Dean Edwards, Ph.D.
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Dean Edwards, Ph.D.
Professor
Positions
- Professor
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Mol & Cell Biology and Pathology & Immunology
Baylor College of Medicine
Houston, TX US
- Executive Director, Advanced Technology Cores
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Baylor College of Medicine
Houston, Texas
- Associate Director for Research Infrastructure
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Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas
Addresses
- Alkek Building for Biomedical Research (Office)
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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
- Nickisch K, Nair HB, Kesavaram N, Das B, Garfield R, Shi SQ, Bhaskaran SS, Grimm SL, Edwards DP. "Synthesis and antiprogestational properties of novel 17-fluorinated steroids.." Steroids. 2013;78(9):909-919. Pubmed PMID: 23607964
- Buser AC, Obr AE, Kabotyanski EB, Grimm SL, Rosen JM, Edwards DP "Progesterone Receptor Directly Inhibits {beta}-Casein Gene Transcription in Mammary Epithelial Cells Through Promoting Promoter and Enhancer Repressive Chromatin Modifications.." Mol. Endocrinol.. 2011 Jun;25(6):955-68. Pubmed PMID: 21527503
- Wardell SE, Narayanan R, Weigel NL, Edwards DP "Partial Agonist Activity of the Progesterone Receptor Antagonist RU486 Mediated by an Amino-Terminal Domain Coactivator and Phosphorylation of Serine400.." Mol. Endocrinol.. 2010 Feb;24(2):335-45. Pubmed PMID: 20008003
- Roemer SC, Donham DC, Sherman L, Pon VH, Edwards DP, Churchill ME "Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements.." Mol. Endocrinol.. 2006 Dec;20(12):3042-52. Pubmed PMID: 16931575
- Hill KK, Roemer SC, Jones DN, Churchill ME, Edwards DP "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.. 2009 Sep 4;284(36):24415-24. Pubmed PMID: 19553667
- Treviño LS, Bingman WE, Edwards DP, Nl W "The requirement for p42/p44 MAPK activity in progesterone receptor-mediated gene regulation is target gene-specific.." Steroids. 2013 Jun;78(6):542-7. Pubmed PMID: 23380370
- Grimm, S.L., Ward, R.D., Obr, A.E., Franco, H.L., Fernandez-Valdivia, R., Kim, J.-S., Roberts, J.M., Jeong, J.-W., DeMayo, F.J., Lydon, J.P., Edwards, D.P., and Weigel, N.L. "A role for site-specific phosphorylation of mouse progesterone receptor at Serine 191 in vivo.." Mol. Endo.. 2014;12:2025-2037. Pubmed PMID: 25333515
- Treviño LS, Bolt MJ, Grimm, SL, Edwards DP, Mancini MA, Weigel NL. "Differential Regulation of Progesterone Receptor-Mediated Transcription by CDK2 and DNA-PK.." Mol. Endo.. 2016;30:158-172. Pubmed PMID: 26652902
- Welte T, Kim IS, Tian L, Gao X, Wang H, Li J, Holdman XB, Herschkowitz JI, Pond A, Xie G, Kurley S, Nguyen T, Liao L, Dobrolecki LE, Pang L, Mo Q, Edwards DP, Huang S, Xin L, Xu J, Li Y, Lewis MT, Wang T, Westbrook TF, Rosen JM, Zhang XH. "Oncogenic mTOR signaling recruits myeloid-derived suppressor cells to promote tumour initiation.." Nat Cell Biol. 2016;18:632-644. Pubmed PMID: 27183469
- Grimm SL, Hartig SM, Edwards DP. "Progesterone receptor signaling mechanisms.." J. Mol. Biol.. 2016;428:3831-3849. Pubmed PMID: 27380738
- Elsarraj HS, Valdez KE, Hong Y, Grimm SL, Ricci LR, Fan F, Tawfik O, May L, Cusick T, Inciardi M, Redick M, Gatewood J, Winblad O, Hilsenbeck S, Edwards DP, Hagan CR, Godwin AK, Fabian C, Behbod F. "NEMO, a transcriptional target of estrogen and progesterone, is linked to tumor suppressor PML in breast cancer.." Cancer Res.. 2017;77:3802-3813. Pubmed PMID: 28515148
- Hai L, Szwarc MM, Wetendorf M, Wu SP, Peavey MC, Grimm SL, Edwards DP, DeMayo FJ, Lydon JP. "A mouse model engineered to conditionally express the progesterone receptor-B isoform.." Genesis. 2018;56:e23223. Pubmed PMID: 30004627
- Villanueva H, Grimm S, Dhamne S, Rajapakshe K, Visbal A, Davis CM, Ehli EA, Hartig SM, Coarfa C, Edwards DP. "The Emerging Roles of Steroid Hormone Receptors in Ductal Carcinoma in Situ (DCIS) of the Breast.." J Mammary Gland Biol Neoplasia. 2018;23:237-248. Pubmed PMID: 30338425
- Bu W, Liu Z, Jiang W, Nagi C, Huang S, Edwards DP, Jo E, Mo Q, Creighton CJ, Hilsenbeck SG, Leavitt AD, Lewis MT, Wong STC, Li Y. "Mammary precancerous stem and non-stem cells evolve into cancers of distinct subtypes.." Cancer Res.. 2019;79:61-71. Pubmed PMID: 30401712
- Guo Z, Primeau T, Luo J, Zhang C, Sun H, Hoog J, Gao F, Huang S, Edwards DP, Davies SR, Aft R, Ding L, Ellis MJ, Li S, Ma CX. "Proteomic Resistance Biomarkers for PI3K Inhibitor in Triple Negative Breast Cancer Patient-Derived Xenograft Models.." Cancers (Basel). 2020;12:3857. Pubmed PMID: 33371187
- Coarfa C, Grimm SL, Rajapakshe K, Perera D, Lu HY, Wang X, Christensen KR, Mo Q, Edwards DP, Huang S. "Reverse-Phase Protein Array: Technology, Application, Data Processing, and Integration.." J Biomol Tech.. 2021;15-29. Pubmed PMID: 34025221
- Holdman XB, Welte T, Rajapakshe K, Pond A, Coarfa C, Mo Q, Huang S, Hilsenbeck SG, Edwards DP, Zhang X, Rosen JM. "Upregulation of EGFR signaling is correlated with tumor stroma remodeling and tumor recurrence in FGFR1-driven breast cancer.." Breast Cancer Res.. 2015;17:141. Pubmed PMID: 26581390
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
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