Donald McDonnell

Summary

Affiliation: Duke University Medical Center
Country: USA

Publications

  1. pmc Research resource: Transcriptional profiling in a cellular model of breast cancer reveals functional and mechanistic differences between clinically relevant SERM and between SERM/estrogen complexes
    Suzanne E Wardell
    Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Box 3813, Durham, North Carolina 27710, USA
    Mol Endocrinol 26:1235-48. 2012
  2. ncbi request reprint Capitalizing on the complexities of estrogen receptor pharmacology in the quest for the perfect SERM
    D P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Ann N Y Acad Sci 949:16-35. 2001
  3. ncbi request reprint Mining the complexities of the estrogen signaling pathways for novel therapeutics
    Donald P McDonnell
    Duke University Medical Center, Box 3813, Durham, North Carolina 27710, USA
    Endocrinology 144:4237-40. 2003
  4. ncbi request reprint The molecular pharmacology of estrogen receptor modulators: implications for the treatment of breast cancer
    Donald P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Clin Cancer Res 11:871s-7s. 2005
  5. ncbi request reprint Linking ligand-induced alterations in androgen receptor structure to differential gene expression: a first step in the rational design of selective androgen receptor modulators
    Dmitri Kazmin
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Endocrinol 20:1201-17. 2006
  6. pmc 27-Hydroxycholesterol: a potential endogenous regulator of estrogen receptor signaling
    Carolyn D DuSell
    Duke University Medical Center, Department of Pharmacology and Cancer Biology, Durham, NC 27710, USA
    Trends Pharmacol Sci 29:510-4. 2008
  7. ncbi request reprint Connections and regulation of the human estrogen receptor
    Donald P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3813, Durham, NC 27710, USA
    Science 296:1642-4. 2002
  8. pmc The molecular mechanisms underlying the pharmacological actions of ER modulators: implications for new drug discovery in breast cancer
    Donald P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Curr Opin Pharmacol 10:620-8. 2010
  9. pmc The oxysterol, 27-hydroxycholesterol, links cholesterol metabolism to bone homeostasis through its actions on the estrogen and liver X receptors
    Erik R Nelson
    Pharmacology and Cancer Biology, Duke University Medical Center, P O Box 3813, Durham, North Carolina 27710, USA
    Endocrinology 152:4691-705. 2011
  10. ncbi request reprint The molecular determinants of estrogen receptor pharmacology
    Donald P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Maturitas 48:S7-12. 2004

Collaborators

Detail Information

Publications68

  1. pmc Research resource: Transcriptional profiling in a cellular model of breast cancer reveals functional and mechanistic differences between clinically relevant SERM and between SERM/estrogen complexes
    Suzanne E Wardell
    Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Box 3813, Durham, North Carolina 27710, USA
    Mol Endocrinol 26:1235-48. 2012
    ..Cumulatively, the findings of this analysis are informative with respect to the mechanisms by which ER is engaged by different enhancers/promoters and highlights how promoter context influences the pharmacological activity of ER ligands...
  2. ncbi request reprint Capitalizing on the complexities of estrogen receptor pharmacology in the quest for the perfect SERM
    D P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Ann N Y Acad Sci 949:16-35. 2001
    ....
  3. ncbi request reprint Mining the complexities of the estrogen signaling pathways for novel therapeutics
    Donald P McDonnell
    Duke University Medical Center, Box 3813, Durham, North Carolina 27710, USA
    Endocrinology 144:4237-40. 2003
  4. ncbi request reprint The molecular pharmacology of estrogen receptor modulators: implications for the treatment of breast cancer
    Donald P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Clin Cancer Res 11:871s-7s. 2005
    ....
  5. ncbi request reprint Linking ligand-induced alterations in androgen receptor structure to differential gene expression: a first step in the rational design of selective androgen receptor modulators
    Dmitri Kazmin
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Endocrinol 20:1201-17. 2006
    ..This relationship provides a firm underpinning for mechanism-based screens aimed at identifying SARMs with useful clinical profiles...
  6. pmc 27-Hydroxycholesterol: a potential endogenous regulator of estrogen receptor signaling
    Carolyn D DuSell
    Duke University Medical Center, Department of Pharmacology and Cancer Biology, Durham, NC 27710, USA
    Trends Pharmacol Sci 29:510-4. 2008
    ..These results provide an interesting potential link between cholesterol (and cholesterol metabolism) and ER function, the physiological and pathological importance of which remains to be determined...
  7. ncbi request reprint Connections and regulation of the human estrogen receptor
    Donald P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3813, Durham, NC 27710, USA
    Science 296:1642-4. 2002
    ..Thus, although the estrogen receptor is required for a cell to respond to an estrogenic stimulus, the nature and extent of that response are determined by the proteins, pathways, and processes with which the receptor interacts...
  8. pmc The molecular mechanisms underlying the pharmacological actions of ER modulators: implications for new drug discovery in breast cancer
    Donald P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Curr Opin Pharmacol 10:620-8. 2010
    ....
  9. pmc The oxysterol, 27-hydroxycholesterol, links cholesterol metabolism to bone homeostasis through its actions on the estrogen and liver X receptors
    Erik R Nelson
    Pharmacology and Cancer Biology, Duke University Medical Center, P O Box 3813, Durham, North Carolina 27710, USA
    Endocrinology 152:4691-705. 2011
    ....
  10. ncbi request reprint The molecular determinants of estrogen receptor pharmacology
    Donald P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Maturitas 48:S7-12. 2004
    ..This review describes how these advances have impacted our understanding of the pharmacologic activities of currently available ER ligands...
  11. ncbi request reprint Identification of a negative regulatory surface within estrogen receptor alpha provides evidence in support of a role for corepressors in regulating cellular responses to agonists and antagonists
    Huey Jing Huang
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Endocrinol 16:1778-92. 2002
    ..In addition, our data suggest that corepressors, other than NCoR/SMRT, may be involved in ER signaling...
  12. ncbi request reprint A negative coregulator for the human ER
    John D Norris
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Endocrinol 16:459-68. 2002
    ..These findings suggest a role for RNA binding proteins as coregulatory factors of the nuclear receptor family and reveal a novel mechanism by which antiestrogens can manifest agonist activities in some tissues...
  13. ncbi request reprint Definition of functionally important mechanistic differences among selective estrogen receptor down-regulators
    Bryan M Wittmann
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, 27710, USA
    Cancer Res 67:9549-60. 2007
    ....
  14. ncbi request reprint Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting
    Julie M Hall
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Mol Interv 5:343-57. 2005
    ..This review also describes current efforts aimed at developing pharmaceutical agents that target ER-cofactor interactions as therapeutics for estrogen-associated pathologies...
  15. ncbi request reprint Application of random peptide phage display to the study of nuclear hormone receptors
    Ching Yi Chang
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Methods Enzymol 364:118-42. 2003
  16. pmc Regulation of aryl hydrocarbon receptor function by selective estrogen receptor modulators
    Carolyn D DuSell
    Duke University Medical Center, Department of Pharmacology and Cancer Biology, Durham, North Carolina 27710, USA
    Mol Endocrinol 24:33-46. 2010
    ..Cumulatively, these findings provide evidence that it is necessary to reevaluate the relative roles of ER and AHR in manifesting the pharmacological actions and therapeutic efficacy of TAM and other SERMs...
  17. ncbi request reprint Direct interactions between corepressors and coactivators permit the integration of nuclear receptor-mediated repression and activation
    Xiaolin Li
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Endocrinol 16:1482-91. 2002
    ..It is proposed, therefore, that TRbeta- mediated activation and repression are integrally linked in a manner that is not predicted by the current models of nuclear receptor action...
  18. ncbi request reprint Definition of the molecular basis for estrogen receptor-related receptor-alpha-cofactor interactions
    Stephanie Gaillard
    Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Endocrinol 21:62-76. 2007
    ....
  19. ncbi request reprint Expression of functional estrogen receptor beta in locus coeruleus-derived Cath.a cells
    Heather L Rincavage
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Endocrinology 144:2829-35. 2003
    ..Cath.a cells may prove to be a useful tool in elucidating basic pharmacologic properties of ERbeta. It may also help reveal the molecular mechanisms involved in mood regulation by estrogen...
  20. ncbi request reprint Definition of the molecular and cellular mechanisms underlying the tissue-selective agonist/antagonist activities of selective estrogen receptor modulators
    Donald P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Recent Prog Horm Res 57:295-316. 2002
    ..This realization has provided the impetus for research in this area, the progress of which is discussed in this review...
  21. ncbi request reprint Elucidation of the molecular mechanism of action of selective estrogen receptor modulators
    Donald P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Am J Cardiol 90:35F-43F. 2002
    ..This realization has provided the impetus for research in this area, the progress of which is described in this review...
  22. pmc Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells
    John P Chute
    Division of Cellular Therapy, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 103:11707-12. 2006
    ..Modulation of ALDH activity and retinoid signaling is a previously unrecognized and effective strategy to amplify human HSCs...
  23. pmc Minireview: Nuclear receptors, hematopoiesis, and stem cells
    John P Chute
    Division of Cellular Therapy, Department of Medicine, Duke University, Durham, North Carolina 27710, USA
    Mol Endocrinol 24:1-10. 2010
    ..Herein, we review in detail the function of specific NRs in controlling HSC and other stem cell fate and propose a framework through which these observations can be translated into therapeutic amplification of HSCs for clinical purposes...
  24. pmc Pharmacological manipulation of the RAR/RXR signaling pathway maintains the repopulating capacity of hematopoietic stem cells in culture
    Rachid Safi
    Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina 27710, USA
    Mol Endocrinol 23:188-201. 2009
    ..These data indicate that the RAR/RXR heterodimer is a critical regulator of human HSC differentiation, and pharmacological modulation of RXR signaling prevents the loss of human HSCs that otherwise occurs in short-term culture...
  25. ncbi request reprint Mechanism-based discovery as an approach to identify the next generation of estrogen receptor modulators
    Donald P McDonnell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, 6259 LSRC, Box 3813, Durham, NC 27710, USA
    FASEB J 20:2432-4. 2006
  26. pmc The endogenous selective estrogen receptor modulator 27-hydroxycholesterol is a negative regulator of bone homeostasis
    Carolyn D DuSell
    Department of Pharmacology, Duke University Medical Center, Pharmacology and Cancer Biology, Durham, North Carolina 27710, USA
    Endocrinology 151:3675-85. 2010
    ..More studies are warranted to fully elucidate the mechanism of action of 27HC in bone and to identify ways to modulate this pathway therapeutically...
  27. ncbi request reprint Identification and characterization of novel estrogen receptor-beta-sparing antiprogestins
    Ganesan Sathya
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Endocrinology 143:3071-82. 2002
    ..It is anticipated that the availability of these new antiprogestins will advance the studies of PR pharmacology in a manner similar to how the availability of selective ER modulators has helped the study of ER action...
  28. pmc 27-hydroxycholesterol is an endogenous selective estrogen receptor modulator
    Carolyn D DuSell
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Endocrinol 22:65-77. 2008
    ..Moreover, given the product-precursor relationship between 27HC and cholesterol, our findings have implications with respect to breast cancer risk in obese/hypercholesteremic individuals...
  29. pmc Multimodal regulation of E2F1 gene expression by progestins
    Hilary E Wade
    Duke University Medical Center, Department of Pharmacology and Cancer Biology, Durham, NC 27710, USA
    Mol Cell Biol 30:1866-77. 2010
    ..Taken together, these results suggest a new paradigm for multimodal regulation of target gene expression by PR...
  30. pmc Estrogen-related receptor alpha induces the expression of vascular endothelial growth factor in breast cancer cells
    Rebecca A Stein
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3813, Durham, NC 27710, United States
    J Steroid Biochem Mol Biol 114:106-12. 2009
    ..These findings suggest that ERRalpha-dependent induction of VEGF may contribute to the overall negative phenotype observed in tumors in which ERRalpha is expressed and provide validation for its use as a therapeutic target in cancer...
  31. pmc The homeodomain protein HOXB13 regulates the cellular response to androgens
    John D Norris
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Mol Cell 36:405-16. 2009
    ..The profound effects of HOXB13 knockdown on androgen-regulated proliferation, migration, and lipogenesis in prostate cancer cells highlight the importance of the observed changes in gene expression...
  32. doi request reprint Inhibition of aldehyde dehydrogenase expands hematopoietic stem cells with radioprotective capacity
    Garrett G Muramoto
    Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    Stem Cells 28:523-34. 2010
    ..Pharmacologic inhibition of ALDH has therapeutic potential as a means to amplify ST-HSCs for transplantation purposes...
  33. ncbi request reprint Androgen receptor-cofactor interactions as targets for new drug discovery
    Ching Yi Chang
    Duke University Medical Center, Department of Pharmacology and Cancer Biology, Durham, NC 27710, USA
    Trends Pharmacol Sci 26:225-8. 2005
    ..Recent crystallographic analysis of one of the major protein-protein interaction surfaces on the androgen receptor has raised expectations that it will be possible to develop small-molecule antagonists that block cofactor interactions...
  34. ncbi request reprint Development of peptide antagonists for the androgen receptor using combinatorial peptide phage display
    Ching Yi Chang
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3813, Durham, North Carolina 27710, USA
    Mol Endocrinol 19:2478-90. 2005
    ..Based on our findings, we believe that molecules that function by disrupting the androgen receptor-cofactor interactions will have use in the treatment of prostate cancer...
  35. ncbi request reprint Coactivation of liver receptor homologue-1 by peroxisome proliferator-activated receptor gamma coactivator-1alpha on aromatase promoter II and its inhibition by activated retinoid X receptor suggest a novel target for breast-specific antiestrogen therapy
    Rachid Safi
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Cancer Res 65:11762-70. 2005
    ..We infer from these data that LRH-1 is a bona fide target whose inhibition would selectively block aromatase expression in breast, while sparing other sites of expression...
  36. pmc Inhibition of prostate cancer cell growth by second-site androgen receptor antagonists
    James D Joseph
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 106:12178-83. 2009
    ....
  37. ncbi request reprint Evaluation of ligand-dependent changes in AR structure using peptide probes
    Ching Yi Chang
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Endocrinol 16:647-60. 2002
    ..Thus, we believe that resistance in certain prostate cancers occurs as a consequence of receptor mutations that enable antagonist-and/or nonclassical ligand-bound AR to present a wild-type-like AF-2 conformation...
  38. ncbi request reprint The nuclear receptor-coactivator interaction surface as a target for peptide antagonists of the peroxisome proliferator-activated receptors
    Niharika B Mettu
    Duke University Medical Center, Department of Pharmacology and Cancer Biology, Box 3813, Durham, North Carolina 27710, USA
    Mol Endocrinol 21:2361-77. 2007
    ..This work lends support for the rational development of peptidomimetics that block receptor-mediated transcription by targeting the nuclear receptor-coactivator interaction surface...
  39. ncbi request reprint Receptor-selective coactivators as tools to define the biology of specific receptor-coactivator pairs
    Stephanie Gaillard
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell 24:797-803. 2006
    ..In this study, we describe the customization of PGC-1alpha and its use to study the biology of the estrogen-related receptor alpha (ERRalpha) in cultured liver cells...
  40. pmc The transcription factor B-Myb is maintained in an inhibited state in target cells through its interaction with the nuclear corepressors N-CoR and SMRT
    Xiaolin Li
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 22:3663-73. 2002
    ..Cumulatively, these findings suggest that the nuclear corepressors N-CoR and SMRT serve a previously unappreciated role as regulators of B-Myb transcriptional activity...
  41. pmc Estrogen-related receptor alpha is critical for the growth of estrogen receptor-negative breast cancer
    Rebecca A Stein
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Cancer Res 68:8805-12. 2008
    ..Our results confirm a role for ERRalpha in breast cancer growth and highlight it as a potential therapeutic target for estrogen receptor-negative breast cancer...
  42. ncbi request reprint Characterization of transcriptional activation and DNA-binding functions in the hinge region of the vitamin D receptor
    Paul L Shaffer
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 44:2678-85. 2005
    ..The ability to delete more of the RXR hinge may be related to the additional plasticity required by its role as the common heterodimer partner for nuclear receptors on differing DNA elements...
  43. pmc Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha
    Linda L Grasfeder
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Endocrinol 23:1171-82. 2009
    ..These data suggest that DHEA could be playing a role as an intracellular signaling molecule involved in modulating hepatic activity in response to fasting conditions...
  44. pmc Short-chain fatty acids enhance nuclear receptor activity through mitogen-activated protein kinase activation and histone deacetylase inhibition
    Michelle S Jansen
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 101:7199-204. 2004
    ..Furthermore, our study highlights the need to structure future screening programs to identify additional hormone sensitizers...
  45. doi request reprint Differential effects of prostate cancer therapeutics on neuroendocrine transdifferentiation
    Daniel E Frigo
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Mol Cancer Ther 7:659-69. 2008
    ..Taken together, these data show that the phenotypic responses to pharmacologic agents used in the clinic to prevent the progression of prostate cancer are not equivalent, a finding of significant therapeutic importance...
  46. ncbi request reprint Pharmacological uncoupling of androgen receptor-mediated prostate cancer cell proliferation and prostate-specific antigen secretion
    Ganesan Sathya
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Cancer Res 63:8029-36. 2003
    ..The unexpected finding that AR-mediated transcription and proliferation can be uncoupled suggests that AR is not used in the same manner in all androgen-regulated biological processes...
  47. pmc Induction of Kruppel-like factor 5 expression by androgens results in increased CXCR4-dependent migration of prostate cancer cells in vitro
    Daniel E Frigo
    Duke University Medical Center, Department of Pharmacology, Box 3813, Durham, North Carolina 27710, USA
    Mol Endocrinol 23:1385-96. 2009
    ....
  48. pmc Development of a small-molecule serum- and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic
    Andrea B Sherk
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA
    Cancer Res 68:7475-83. 2008
    ..Thus, in addition to androgen ablation, inhibition of pathways downstream of AR is likely to have therapeutic utility in prostate cancer...
  49. ncbi request reprint Common estrogen receptor polymorphism augments effects of hormone replacement therapy on E-selectin but not C-reactive protein
    David M Herrington
    Department of Internal Medicine, Wake Forest University School of Medicine, Winston Salem, NC 27157 1045, USA
    Circulation 105:1879-82. 2002
    ..This study sought to determine if this augmentation extends to HRT regulation of E-selectin and C-reactive protein (CRP) and to explore possible mechanisms by which this polymorphism might influence estrogen action...
  50. ncbi request reprint Proceedings of the Fourth International Conference on Recent Advances and Future Directions in Endocrine Manipulation of Breast Cancer: conference summary statement
    Steven E Come
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
    Clin Cancer Res 11:861s-4s. 2005
  51. ncbi request reprint Increased expression of estrogen receptor beta in pachytene spermatocytes after short-term methoxyacetic acid administration
    Oscar M Tirado
    Unitat de Recerca Biomedica, Hospital Materno Infantil Vall d Hebron, Barcelona, Spain
    J Androl 25:84-94. 2004
    ..Whether MAA interacts with ERbeta in the cytoplasm of primary spermatocytes, preventing the progression of the first meiotic division, however, remains to be determined...
  52. pmc Coactivator AIB1 links estrogen receptor transcriptional activity and stability
    Wenlin Shao
    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:11599-604. 2004
    ....
  53. ncbi request reprint Hormone therapy: physiological complexity belies therapeutic simplicity
    Judith L Turgeon
    Department of Internal Medicine, Division of Endocrinology, Clinical Nutrition, and Vascular Medicine, University of California Davis, Davis, CA 95616, USA
    Science 304:1269-73. 2004
    ....
  54. ncbi request reprint Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRgamma
    Esther Y H Chao
    Discovery Research, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA
    Bioorg Med Chem Lett 16:821-4. 2006
    ..An X-ray crystal structure of one of the designed compounds bound to ERRgamma LBD confirms the molecular basis of the selectivity...
  55. ncbi request reprint Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity
    Isaac H Solomon
    Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    J Mol Biol 354:1091-102. 2005
    ..Taken together, these results indicate that subtle structural changes in a nuclear receptor DBD can exert long-range functional effects on the LBD of a receptor, and significantly impact transcriptional regulation...
  56. ncbi request reprint Structural basis for an unexpected mode of SERM-mediated ER antagonism
    Ya Ling Wu
    The Ben May Institute for Cancer Research and Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA
    Mol Cell 18:413-24. 2005
    ..This dual mechanism of antagonism may explain why GW5638 can inhibit tamoxifen-resistant breast tumors...
  57. ncbi request reprint Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression
    Yi Zhang
    Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    J Biol Chem 281:39897-906. 2006
    ..Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter. Our data demonstrate a key role for the ERRs in the induction of hepatic PDK4 gene expression...
  58. ncbi request reprint Identification and structure-activity relationship of phenolic acyl hydrazones as selective agonists for the estrogen-related orphan nuclear receptors ERRbeta and ERRgamma
    William J Zuercher
    Discovery Research, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, North Carolina 27707, USA
    J Med Chem 48:3107-9. 2005
    ..Notably, in cell-based reporter assays, 3 mimics the protein ligand PGC-1alpha in activation of human ERRbeta and ERRgamma...
  59. ncbi request reprint Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP
    Eric A Ortlund
    Department of Chemistry, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, 27599, USA
    Nat Struct Mol Biol 12:357-63. 2005
    ..Our results indicate that hLRH-1's control of gene expression is mediated by phospholipid binding, and establish hLRH-1 as a novel target for compounds designed to slow breast cancer development...
  60. pmc The vitamin D receptor interacts preferentially with DRIP205-like LxxLL motifs
    Lee A Zella
    Department of Biochemistry, University of Wisconsin Madison, 433 Babcock Drive, Madison, WI 53706, USA
    Arch Biochem Biophys 460:206-12. 2007
    ..These studies suggest that the LxxLL motif can interact directly with the VDR and that this interaction is regulated by chemically diverse vitamin D ligands...
  61. ncbi request reprint International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors
    Nick Z Lu
    Molecular Endocrinology Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA
    Pharmacol Rev 58:782-97. 2006
  62. ncbi request reprint Allosteric regulation of estrogen receptor structure, function, and coactivator recruitment by different estrogen response elements
    Julie M Hall
    Receptor Biology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Mol Endocrinol 16:469-86. 2002
    ....
  63. pmc Human PXR forms a tryptophan zipper-mediated homodimer
    Schroeder M Noble
    Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Biochemistry 45:8579-89. 2006
    ..Taken together, these results suggest that the unique Trp-Zip-mediated PXR homodimer plays a role in the function of this nuclear xenobiotic receptor...
  64. ncbi request reprint Selective LXXLL peptides antagonize transcriptional activation by the retinoid-related orphan receptor RORgamma
    Shogo Kurebayashi
    Cell Biology Section, Division of Intramural Research, National Institute of Environmental Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Biochem Biophys Res Commun 315:919-27. 2004
    ..These peptide antagonists provide a useful tool to analyze the conformation changes in the RORgamma(LBD) and to study RORgamma receptor signaling...
  65. pmc On the intractability of estrogen-related receptor alpha as a target for activation by small molecules
    Stephen M Hyatt
    Molecular Discovery Research Branch, GlaxoSmithKline, Research Triangle Park, NC 27709, USA
    J Med Chem 50:6722-4. 2007
    ..The results suggest that ERRalpha may be intractable as a direct target for pharmacologic activation...
  66. ncbi request reprint Inhibition of 1,25-dihydroxyvitamin D3-dependent transcription by synthetic LXXLL peptide antagonists that target the activation domains of the vitamin D and retinoid X receptors
    Peterson Pathrose
    Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, USA
    J Bone Miner Res 17:2196-205. 2002
    ..This approach may represent a novel means of assessing the contribution of RXR in various endogenous biological responses to 1,25(OH)2D3...
  67. ncbi request reprint Synthetic LXXLL peptide antagonize 1,25-dihydroxyvitamin D3-dependent transcription
    J Wesley Pike
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Cell Biochem 88:252-8. 2003
    ..This approach may represent a novel means of assessing the contribution of RXR in various endogenous biological responses to 1,25(OH)(2)D(3)...

Research Grants43

  1. Conference on Tissue-Selective Nuclear Receptors
    Donald McDonnell; Fiscal Year: 2004
    ..The meeting will center upon our understanding of a class of transcription factors whose pharmacology touches some of the most prevalent human diseases ..
  2. Molecular Determinants of Androgen Receptor Pharmacology
    Donald P McDonnell; Fiscal Year: 2010
    ..In this project, we outline a basic research program aimed at identifying new targets in prostate cancer that will be amenable to therapeutic intervention. ..
  3. Validation of the Estrogen Related Receptor as a therapeutic target in cancer
    Donald P McDonnell; Fiscal Year: 2011
    ..In this study we propose to use both cellular and animal models to assess the cause and effect relationship between ERR1 activity and the pathophysiology of both ER1-positive and ER1-negative tumors. ..
  4. Molecular Determinants of Androgen Receptor Pharmacology
    Donald McDonnell; Fiscal Year: 2006
    ..abstract_text> ..
  5. Development of peptide antagonists of estrogen signaling
    Donald McDonnell; Fiscal Year: 2005
    ..In particular, we see that this approach would be applicable to the treatment of anti-androgen resistant prostate cancers where receptor mutations enable the inappropriate recruitment of transcription coactivators. ..
  6. Nuclear Receptors: Steroid Sisters
    Donald McDonnell; Fiscal Year: 2004
    ..abstract_text> ..
  7. GENETIC DISSECTION OF PROGESTERONE RECEPTOR FUNCTION
    Donald McDonnell; Fiscal Year: 2004
    ..3) Definition of the molecular mechanism of action of the selective progesterone receptor modulators (SPRMs). (4) Identification of cellular factors which modulate PR-pharmacology. ..
  8. MECHANISM OF ACTION OF ESTROGENS AND ANTIESTROGENS
    Donald McDonnell; Fiscal Year: 2007
    ..Aim 4. Definition of the molecular mechanism by which the RNA binding protein RTAalpha/FXH-1 manifests its regulatory activity on ERalpha pharmacology. ..
  9. Validation of the Estrogen Related Receptor as a therapeutic target in cancer
    Donald P McDonnell; Fiscal Year: 2010
    ..It now appears, however, that activities unrelated to ER signaling are an equally important facet of ERR biology. Most notably, it has been shown that ERR is a ..
  10. Molecular Determinants of Androgen Receptor Pharmacology
    Donald P McDonnell; Fiscal Year: 2011
    ..In this project, we outline a basic research program aimed at identifying new targets in prostate cancer that will be amenable to therapeutic intervention. ..
  11. The pharmacological actions of antiprogestins in uterine fibroids
    Donald P McDonnell; Fiscal Year: 2010
    ..abstract_text> ..
  12. Validation of the Estrogen Related Receptor as a therapeutic target in cancer
    Donald P McDonnell; Fiscal Year: 2010
    ..In this study we propose to use both cellular and animal models to assess the cause and effect relationship between ERR1 activity and the pathophysiology of both ER1-positive and ER1-negative tumors. ..
  13. MECHANISM OF ESTROGENS AND ANTIESTROGENS
    Donald McDonnell; Fiscal Year: 2004
    ..abstract_text> ..
  14. MECHANISM OF ACTION OF ESTROGENS AND ANTIESTROGENS
    Donald McDonnell; Fiscal Year: 1999
    ..We hypothesize that alterations in the expression level or genetic alterations in the proteins that constitute the basal transcription apparatus can determine whether tamoxifen will function as a receptor antagonist or not. ..
  15. GENETIC DISSECTION OF PROGESTERONE RECEPTOR FUNCTION
    Donald McDonnell; Fiscal Year: 1999
    ....