David J Mangelsdorf

Summary

Affiliation: University of Texas Southwestern Medical Center
Country: USA

Publications

  1. ncbi request reprint Prevention of cholesterol gallstone disease by FXR agonists in a mouse model
    Antonio Moschetta
    Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390 9050, USA
    Nat Med 10:1352-8. 2004
  2. pmc AKR1B7 is induced by the farnesoid X receptor and metabolizes bile acids
    Daniel R Schmidt
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 286:2425-32. 2011
  3. pmc FGF21 regulates metabolism and circadian behavior by acting on the nervous system
    Angie L Bookout
    1 Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA 2 Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Nat Med 19:1147-52. 2013
  4. doi request reprint Commentary: the year in nuclear receptor control of metabolism
    David J Mangelsdorf
    University of Texas Southwestern Medical Center, Howard Hughes Medical Institute, Department of Pharmacology, 6001 Forest Park Road, Room ND9 124A, Dallas, TX 75390 9050, USA
    Mol Endocrinol 24:2075-80. 2010
  5. pmc FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response
    Matthew J Potthoff
    Department of Pharmacology, Howard Hughes Medical Institute, Advanced Imaging Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 106:10853-8. 2009
  6. pmc Liver receptor homolog-1 regulates bile acid homeostasis but is not essential for feedback regulation of bile acid synthesis
    Youn Kyoung Lee
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    Mol Endocrinol 22:1345-56. 2008
  7. pmc FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α pathway
    Matthew J Potthoff
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Cell Metab 13:729-38. 2011
  8. pmc Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor
    Takeshi Inagaki
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 103:3920-5. 2006
  9. pmc Regulation of bile acid synthesis by fat-soluble vitamins A and D
    Daniel R Schmidt
    Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9050, USA
    J Biol Chem 285:14486-94. 2010
  10. pmc FGF21 contributes to neuroendocrine control of female reproduction
    Bryn M Owen
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Nat Med 19:1153-6. 2013

Research Grants

  1. Conference on Nuclear Receptor Superfamily
    David Mangelsdorf; Fiscal Year: 2002
  2. Nuclear Receptors: Orphan Brothers
    David Mangelsdorf; Fiscal Year: 2004
  3. MECHANISMS OF DRUG ACTION AND DISPOSITION
    David Mangelsdorf; Fiscal Year: 2007

Collaborators

Detail Information

Publications65

  1. ncbi request reprint Prevention of cholesterol gallstone disease by FXR agonists in a mouse model
    Antonio Moschetta
    Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390 9050, USA
    Nat Med 10:1352-8. 2004
    ..Taken together, these results indicate that FXR is a promising therapeutic target for treating or preventing cholesterol gallstone disease...
  2. pmc AKR1B7 is induced by the farnesoid X receptor and metabolizes bile acids
    Daniel R Schmidt
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 286:2425-32. 2011
    ..These findings reveal a feed-forward, protective pathway operative in murine enterohepatic tissues wherein FXR induces AKR1B7 to detoxify bile acids...
  3. pmc FGF21 regulates metabolism and circadian behavior by acting on the nervous system
    Angie L Bookout
    1 Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA 2 Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Nat Med 19:1147-52. 2013
    ..These findings demonstrate a crucial role for the nervous system in mediating the diverse physiologic and pharmacologic actions of FGF21. ..
  4. doi request reprint Commentary: the year in nuclear receptor control of metabolism
    David J Mangelsdorf
    University of Texas Southwestern Medical Center, Howard Hughes Medical Institute, Department of Pharmacology, 6001 Forest Park Road, Room ND9 124A, Dallas, TX 75390 9050, USA
    Mol Endocrinol 24:2075-80. 2010
    ..These final selections were presented at "The Year In Basic Science Session" of the Annual Meeting of the Endocrine Society, ENDO 2010, the highlights of which are reproduced in this article...
  5. pmc FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response
    Matthew J Potthoff
    Department of Pharmacology, Howard Hughes Medical Institute, Advanced Imaging Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 106:10853-8. 2009
    ..These results reveal an unexpected relationship between FGF21 and PGC-1alpha and demonstrate an important role for FGF21 in coordinately regulating carbohydrate and fatty acid metabolism during the progression from fasting to starvation...
  6. pmc Liver receptor homolog-1 regulates bile acid homeostasis but is not essential for feedback regulation of bile acid synthesis
    Youn Kyoung Lee
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    Mol Endocrinol 22:1345-56. 2008
    ..Taken together, these data reveal a broad role for LRH-1 in regulating bile acid homeostasis but demonstrate that LRH-1 is either not involved in the feedback regulation of bile acid synthesis or is compensated for by other factors...
  7. pmc FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α pathway
    Matthew J Potthoff
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Cell Metab 13:729-38. 2011
    ..Overexpression of PGC-1α blocks the inhibitory effect of FGF15/19 on gluconeogenic gene expression. These results demonstrate that FGF15/19 works subsequent to insulin as a postprandial regulator of hepatic carbohydrate homeostasis...
  8. pmc Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor
    Takeshi Inagaki
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 103:3920-5. 2006
    ....
  9. pmc Regulation of bile acid synthesis by fat-soluble vitamins A and D
    Daniel R Schmidt
    Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9050, USA
    J Biol Chem 285:14486-94. 2010
    ..These results reveal an unexpected link between the intake of fat-soluble vitamins A and D and bile acid metabolism, which may have evolved as a means for these dietary vitamins to regulate their own absorption...
  10. pmc FGF21 contributes to neuroendocrine control of female reproduction
    Bryn M Owen
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Nat Med 19:1153-6. 2013
    ..Thus, FGF21 defines an important liver-neuroendocrine axis that modulates female reproduction in response to nutritional challenge. ..
  11. ncbi request reprint Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21
    Takeshi Inagaki
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Cell Metab 5:415-25. 2007
    ..These findings demonstrate an unexpected role for the PPARalpha-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation...
  12. ncbi request reprint Identification of a hormonal basis for gallbladder filling
    Mihwa Choi
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
    Nat Med 12:1253-5. 2006
    ..These studies demonstrate that gallbladder filling is actively regulated by an endocrine pathway and suggest a postprandial timing mechanism that controls gallbladder motility...
  13. pmc Liver X receptors regulate adrenal cholesterol balance
    Carolyn L Cummins
    Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9050, USA
    J Clin Invest 116:1902-12. 2006
    ..These results imply LXRalpha provides a safety valve to limit free cholesterol levels as a basal protective mechanism in the adrenal gland, where cholesterol is under constant flux...
  14. pmc Liver LXRα expression is crucial for whole body cholesterol homeostasis and reverse cholesterol transport in mice
    Yuan Zhang
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Invest 122:1688-99. 2012
    ..In sum, these observations suggest that therapeutic strategies that bypass the liver or limit the activation of hepatic LXRs should still be beneficial for the treatment of cardiovascular disease...
  15. pmc Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γ
    Wei Wei
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 109:3143-8. 2012
    ..Therefore, FGF21 is a critical rheostat for bone turnover and a key integrator of bone and energy metabolism. These results reveal that skeletal fragility may be an undesirable consequence of chronic FGF21 administration...
  16. pmc βKlotho is required for fibroblast growth factor 21 effects on growth and metabolism
    Xunshan Ding
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Cell Metab 16:387-93. 2012
    ..Taken together, these data demonstrate that βKlotho is essential for FGF21 activity and that βKlotho in adipose tissue contributes to the beneficial metabolic actions of FGF21...
  17. pmc Nuclear receptors HNF4α and LRH-1 cooperate in regulating Cyp7a1 in vivo
    Serkan Kir
    Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
    J Biol Chem 287:41334-41. 2012
    ..These findings demonstrate that both HNF4α and LRH-1 are important regulators of Cyp7a1 transcription in vivo...
  18. ncbi request reprint FXR agonists and FGF15 reduce fecal bile acid excretion in a mouse model of bile acid malabsorption
    Diana Jung
    Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9050, USA
    J Lipid Res 48:2693-700. 2007
    ..These findings suggest that FXR agonists or FGF15 could be used therapeutically to interrupt the cycle of excessive bile acid production in patients with bile acid malabsorption...
  19. ncbi request reprint Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands
    Chendong Yang
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, 75390, USA
    J Biol Chem 281:27816-26. 2006
    ..These observations are consistent with specific intermediates in the cholesterol biosynthetic pathway regulating lipid homeostasis through both the LXR and sterol response element-binding protein pathways...
  20. pmc The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder filling
    Tingting Li
    Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390 9050, USA
    Mol Endocrinol 25:1066-71. 2011
    ..They further suggest that TGR5 agonists should be assessed for effects on human gallbladder as they are developed for treating metabolic disease...
  21. ncbi request reprint Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
    Takeshi Inagaki
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Cell Metab 2:217-25. 2005
    ..These studies define FGF15 and FGFR4 as components of a gut-liver signaling pathway that synergizes with SHP to regulate bile acid synthesis...
  22. ncbi request reprint Structural determinants of allosteric ligand activation in RXR heterodimers
    Andrew I Shulman
    Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Cell 116:417-29. 2004
    ..These results reveal a structural network required for RXR heterodimer allosteric communication and suggest that the specificity of ligand response and permissivity coevolved to enable signal discrimination...
  23. pmc Identification of the nuclear receptor DAF-12 as a therapeutic target in parasitic nematodes
    Zhu Wang
    Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 106:9138-43. 2009
    ..stercoralis DAF-12 ligand-binding domain cocrystallized with dafachronic acids. These results reveal the molecular basis for DAF-12 ligand binding and identify nuclear receptors as unique therapeutic targets in parasitic nematodes...
  24. ncbi request reprint A role for the apoptosis inhibitory factor AIM/Spalpha/Api6 in atherosclerosis development
    Satoko Arai
    Center for Immunology, The University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard NA7200, Dallas, Texas 75390, USA
    Cell Metab 1:201-13. 2005
    ..We conclude that AIM production facilitates macrophage survival within atherosclerotic lesions and that loss of AIM decreases early lesion development by increasing macrophage apoptosis...
  25. ncbi request reprint A Nuclear Receptor Atlas: macrophage activation
    Grant D Barish
    Howard Hughes Medical Institute, The Salk Institute for Biological Studies, P O Box 85800, San Diego, California 92186 5800, USA
    Mol Endocrinol 19:2466-77. 2005
    ....
  26. ncbi request reprint Liver X receptor-dependent repression of matrix metalloproteinase-9 expression in macrophages
    Antonio Castrillo
    Howard Hughes Medical Institute, University of California, Los Angeles 90095, USA
    J Biol Chem 278:10443-9. 2003
    ..These observations identify the regulation of macrophage MMP-9 expression as a mechanism whereby activation of LXRs may impact macrophage inflammatory responses...
  27. pmc Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse
    Klementina Fon Tacer
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Mol Endocrinol 24:2050-64. 2010
    ..This FGF atlas provides an important resource for guiding future studies to elucidate the physiological functions of FGFs in adult animals...
  28. pmc FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis
    Serkan Kir
    Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA
    Science 331:1621-4. 2011
    ..FGF19 treatment restored the loss of glycogen in diabetic animals lacking insulin. Thus, FGF19 activates a physiologically important, insulin-independent endocrine pathway that regulates hepatic protein and glycogen metabolism...
  29. pmc Inhibition of growth hormone signaling by the fasting-induced hormone FGF21
    Takeshi Inagaki
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Cell Metab 8:77-83. 2008
    ..Chronic exposure to FGF21 markedly inhibits growth in mice. These data suggest a central role for FGF21 in inhibiting growth as part of its broader role in inducing the adaptive response to starvation...
  30. pmc Expression profiling of nuclear receptors in human and mouse embryonic stem cells
    Chang Qing Xie
    Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
    Mol Endocrinol 23:724-33. 2009
    ..These data should provide a unique resource for further exploration of the species-specific roles of NRs in ESC self-renewal and differentiation...
  31. pmc Colesevelam suppresses hepatic glycogenolysis by TGR5-mediated induction of GLP-1 action in DIO mice
    Matthew J Potthoff
    Departments of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Am J Physiol Gastrointest Liver Physiol 304:G371-80. 2013
    ..We conclude that colesevelam administration functions through a dual mechanism, which includes TGR5/GLP-1-dependent suppression of hepatic glycogenolysis and FXR-dependent cholesterol reduction...
  32. pmc Fibroblast growth factor-21 regulates PPARγ activity and the antidiabetic actions of thiazolidinediones
    Paul A Dutchak
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9041, USA
    Cell 148:556-67. 2012
    ..Adding back FGF21 prevents sumoylation and restores PPARγ activity. Collectively, these results reveal FGF21 as a key mediator of the physiologic and pharmacologic actions of PPARγ...
  33. ncbi request reprint Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network
    Angie L Bookout
    Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, 75390, USA
    Cell 126:789-99. 2006
    ..These data reveal a hierarchical transcriptional circuitry that extends beyond individual tissues to form a meganetwork governing physiology on an organismal scale...
  34. ncbi request reprint Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretion
    Liqing Yu
    McDermott Center for Human Growth and Development, Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Biol Chem 280:8742-7. 2005
    ..Thus G5 and G8 are required to modulate biliary cholesterol secretion in response to cholate and diosgenin, but the choleretic effects of these two steroids are mediated by different mechanisms requiring FXR and PXR, respectively...
  35. ncbi request reprint 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen
    Michihisa Umetani
    Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390 9050, USA
    Nat Med 13:1185-92. 2007
    ..Taken together, these studies point to 27HC as a contributing factor in the loss of estrogen protection from vascular disease...
  36. ncbi request reprint LXRs regulate the balance between fat storage and oxidation
    Nada Y Kalaany
    Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
    Cell Metab 1:231-44. 2005
    ..These studies suggest that, by selectively sensing the cholesterol component of a lipid-rich diet, LXRs govern the balance between storage and oxidation of dietary fat...
  37. pmc Fibroblast growth factor 21: from pharmacology to physiology
    Steven A Kliewer
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 73590 9041, USA
    Am J Clin Nutr 91:254S-257S. 2010
    ..This article highlights recent advances in our understanding of FGF21's pharmacologic and physiologic actions...
  38. pmc Nuclear receptor LRH-1 induces the reproductive neuropeptide kisspeptin in the hypothalamus
    Stan D Atkin
    Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Room ND9 124, Dallas, Texas 75390 9041, USA
    Mol Endocrinol 27:598-605. 2013
    ..These studies provide a molecular basis for the differential regulation of basal kisspeptin expression in Arc and AVPV neurons and reveal a prominent role for LRH-1 in hypothalamus in regulating the female reproductive axis...
  39. pmc LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function
    Sam R Holmstrom
    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Genes Dev 25:1674-9. 2011
    ..Thus, LRH-1 is a key regulator of the exocrine pancreas-specific transcriptional network required for the production and secretion of pancreatic fluid...
  40. pmc Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice
    Wenling Chen
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Cell Metab 5:73-9. 2007
    ..We conclude that oxysterols are in vivo ligands for LXR...
  41. ncbi request reprint LuXuRies of lipid homeostasis: the unity of nuclear hormone receptors, transcription regulation, and cholesterol sensing
    Yuan Zhang
    Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9050, USA
    Mol Interv 2:78-87. 2002
    ..These findings define LXRs as potential therapeutic targets for the treatment of lipid disorders...
  42. pmc MicroRNA let-7 regulates 3T3-L1 adipogenesis
    Tingwan Sun
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, 75390 9050, USA
    Mol Endocrinol 23:925-31. 2009
    ..These results suggest that let-7 plays an important role in adipocyte differentiation and that it does so in part by targeting HMGA2, thereby regulating the transition from clonal expansion to terminal differentiation...
  43. pmc Synthesis and activity of dafachronic acid ligands for the C. elegans DAF-12 nuclear hormone receptor
    Kamalesh K Sharma
    Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Mol Endocrinol 23:640-8. 2009
    ..Potency derives more from the A/B-ring configuration than from the stereochemistry at C-25...
  44. pmc Nuclear receptors of the enteric tract: guarding the frontier
    Daniel R Schmidt
    The Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9050, USA
    Nutr Rev 66:S88-97. 2008
    ..The major homeostatic functions of the enteric nuclear receptor network are the topic of this review...
  45. ncbi request reprint A Nuclear Receptor Atlas: 3T3-L1 adipogenesis
    Mingui Fu
    Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, Texas 75390 9050, USA
    Mol Endocrinol 19:2437-50. 2005
    ....
  46. pmc The starvation hormone, fibroblast growth factor-21, extends lifespan in mice
    Yuan Zhang
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    elife 1:e00065. 2012
    ..These findings raise the possibility that FGF21 can be used to extend lifespan in other species.DOI:http://dx.doi.org/10.7554/eLife.00065.001...
  47. pmc Sterol-dependent nuclear import of ORP1S promotes LXR regulated trans-activation of apoE
    Sungsoo Lee
    Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9039, United States
    Exp Cell Res 318:2128-42. 2012
    ..1 and ME.2 enhancer elements of the apoE gene. We propose that ORP1S is a cytoplasmic sterol sensor, which transports sterols to the nucleus and promotes LXR-dependent gene transcription through select enhancer elements...
  48. pmc Endocrine fibroblast growth factors 15/19 and 21: from feast to famine
    Matthew J Potthoff
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, 75390, USA
    Genes Dev 26:312-24. 2012
    ..FGF21 also acts in an autocrine fashion in several tissues, including adipose. The pharmacological actions of FGF15/19 and FGF21 make them attractive drug candidates for treating metabolic disease...
  49. ncbi request reprint Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans
    Daniel L Motola
    Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Cell 124:1209-23. 2006
    ....
  50. ncbi request reprint Retinoid x receptor heterodimers in the metabolic syndrome
    Andrew I Shulman
    Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75390, USA
    N Engl J Med 353:604-15. 2005
  51. pmc Partial resistance to peroxisome proliferator-activated receptor-alpha agonists in ZDF rats is associated with defective hepatic mitochondrial metabolism
    Santhosh Satapati
    The Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Diabetes 57:2012-21. 2008
    ..The purpose of this study is to determine whether abnormal mitochondrial metabolism plays a role in the dysregulation of both hepatic fat and glucose metabolism during diabetes...
  52. ncbi request reprint Identification of a liver-specific uridine phosphorylase that is regulated by multiple lipid-sensing nuclear receptors
    Yuan Zhang
    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9050, USA
    Mol Endocrinol 18:851-62. 2004
    ....
  53. ncbi request reprint The Drosophila orphan nuclear receptor DHR38 mediates an atypical ecdysteroid signaling pathway
    Keith D Baker
    Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Cell 113:731-42. 2003
    ..Taken together, these data reveal the existence of a separate structural class of nuclear receptors that is conserved from fly to humans...
  54. pmc Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase
    Jeffrey B Cheng
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 101:7711-5. 2004
    ..These data identify CYP2R1 as a biologically relevant vitamin D 25-hydroxylase and reveal the molecular basis of a human genetic disease, selective 25-hydroxyvitamin D deficiency...
  55. ncbi request reprint Expression of LRH-1 and SF-1 in the mouse ovary: localization in different cell types correlates with differing function
    Margaret M Hinshelwood
    Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390 9038, USA
    Mol Cell Endocrinol 207:39-45. 2003
    ..Based on these findings, we propose that LRH-1 plays an important role as a competence factor in regulating aromatase, and thus estrogen biosynthesis, in ovary...
  56. doi request reprint High-throughput real-time quantitative reverse transcription PCR
    Angie L Bookout
    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Curr Protoc Mol Biol . 2006
    ..This protocol describes the production and quantitation of synthetic RNA molecules for real-time and non-real-time RT-PCR applications...
  57. pmc Nuclear receptor regulation of stemness and stem cell differentiation
    Yangsik Jeong
    Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Texas 75390, USA
    Exp Mol Med 41:525-37. 2009
    ..These studies provide insights into the therapeutic potential of the NR superfamily in stem cell therapy and in treating stem cell-associated diseases (e.g., cancer stem cell)...
  58. ncbi request reprint Liver X receptor signaling pathways in cardiovascular disease
    Peter Tontonoz
    Howard Hughes Medical Institute, University of California, Los Angeles School of Medicine, Box 951662, Los Angeles, California 90095 1662, USA
    Mol Endocrinol 17:985-93. 2003
    ..These observations identify the LXR pathway as a potential target for therapeutic intervention in human cardiovascular disease...
  59. pmc Nuclear receptor expression defines a set of prognostic biomarkers for lung cancer
    Yangsik Jeong
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
    PLoS Med 7:e1000378. 2010
    ....
  60. pmc PPARγ in vagal neurons regulates high-fat diet induced thermogenesis
    Chen Liu
    Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
    Cell Metab 19:722-30. 2014
    ..Collectively, our findings provide insights into how vagal afferents survey peripheral metabolic cues and suggest that the reduction of PPARγ in NG neurons may serve as a protective mechanism against diet-induced weight gain. ..
  61. ncbi request reprint Vitamin D receptor as an intestinal bile acid sensor
    Makoto Makishima
    Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9050, USA
    Science 296:1313-6. 2002
    ..These studies offer a mechanism that may explain the proposed protective effects of vitamin D and its receptor against colon cancer...
  62. ncbi request reprint The liver X receptor gene team: potential new players in atherosclerosis
    Joyce J Repa
    Department of Physiology, Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Nat Med 8:1243-8. 2002
  63. ncbi request reprint De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase
    Jeffrey B Cheng
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75390, USA
    J Biol Chem 278:38084-93. 2003
    ..CYP2R1 mRNA is abundant in the liver and testis, and present at lower levels in other tissues. The data suggest that CYP2R1 is a strong candidate for the microsomal vitamin D 25-hydroxylase...
  64. ncbi request reprint Reciprocal regulation of inflammation and lipid metabolism by liver X receptors
    Sean B Joseph
    Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California, USA
    Nat Med 9:213-9. 2003
    ..These findings identify LXRs as lipid-dependent regulators of inflammatory gene expression that may serve to link lipid metabolism and immune functions in macrophages...

Research Grants6

  1. Conference on Nuclear Receptor Superfamily
    David Mangelsdorf; Fiscal Year: 2002
    ....
  2. Nuclear Receptors: Orphan Brothers
    David Mangelsdorf; Fiscal Year: 2004
    ....
  3. MECHANISMS OF DRUG ACTION AND DISPOSITION
    David Mangelsdorf; Fiscal Year: 2007
    ..This program seeks to train the next generation of scientists who will make these discoveries and insure that scientific research on human health remains vibrant and at the cutting edge. ..