanisms and progression in a mouse intraductal xenograft model. In mice with DCIS formed by transplanted ER/PR+DCIS cells, progesterone treatment stimulated invasion of DCIS lesions, an effect blocked by the PR antagonist RU486, and invasive tumors were aggressive squamous cell-like carcinoma. As a potential molecular mechanism, progesterone activated the mTOR signaling pathway resulting in reprograming of energy metabolism and it upregulated an immunosuppressive COX2/prostaglandin E2/IL-6 pathway in DCIS cells. Another long-standing area of interest, that is most related to this application, is the fundamental structure function properties of the PR protein. Early work defined consensus progesterone response elements (PRE) of target genes recognized by PR dimers and the role of chromatin HMGB proteins, as DNA chaperones, in facilitating PR-PRE binding. We determined high resolution X-ray crystallography structures of the PR DNA binding domain (DBD) complexed with PRE DNA, revealing a novel interaction of the C- terminal extension (CTE) of the DBD with flanking minor groove sequences required for high affinity PR-PRE binding. Solution-phase biophysical methods including NMR, have been used to define binding proteins that induce folding and structural reorganization of intrinsically disorder protein (IDP) regions of the CTE and amino terminal domain (NTD) as a mechanism that facilitates AF1 transcriptional activity. Additionally, hydrogen-deuterium exchange (HDX)-mass spectrometry studies have revealed the role of allosteric coupling between receptor domains. Dr. Edwards is highly engaged as a scientific leader at Baylor College of Medicine. He is Associate Director for Research Infrastructure for the recently renewed NCI-P30 Cancer Center Support Grant of the Dan L. Duncan Comprehensive Cancer Center (DLDCCC), and serves as a member of the Executive Committee of the DLDCCC. He also serves as Executive Director of Advanced Technology Cores (ATC) at BCM providing scientific oversight, setting policies and financial and administrative management of 26 Institutional Core Facilities. Dr. Edwards is PI of a $5M CPRIT (Cancer Prevention and Research Institute) grant for a Proteomics and Metabolomics Core Facility that provides technological support and expertise for proteomic and metabolomics research for all BCM faculty interested in cancer research.

Memberships

Endocrine Society

American Association for the Advancement of Science

Association of Biomolecular Resource Facilities