Role of Eicosanoids in Renal Function

Summary

Principal Investigator: NANCY JOAN BROWN
Abstract: The kidney plays a key role in the control of body fluid volume and composition, and tubular and/or hemodynamic dysfunction are common features of diseases such as hypertension and diabetes. The renal P450 arachidonic acid (AA) monooxygenase biosynthesizes hydroxy- and epoxy-AA derivatives that are known to modulate tubular transport and vascular reactivity. Animal models of P450 gene dysfunction confirmed the physiological importance of these enzymes, characterized their pathophysiological roles, and provided insights into the mechanism of action of their metabolites. Studies of the pathophysiological roles of human P450s identified associations between P450 gene variants with hypertension, the progression of renal disease, and with components of metabolic syndrome. This application proposes to build upon these studies and to address: a) mechanisms by which the P450-eicosanoids regulate renal tubular transport and vascular reactivity, b) the role of P450s in human hypertension and renal complications of diabetes, and c) the molecular basis of these pathophysiological roles. To achieve these goals, we developed a multidisciplinary approach for studies of P450-isoform specific phenotypes at the cellular, organ and whole animal levels, the analysis of associations between alterations in human P450 gene structure/expression and disease, and for clinical studies of their metabolic and functional consequences. Cyp2c and Cyp4a knockout mice will be used to study gene-dependent changes in: a) renal EET and/or 20-HETE synthase expression, b) tubular transport and/or vascular reactivity, and c) systemic blood pressure and the progression of renal disease. Associations between CYP2C8/2C9 or CYP4A11 genotypes with blood pressure, insulin sensitivity, and urine and plasma EET and 20-HETE levels will be explored to define pathophysiological correlations between variant alleles, AA epoxidation/hydroxylation, and individual responses to changes in dietary salt intake, the administration of diuretics, or peroxisomal proliferator activated receptor (alpha) ligands. Our long term goals are to provide a molecular understanding of role(s) of P450 eicosanoids in renal physiological, their mechanism and site of action, and relevance to human disease. These are needed for the development of meaningful approaches for: a) the unequivocal definition of human pathophysiological significance, and b) future pharmacological targeting, and clinical diagnosis and intervention.
Funding Period: 1997-07-01 - 2014-06-30
more information: NIH RePORT

Top Publications

  1. pmc Epoxyeicosatrienoic acid agonist regulates human mesenchymal stem cell-derived adipocytes through activation of HO-1-pAKT signaling and a decrease in PPARγ
    Dong Hyun Kim
    Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, Ohio 43614, USA
    Stem Cells Dev 19:1863-73. 2010
  2. pmc Soluble epoxide hydrolase contamination of specific catalase preparations inhibits epoxyeicosatrienoic acid vasodilation of rat renal arterioles
    Kathryn M Gauthier
    Department of Pharmacology and Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Am J Physiol Renal Physiol 301:F765-72. 2011
  3. pmc CYP4A11 T8590C polymorphism, salt-sensitive hypertension, and renal blood flow
    Jonathan S Williams
    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    J Hypertens 29:1913-8. 2011
  4. pmc CYP4A11 variant is associated with high-density lipoprotein cholesterol in women
    C C White
    Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
    Pharmacogenomics J 13:44-51. 2013
  5. pmc Cyclooxygenases and lipoxygenases in cancer
    Claus Schneider
    Department of Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232, USA
    Cancer Metastasis Rev 30:277-94. 2011
  6. pmc EET signaling in cancer
    Dipak Panigrahy
    Vascular Biology Program, Boston Children s Hospital, Division of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Cancer Metastasis Rev 30:525-40. 2011
  7. pmc EGFR signaling promotes TGFβ-dependent renal fibrosis
    Jianchun Chen
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Am Soc Nephrol 23:215-24. 2012
  8. pmc Proteomic analysis of urine exosomes by multidimensional protein identification technology (MudPIT)
    Zhen Wang
    Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA
    Proteomics 12:329-38. 2012
  9. pmc Intrarenal dopamine modulates progressive angiotensin II-mediated renal injury
    Shilin Yang
    Nashville Veterans Affairs Hospital and Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Am J Physiol Renal Physiol 302:F742-9. 2012
  10. pmc Angiotensin II induces epithelial-to-mesenchymal transition in renal epithelial cells through reactive oxygen species/Src/caveolin-mediated activation of an epidermal growth factor receptor-extracellular signal-regulated kinase signaling pathway
    Jianchun Chen
    Departments of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Mol Cell Biol 32:981-91. 2012

Research Grants

  1. Regulatory Mechanisms In Intestinal Motility
    Kenton M Sanders; Fiscal Year: 2013
  2. INTESTINAL IMMUNE SYSTEM IN HOST-ENVIRONMENT INTERACTION
    MARTIN FREDERICK KAGNOFF; Fiscal Year: 2013
  3. Rocky Mountain Regional Center of Excellence or Biodefense and Emerging Infectiou
    John T Belisle; Fiscal Year: 2013
  4. Northeast Biodefense Center
    W Ian Lipkin; Fiscal Year: 2013
  5. HORMONAL REGULATION OF BLOOD PRESSURE
    Michal Laniado Schwartzman; Fiscal Year: 2013
  6. IPF Fibroblast Phenotype
    Craig A Henke; Fiscal Year: 2013
  7. UNMC EPPLEY CANCER CENTER SUPPORT GRANT
    Kenneth H Cowan; Fiscal Year: 2013

Detail Information

Publications147 found, 100 shown here

  1. pmc Epoxyeicosatrienoic acid agonist regulates human mesenchymal stem cell-derived adipocytes through activation of HO-1-pAKT signaling and a decrease in PPARγ
    Dong Hyun Kim
    Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, Ohio 43614, USA
    Stem Cells Dev 19:1863-73. 2010
    ..These novel observations highlight the seminal role of arachidonic acid metabolism in MSCs and suggest that an EET agonist may have potential therapeutic use in the treatment of dyslipidemia, diabetes, and the metabolic syndrome...
  2. pmc Soluble epoxide hydrolase contamination of specific catalase preparations inhibits epoxyeicosatrienoic acid vasodilation of rat renal arterioles
    Kathryn M Gauthier
    Department of Pharmacology and Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Am J Physiol Renal Physiol 301:F765-72. 2011
    ..However, some commercial catalase preparations are contaminated with sEH, and these contaminated preparations diminish the biological activity of H(2)O(2) and EETs...
  3. pmc CYP4A11 T8590C polymorphism, salt-sensitive hypertension, and renal blood flow
    Jonathan S Williams
    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    J Hypertens 29:1913-8. 2011
    ..We tested the hypothesis that CYP4A11 T8590C genotype is associated with salt sensitivity in the International Hypertensive Pathotype cohort...
  4. pmc CYP4A11 variant is associated with high-density lipoprotein cholesterol in women
    C C White
    Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
    Pharmacogenomics J 13:44-51. 2013
    ..02-1.90), P=0.04). In the BioVU cohort, the CYP4A11 8590C allele was also associated with low HDL-C in women (odds ratio 1.69 (95% CI 1.03-2.77, P=0.04)). There was no relationship between genotype and HDL-C in men in either cohort...
  5. pmc Cyclooxygenases and lipoxygenases in cancer
    Claus Schneider
    Department of Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232, USA
    Cancer Metastasis Rev 30:277-94. 2011
    ....
  6. pmc EET signaling in cancer
    Dipak Panigrahy
    Vascular Biology Program, Boston Children s Hospital, Division of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Cancer Metastasis Rev 30:525-40. 2011
    ..In this review, the emerging role of EET signaling in angiogenesis, inflammation, and cancer is discussed...
  7. pmc EGFR signaling promotes TGFβ-dependent renal fibrosis
    Jianchun Chen
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Am Soc Nephrol 23:215-24. 2012
    ....
  8. pmc Proteomic analysis of urine exosomes by multidimensional protein identification technology (MudPIT)
    Zhen Wang
    Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA
    Proteomics 12:329-38. 2012
    ....
  9. pmc Intrarenal dopamine modulates progressive angiotensin II-mediated renal injury
    Shilin Yang
    Nashville Veterans Affairs Hospital and Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Am J Physiol Renal Physiol 302:F742-9. 2012
    ..In contrast, their expression was markedly attenuated in COMT KO mice. These results demonstrate a role for intrarenal dopamine to buffer the detrimental effects of ANG II upon the kidney...
  10. pmc Angiotensin II induces epithelial-to-mesenchymal transition in renal epithelial cells through reactive oxygen species/Src/caveolin-mediated activation of an epidermal growth factor receptor-extracellular signal-regulated kinase signaling pathway
    Jianchun Chen
    Departments of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Mol Cell Biol 32:981-91. 2012
    ....
  11. pmc Epoxides and soluble epoxide hydrolase in cardiovascular physiology
    John D Imig
    Department of Pharmacology and Toxicology, Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
    Physiol Rev 92:101-30. 2012
    ..Given the impact of EETs to cardiovascular physiology, there is emerging evidence that development of EET-based therapeutics will be beneficial for cardiovascular diseases...
  12. pmc Inhibition of soluble epoxide hydrolase by cis-4-[4-(3-adamantan-1-ylureido)cyclohexyl-oxy]benzoic acid exhibits antihypertensive and cardioprotective actions in transgenic rats with angiotensin II-dependent hypertension
    Jan Neckar
    Department of Developmental Cardiology, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Clin Sci (Lond) 122:513-25. 2012
    ..These findings indicate that chronic inhibition of sEH exhibits antihypertensive and cardioprotective actions in this transgenic model of angiotensin II-dependent hypertension...
  13. pmc Dopamine, the kidney, and hypertension
    Raymond C Harris
    Division of Nephrology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Curr Hypertens Rep 14:138-43. 2012
    ....
  14. pmc Captopril attenuates hypertension and renal injury induced by the vascular endothelial growth factor inhibitor sorafenib
    Tasuku Nagasawa
    Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Clin Exp Pharmacol Physiol 39:454-61. 2012
    ..These findings indicate that captopril treatment, in addition to alleviating the detrimental side-effect of hypertension, decreases the renal injury associated with anticancer VEGFi therapies such as sorafenib...
  15. pmc Lysine-specific demethylase 1: an epigenetic regulator of salt-sensitive hypertension
    Jonathan S Williams
    Division of Endocrinology, Diabetes and Hypertension, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Am J Hypertens 25:812-7. 2012
    ..The aim of this study was to test the hypothesis that dietary salt influences the activity of a histone-modifying enzyme, lysine-specific demethylase 1 (LSD-1), which in turn is associated with salt-sensitivity of blood pressure (BP)...
  16. pmc Polymorphisms in the serum- and glucocorticoid-inducible kinase 1 gene are associated with blood pressure and renin response to dietary salt intake
    A D Rao
    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Hum Hypertens 27:176-80. 2013
    ..SGK1 genetic variants are associated with salt sensitivity of BP and PRA in human hypertension. Genotype status at these SGK1 variants may identify individuals prone to salt-sensitive hypertension...
  17. pmc Polymorphisms in the transcription factor NRF2 and forearm vasodilator responses in humans
    Ewa D Marczak
    Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA
    Pharmacogenet Genomics 22:620-8. 2012
    ..As NRF2 is a key transcription factor in antioxidant defense, we aimed to determine whether polymorphisms within the promoter region of the gene encoding NRF2 (NFE2L2) would significantly modify vasodilator responses in humans...
  18. pmc Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice
    Ming Zhi Zhang
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Clin Invest 121:2845-54. 2011
    ..Decreasing intrarenal dopamine subjects the kidney to unbuffered responses to Ang II and results in the development of hypertension and a dramatic decrease in longevity...
  19. pmc 17(R),18(S)-epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: structure-activity relationships and stable analogues
    John R Falck
    Department of Biochemistry, University of Texas Southwestern, Dallas, Texas 75390, United States
    J Med Chem 54:4109-18. 2011
    ..Compared with natural material, the agonist and antagonist analogues are chemically and metabolically more robust and several show promise as templates for future development of clinical candidates...
  20. pmc Targeting epoxides for organ damage in hypertension
    John D Imig
    Department of Pharmacology and Toxicology, Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    J Cardiovasc Pharmacol 56:329-35. 2010
    ..These experimental findings provide evidence for sEH inhibitors and EET agonists as a therapeutic approach for cardiovascular diseases, hypertension, and the associated end-organ damage...
  21. pmc The glomerulus--a view from the outside--the podocyte
    Huifang Cheng
    Division of Nephrology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 2372, USA
    Int J Biochem Cell Biol 42:1380-7. 2010
    ..However, recent research in rodents has provided suggestive evidence for podocyte regeneration resulting from differentiation of progenitor cells within Bowman's capsule...
  22. pmc Enhanced pressor response to acute Ang II infusion in mice lacking membrane-associated prostaglandin E2 synthase-1
    Dong juan Zhang
    Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
    Acta Pharmacol Sin 31:1284-92. 2010
    ..To examine the contribution of vascular membrane-associated prostaglandin E2 synthase-1 (mPGES-1) to acute blood pressure homeostasis...
  23. pmc Modulation by cytochrome P450-4A ω-hydroxylase enzymes of adrenergic vasoconstriction and response to reduced PO₂ in mesenteric resistance arteries of Dahl salt-sensitive rats
    Gábor Raffai
    Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Microcirculation 17:525-35. 2010
    ..This study evaluated the contribution of the 20-HETE/cytochrome P450-4A ω-hydroxylase (CYP4A) system to the early development of salt-induced vascular changes in Dahl salt-sensitive (SS) rats...
  24. pmc Renal mechanisms contributing to the antihypertensive action of soluble epoxide hydrolase inhibition in Ren-2 transgenic rats with inducible hypertension
    Zuzana Honetschlägerová
    Department of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    J Physiol 589:207-19. 2011
    ..These data suggest that the oral administration of c-AUCB displays antihypertensive effects in Ren-2 transgenic rats with inducible malignant hypertension via an improvement of renal function...
  25. pmc Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with forearm vasodilator responses in humans
    Craig R Lee
    Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599 7569, USA
    Hypertension 57:116-22. 2011
    ....
  26. pmc Pd-catalyzed cross-coupling of α-(acyloxy)-tri-n-butylstannanes with alkenyl, aryl, and heteroaryl electrophiles
    Mohan Goli
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Org Lett 13:344-6. 2011
    ..Cross-couplings proceed with retention of configuration at the alkenyl and stannyl-substituted stereocenters...
  27. pmc N-acylsulfonamide assisted tandem C-H olefination/annulation: synthesis of isoindolinones
    Chen Zhu
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Org Lett 13:1214-7. 2011
    ..This transformation is compatible with aliphatic alkenes as well as conjugated alkenes. Notably, molecular oxygen can be used as the sole, eco-friendly oxidant...
  28. pmc Cytochrome P450 eicosanoids and cerebral vascular function
    John D Imig
    Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Expert Rev Mol Med 13:e7. 2011
    ..Thus, the CYP eicosanoids are key regulators of cerebral vascular function and novel therapeutic targets for cardiovascular diseases and neurological disorders...
  29. pmc Increases in plasma trans-EETs and blood pressure reduction in spontaneously hypertensive rats
    Houli Jiang
    Dept of Pharmacology, New York Medical College, 15 Dana Road, Valhalla, NY 10595, USA
    Am J Physiol Heart Circ Physiol 300:H1990-6. 2011
    ..In summary, inhibition of sEH resulted in a twofold increase in plasma trans-EETs and reduced mean BP in the SHR. The greater vasodilator potency of trans- vs. cis-EETs may contribute to the antihypertensive effects of sEH inhibitors...
  30. pmc CYP3A4 mediates growth of estrogen receptor-positive breast cancer cells in part by inducing nuclear translocation of phospho-Stat3 through biosynthesis of (±)-14,15-epoxyeicosatrienoic acid (EET)
    Ranjana Mitra
    From the Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Biol Chem 286:17543-59. 2011
    ..Furthermore, these studies indicate an essential role for Stat3 as a mediator of epoxygenase activity in breast cancer...
  31. pmc Role of cytochrome P-450 metabolites in the regulation of renal function and blood pressure in 2-kidney 1-clip hypertensive rats
    Alexandra Sporkova
    Department of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    Am J Physiol Regul Integr Comp Physiol 300:R1468-75. 2011
    ..While HET-0016 enhanced RBF, its anti-natriuretic effect likely prevented it from producing a blood pressure-lowering effect in the 2K1C model...
  32. pmc Telmisartan provides better renal protection than valsartan in a rat model of metabolic syndrome
    Abdul Hye Khan
    Department of Pharmacology and Toxicology and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
    Am J Hypertens 24:816-21. 2011
    ..We hypothesized that in cardiometabolic syndrome, telmisartan an ARB with peroxisome proliferators activated receptor-γ (PPAR-γ) activity will offer better renal protection...
  33. pmc Development of epoxyeicosatrienoic acid analogs with in vivo anti-hypertensive actions
    John D Imig
    Department of Pharmacology and Toxicology, Medical College of Wisconsin Milwaukee, WI, USA
    Front Physiol 1:157. 2010
    ....
  34. pmc Renin gene polymorphism: its relationship to hypertension, renin levels and vascular responses
    Bei Sun
    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Renin Angiotensin Aldosterone Syst 12:564-71. 2011
    ....
  35. pmc Tissue protection and endothelial cell signaling by 20-HETE analogs in intact ex vivo lung slices
    Elizabeth R Jacobs
    Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, United States
    Exp Cell Res 318:2143-52. 2012
    ..These methodologies create exciting possibilities for studying signaling by stable 20-HETE analogs and other factors in pulmonary endothelial and other lung cell types in their native milieu...
  36. pmc Intrarenal dopamine inhibits progression of diabetic nephropathy
    Ming Zhi Zhang
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Diabetes 61:2575-84. 2012
    ....
  37. pmc Different polymorphisms of the mineralocorticoid receptor gene are associated with either glucocorticoid or mineralocorticoid levels in hypertension
    Bei Sun
    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women s Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115, USA
    J Clin Endocrinol Metab 97:E1825-9. 2012
    ....
  38. pmc Anti-inflammatory effects of ω-3 polyunsaturated fatty acids and soluble epoxide hydrolase inhibitors in angiotensin-II-dependent hypertension
    Arzu Ulu
    Department of Entomology and UC Davis Comprehensive Cancer Center, University of California, Davis, CA, USA
    J Cardiovasc Pharmacol 62:285-97. 2013
    ....
  39. pmc Contribution of iNOS/sGC/PKG pathway, COX-2, CYP4A1, and gp91(phox) to the protective effect of 5,14-HEDGE, a 20-HETE mimetic, against vasodilation, hypotension, tachycardia, and inflammation in a rat model of septic shock
    Bahar Tunctan
    Department of Pharmacology, Faculty of Pharmacy, Mersin University, 33169 Mersin, Turkey
    Nitric Oxide 33:18-41. 2013
    ....
  40. pmc Immune and inflammatory role in renal disease
    John D Imig
    Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
    Compr Physiol 3:957-76. 2013
    ..An overview of common forms of acute and chronic renal disease is provided, followed by a discussion of common therapies that have anti-inflammatory or immunosuppressive effects in the treatment of renal disease...
  41. pmc Epithelial-specific deletion of 11β-HSD2 hinders Apcmin/+ mouse tumorigenesis
    Li Jiang
    Departments of Medicine and Cancer Biology, S 3206, MCN, Vanderbilt University Medical Center, Nashville, TN 37232
    Mol Cancer Res 11:1040-50. 2013
    ....
  42. ncbi Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer
    Ying Li
    Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071, China
    Toxicol Appl Pharmacol 272:37-48. 2013
    ..Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. ..
  43. pmc Low nitric oxide bioavailability upregulates renal heparin binding EGF-like growth factor expression
    Tomoki Miyazawa
    Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Kidney Int 84:1176-88. 2013
    ..Thus, our results suggest that decreased nitric oxide bioavailability leads to increased HB-EGF expression, which may be an important mediator of the resulting progressive diabetic nephropathy in eNOS-knockout diabetic mice. ..
  44. pmc 20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension
    Yan Ding
    1Department of Pharmacology, New York Medical College, 15 Dana Road, BSB Rm 530, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 305:F753-63. 2013
    ..This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels. ..
  45. pmc Orally active epoxyeicosatrienoic acid analog attenuates kidney injury in hypertensive Dahl salt-sensitive rat
    Md Abdul Hye Khan
    Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226
    Hypertension 62:905-13. 2013
    ....
  46. pmc Role of epoxyeicosatrienoic acids (EETs) in mediation of dopamine's effects in the kidney
    Ming Zhi Zhang
    Div of Nephrology, C3121 MCN, Vanderbilt Univ School of Medicine and Nashville Veterans Affairs Hospital, Nashville, TN 37232
    Am J Physiol Renal Physiol 305:F1680-6. 2013
    ..These studies demonstrate that renal EET levels are maintained by intrarenal dopamine, and Cyp2c44-derived EETs play an important role in intrarenal dopamine-induced natriuresis and diuresis. ..
  47. pmc PPARα activation can help prevent and treat non-small cell lung cancer
    Nataliya Skrypnyk
    Authors Affiliations Departments of Medicine, Division of Nephrology, Cancer Biology, and Biochemistry, Vanderbilt University Department of Medicine, Veterans Affairs Hospital, Nashville, Tennessee and Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas
    Cancer Res 74:621-31. 2014
    ....
  48. pmc Direct stereospecific synthesis of unprotected N-H and N-Me aziridines from olefins
    Jawahar L Jat
    Division of Chemistry, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Science 343:61-5. 2014
    ..Likewise, N-alkyl aziridines are prepared from N-alkylated DPH derivatives. Quantum-mechanical calculations suggest a plausible Rh-nitrene pathway. ..
  49. pmc 20-HETE regulates the angiogenic functions of human endothelial progenitor cells and contributes to angiogenesis in vivo
    Li Chen
    Department of Pharmacology, School of Medicine, Wuhan University, Wuhan, PR China L C, J Y, A M G Department of Pharmacology, New York Medical College, Valhalla, New York L C, R A, M S, K H G, M L S, A M G Department of Obstetrics and Gynecology, Westchester Medical Center, Valhalla, New York M K Obstetrics and Gynecology, Phelps Memorial Hospital Center, Sleepy Hollow, New York L G M University of Texas Southwestern Medical Center, Dallas, Texas J R F and Henry Ford Hospital, Detroit, Michigan A S A, A G S
    J Pharmacol Exp Ther 348:442-51. 2014
    ..These results strengthened the notion that 20-HETE regulates the angiogenic functions of EPC in vitro and EPC-mediated angiogenesis in vivo...
  50. pmc Epidermal growth factor, from gene organization to bedside
    Fenghua Zeng
    Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States
    Semin Cell Dev Biol 28:2-11. 2014
    ..In this review, we briefly describe the gene organization and tissue distribution of EGF, with emphasis on its biological and pathological roles in human diseases. ..
  51. pmc Androgen-sensitive hypertension associates with upregulated vascular CYP4A12-20-HETE synthase
    Cheng Chia Wu
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    J Am Soc Nephrol 24:1288-96. 2013
    ..Taken together, these results suggest that 20-HETE both mediates androgen-induced hypertension and can cause hypertension independent of androgen. ..
  52. pmc Novel orally active epoxyeicosatrienoic acid (EET) analogs attenuate cisplatin nephrotoxicity
    Md Abdul Hye Khan
    Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, Wisconsin 53226, USA
    FASEB J 27:2946-56. 2013
    ..Collectively, our data provide evidence that EET analogs attenuate cisplatin-induced nephrotoxicity by reducing oxidative stress, inflammation, ER stress, and apoptosis without affecting the chemotherapeutic effects of cisplatin...
  53. pmc Induction of angiotensin-converting enzyme and activation of the renin-angiotensin system contribute to 20-hydroxyeicosatetraenoic acid-mediated endothelial dysfunction
    Jennifer Cheng
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Arterioscler Thromb Vasc Biol 32:1917-24. 2012
    ....
  54. pmc Introgression of Brown Norway CYP4A genes on to the Dahl salt-sensitive background restores vascular function in SS-5(BN) consomic rats
    Kathleen M Lukaszewicz
    Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Clin Sci (Lond) 124:333-42. 2013
    ..These findings indicate that SS rats have an up-regulation of the CYP4A/20-HETE pathway resulting in elevated ROS (reactive oxygen species) and reduced NO bioavailability causing vascular dysfunction...
  55. pmc Soluble epoxide hydrolase inhibition exhibits antihypertensive actions independently of nitric oxide in mice with renovascular hypertension
    Libor Kopkan
    Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    Kidney Blood Press Res 35:595-607. 2012
    ..The present study was performed to examine whether the blood pressure (BP)-lowering effects of soluble epoxide hydrolase (sEH) inhibition in two-kidney, one-clip (2K1C) Goldblatt hypertension are nitric oxide (NO) dependent...
  56. pmc NS-398 reverses hypotension in endotoxemic rats: contribution of eicosanoids, NO, and peroxynitrite
    Bahar Tunctan
    Department of Pharmacology, Faculty of Pharmacy, Mersin University, Mersin, Turkey
    Prostaglandins Other Lipid Mediat 104:93-108. 2013
    ..Taken together, we concluded that an increase in 20-HETE levels associated with a decrease in the production of vasodilator prostanoids and NO participates in the effect of NS-398 to prevent hypotension in the rat model of septic shock...
  57. ncbi A novel treatment strategy for sepsis and septic shock based on the interactions between prostanoids, nitric oxide, and 20-hydroxyeicosatetraenoic acid
    Bahar Tunctan
    Department of Pharmacology, Yenisehir Campus, Mersin University, Mersin, Turkey
    Antiinflamm Antiallergy Agents Med Chem 11:121-50. 2012
    ....
  58. pmc Antihypertensive action of soluble epoxide hydrolase inhibition in Ren-2 transgenic rats is mediated by suppression of the intrarenal renin-angiotensin system
    Sárka Varcabová
    Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    Clin Exp Pharmacol Physiol 40:273-81. 2013
    ..Together, the data indicate that the antihypertensive actions of sEH inhibition in TGR are predominantly mediated via significant suppression of intrarenal renin-angiotensin system activity...
  59. pmc CSF-1 signaling mediates recovery from acute kidney injury
    Ming Zhi Zhang
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Clin Invest 122:4519-32. 2012
    ..These findings demonstrated that CSF-1-mediated expansion and polarization of resident renal macrophages/dendritic cells is an important mechanism mediating renal tubule epithelial regeneration after AKI...
  60. pmc Epoxyeicosatrienoic acids (EETs) regulate epithelial sodium channel activity by extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated phosphorylation
    Nataliya Pidkovka
    Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 288:5223-31. 2013
    ....
  61. pmc mVps34 deletion in podocytes causes glomerulosclerosis by disrupting intracellular vesicle trafficking
    Jianchun Chen
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    J Am Soc Nephrol 24:198-207. 2013
    ..In conclusion, these results demonstrate an indispensable role for mVps34 in the trafficking of intracellular vesicles to protect the normal cellular metabolism, structure, and function of podocytes...
  62. pmc Cyclooxygenase-2 dependent metabolism of 20-HETE increases adiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes
    Dong Hyun Kim
    Joan C Edwards School of Medicine, Marshall University, Huntington, WV, USA
    J Lipid Res 54:786-93. 2013
    ..Taken together we show for the first time that 20-HETE-derived COX-2-dependent 20-OH-PGE₂ enhances mature inflamed adipocyte hypertrophy in MSC undergoing adipogenic differentiation...
  63. pmc Antihypertensive and renoprotective actions of soluble epoxide hydrolase inhibition in ANG II-dependent malignant hypertension are abolished by pretreatment with L-NAME
    Zuzana Honetschlägerová
    Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    J Hypertens 31:321-32. 2013
    ..The present study was performed to investigate in a model of malignant hypertension if the antihypertensive actions of soluble epoxide hydrolase (sEH) inhibition are nitric oxide (NO)-dependent...
  64. pmc Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice
    P Luo
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, 2200 Pierce Avenue, 560 RRB, Nashville, TN 37232 6602, USA
    Diabetologia 56:901-10. 2013
    ..We hypothesised that elimination of endogenous aldosterone would prevent obesity-induced insulin resistance and hyperglycaemia...
  65. pmc Epoxyeicosatrienoic acids, 20-hydroxyeicosatetraenoic acid, and renal microvascular function
    John D Imig
    Department of Pharmacology and Toxicology, Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Prostaglandins Other Lipid Mediat 104:2-7. 2013
    ..These findings have demonstrated the important contributions that 20-HETE and EETs play in the regulation of renal microvascular function. ..
  66. pmc Soluble epoxide hydrolase inhibition and peroxisome proliferator activated receptor γ agonist improve vascular function and decrease renal injury in hypertensive obese rats
    John D Imig
    Department of Pharmacology and Toxicology and Cardiovascular Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Exp Biol Med (Maywood) 237:1402-12. 2012
    ..These results indicate that even though sEHi or PPARγ agonist have benefits when used individually, the combination is more beneficial for the multidisease features in cardiometabolic syndrome...
  67. pmc Fenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension
    Kimberly Gilbert
    Department of Medicine, Vanderbilt School of Medicine, Nashville, Tennessee, USA
    J Hypertens 31:820-9. 2013
    ..We tested the hypothesis that the effect of fenofibrate on blood pressure depends on salt sensitivity...
  68. pmc Identification of endogenous substrates of orphan cytochrome P450 enzymes through the use of untargeted metabolomics approaches
    Qian Cheng
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN, USA
    Methods Mol Biol 987:71-7. 2013
    ..those whose endogenous substrates are not known. Here we describe a high-performance liquid chromatography-coupled mass spectrometry (HPLC-MS)-based metabolomics approach to identify an endogenous substrate of an orphan cytochrome P450...
  69. ncbi Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice
    Fenghua Zeng
    Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Kidney Int 86:538-47. 2014
    ..These studies suggest that the high level of ErbB4 expression seen in cpk mice may exert relative cytoprotective effects in renal epithelia. ..
  70. pmc Enantioselective, organocatalytic reduction of ketones using bifunctional thiourea-amine catalysts
    De Run Li
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Org Lett 12:1756-9. 2010
    ..The hydride in the complex is endowed with enhanced nucleophilicity while the thiourea concomitantly embraces and activates the carbonyl...
  71. ncbi 14,15-Dihydroxyeicosatrienoic acid activates peroxisome proliferator-activated receptor-alpha
    Xiang Fang
    Dept of Biochemistry, Univ of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
    Am J Physiol Heart Circ Physiol 290:H55-63. 2006
    ..These findings suggest that 14,15-DHET, produced from 14,15-EET by the action of SEH, may function as an endogenous activator of PPARalpha...
  72. pmc Preparation of N-tBoc L-glutathione dimethyl and di-tert-butyl esters: versatile synthetic building blocks
    J R Falck
    Departments of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9038, USA
    Bioorg Med Chem 15:1062-6. 2007
    ..These l-glutathione derivatives are versatile synthetic building blocks for the preparation of S-glutathione adducts...
  73. ncbi Physiology of electrogenic SLC26 paralogues
    Michael F Romero
    Physiology and Biophysics, Case Western Reserve University, School of Medicine, Cleveland, OH 44106 4970, USA
    Novartis Found Symp 273:126-38; discussion 138-47, 261-4. 2006
    ..Our experiments and those of others continue to reveal additional characteristics and unique roles for this new class of electrogenic anion transporters...
  74. ncbi Epoxyeicosatrienoic Acid inhibition alters renal hemodynamics during pregnancy
    Hui Huang
    Department of Physiology, Medical College of Georgia, Augusta, GA 30912, USA
    Exp Biol Med (Maywood) 231:1744-52. 2006
    ..These results suggest that upregulation of renal vascular and tubular EETs contributes to the control of blood pressure and renal function during pregnancy...
  75. ncbi 20-carboxy-arachidonic acid is a dual activator of peroxisome proliferator-activated receptors alpha and gamma
    Xiang Fang
    Department of Biochemistry, 4 403 BSB, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
    Prostaglandins Other Lipid Mediat 82:175-84. 2007
    ..87+/-0.12 microM) and PPARgamma (Kd=1.7+/-0.5 microM). These findings suggest that 20-COOH-AA, a relatively stable metabolite of 20-HETE, might function as an endogenous dual activator of PPARalpha and PPARgamma...
  76. ncbi Chromium-carbyne complexes: intermediates for organic synthesis
    Romain Bejot
    Laboratoire de Synthese Bio Organique, UMR 7175 LC1, Faculte de Pharmacie, Universite Louis Pasteur de Strasbourg, 74 route du Rhin, BP 24, 67 401 Illkirch, France
    Angew Chem Int Ed Engl 46:1719-22. 2007
  77. pmc Stereospecific cross-coupling of alpha-(thiocarbamoyl)organostannanes with alkenyl, aryl, and heteroaryl iodides
    J R Falck
    Departments of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Am Chem Soc 129:790-3. 2007
    ..Cross-couplings proceed with retention of configuration at the alkenyl- and stannyl-substituted stereocenters...
  78. ncbi Protein phosphatase 2A and Ca2+-activated K+ channels contribute to 11,12-epoxyeicosatrienoic acid analog mediated mesenteric arterial relaxation
    Christiana Dimitropoulou
    Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA, USA
    Prostaglandins Other Lipid Mediat 83:50-61. 2007
    ..These findings provide initial evidence that PP2A activity contributes to 11,12-EET and 11,12-EET analog activation of mesenteric resistant artery BK(Ca) channels and vasorelaxation...
  79. pmc Mitogenic activity and signaling mechanism of 2-(14,15- epoxyeicosatrienoyl)glycerol, a novel cytochrome p450 arachidonate metabolite
    Jianchun Chen
    C 3121 Medical Center North, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Mol Cell Biol 27:3023-34. 2007
    ....
  80. pmc Epoxygenase eicosanoids: synthesis of tetrahydrofuran-diol metabolites and their vasoactivity
    J R Falck
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Bioorg Med Chem Lett 17:2634-8. 2007
    ..The THFDs potently induced relaxation of pre-contracted bovine arteries...
  81. ncbi Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis
    Ambra Pozzi
    Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Biol Chem 282:17685-95. 2007
    ....
  82. ncbi Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats
    Hui Huang
    Dept of Physiology, Medical College of Georgia, Augusta, GA 30912, USA
    Am J Physiol Renal Physiol 293:F342-9. 2007
    ....
  83. ncbi Synthesis and stereochemical assignment of FR252921, a promising immunosuppressant
    J Russell Falck
    Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9038, USA
    Angew Chem Int Ed Engl 46:4527-9. 2007
  84. ncbi Peroxisome proliferator activated receptor alpha/gamma dual agonist tesaglitazar attenuates diabetic nephropathy in db/db mice
    Dae Ryong Cha
    Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 2372, USA
    Diabetes 56:2036-45. 2007
    ..These findings support the utility of dual PPARalpha/gamma agonists in treating type 2 diabetes and diabetic nephropathy...
  85. ncbi Peroxisome proliferator-activated receptor-alpha deficiency protects aged mice from insulin resistance induced by high-fat diet
    Dae Ryong Cha
    Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn 37232 2372, USA
    Am J Nephrol 27:479-82. 2007
    ..The aim of this study was to evaluate the potential role of PPARalpha in insulin resistance in aging mice induced by a high-fat diet...
  86. pmc Antihypertensive effects of selective prostaglandin E2 receptor subtype 1 targeting
    Youfei Guan
    Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    J Clin Invest 117:2496-505. 2007
    ..Similarly, the pressor response to EP1-selective agonists sulprostone and 17-phenyltrinor PGE2 were blunted by SC51322 and in EP1-null mice. These data support the possibility of targeting the EP1 receptor for antihypertensive therapy...
  87. ncbi Expression of mouse membrane-associated prostaglandin E2 synthase-2 (mPGES-2) along the urogenital tract
    Guangrui Yang
    Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing 100083, China
    Biochim Biophys Acta 1761:1459-68. 2006
    ..This expression pattern is consistent with an important role for mPGES-2-mediated PGE(2) in urogenital function...
  88. pmc Fe(0)-mediated synthesis of tri- and tetra-substituted olefins from carbonyls: an environmentally friendly alternative to Cr(II)
    J R Falck
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Org Chem 71:8178-82. 2006
    ....
  89. ncbi Regulation of potassium channels in coronary smooth muscle by adenoviral expression of cytochrome P-450 epoxygenase
    William B Campbell
    Dept of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
    Am J Physiol Heart Circ Physiol 290:H64-71. 2006
    ..These studies indicate that 14(S),15(R)-EET is a sufficient endogenous activator of BK(Ca) channels in coronary SMCs...
  90. ncbi Liver X receptor agonist TO-901317 upregulates SCD1 expression in renal proximal straight tubule
    Yahua Zhang
    Division of Nephrology, S 3223 MCN, Vanderbilt Univ Medical Center, Nashville, TN 37232 2372, USA
    Am J Physiol Renal Physiol 290:F1065-73. 2006
    ..Taken together, these data suggest LXR activation of SCD1 expression may play an important role in regulating lipid metabolism and cell function in renal proximal straight tubules...
  91. ncbi Cytochrome P450 epoxygenases provide a novel mechanism for penile erection
    Liming Jin
    Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA
    FASEB J 20:539-41. 2006
    ..Inhibition of this pathway attenuated erectile function, suggesting that EETs are required for normal erection...
  92. ncbi Mechanism of rat mesenteric arterial KATP channel activation by 14,15-epoxyeicosatrienoic acid
    Dan Ye
    Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Am J Physiol Heart Circ Physiol 290:H1326-36. 2006
    ..These results suggest that 14,15-EET activates vascular K(ATP) channels through ADP-ribosylation of G(s)alpha...
  93. ncbi Accelerated diabetic nephropathy in mice lacking the peroxisome proliferator-activated receptor alpha
    Cheol Whee Park
    Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, 62, Yoido Dong, Youngdeungpo ku, Seoul, Korea 150 713
    Diabetes 55:885-93. 2006
    ..PPARalpha agonists may serve as useful therapeutic agents for type 1 diabetic nephropathy...
  94. ncbi Role of EGF receptor activation in angiotensin II-induced renal epithelial cell hypertrophy
    Jianchun Chen
    Department of Medicine, Vanderbilt University School of Medicine, and Department of Veterans Affairs, Nashville, TN 37232, USA
    J Am Soc Nephrol 17:1615-23. 2006
    ..In summary, this is the first demonstration that HB-EGF shedding-dependent EGFR transactivation, along with activation of TGF-beta signaling pathways, mediates Ang II-induced renal tubular epithelial cell hypertrophy...
  95. ncbi PPARalpha agonist fenofibrate improves diabetic nephropathy in db/db mice
    C W Park
    Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Kidney Int 69:1511-7. 2006
    ..The activation of PPARalpha by fenofibrate in mesangial cells may partially contribute to its renal protection. Thus, fenofibrate may serve as a therapeutic agent for type II diabetes and diabetic nephropathy...
  96. ncbi Increased renal vascular reactivity to ANG II after unilateral nephrectomy in the rat involves 20-HETE
    E Joly
    Service de Physiologie et Pharmacologie, Universite de Mons Hainaut, Belgium
    Am J Physiol Regul Integr Comp Physiol 291:R977-86. 2006
    ....

Research Grants30

  1. Regulatory Mechanisms In Intestinal Motility
    Kenton M Sanders; Fiscal Year: 2013
    ..The investigative team is highly synergistic and collaborative, and the PPG has a long track-record of productivity and novel discovery ..
  2. INTESTINAL IMMUNE SYSTEM IN HOST-ENVIRONMENT INTERACTION
    MARTIN FREDERICK KAGNOFF; Fiscal Year: 2013
    ..The research projects are supported by four Cores: a Mouse Model Core, a Histopathology Core, an Imaging and Cell Sorting Core and an Administrative Core. ..
  3. Rocky Mountain Regional Center of Excellence or Biodefense and Emerging Infectiou
    John T Belisle; Fiscal Year: 2013
    ..abstract_text> ..
  4. Northeast Biodefense Center
    W Ian Lipkin; Fiscal Year: 2013
    ..As a Center based in a School of Public Health and a State Department of Health, the NBC has a firm commitment to and practical understanding of Emergency Preparedness. ..
  5. HORMONAL REGULATION OF BLOOD PRESSURE
    Michal Laniado Schwartzman; Fiscal Year: 2013
    ..ular tone, in the pathophysiology of hypertension and cardiovascular disease. ..
  6. IPF Fibroblast Phenotype
    Craig A Henke; Fiscal Year: 2013
    ..A major objective of this Program Project is to inform decisions of the IPF Clinical Network by providing information that can be translated into novel therapeutic strategies for IPF. ..
  7. UNMC EPPLEY CANCER CENTER SUPPORT GRANT
    Kenneth H Cowan; Fiscal Year: 2013
    ....