Scholars

Manganiello, Vincent C., M.D., Ph.D.

Senior Investigator

Positions:

Senior Investigator, Laboratory of Biochemical Physiology

Research Areas:

General & Internal Medicine, Endocrinology & Metabolism, Science & Technology - Other Topics, Biochemistry & Molecular Biology, Dentistry, Oral Surgery & Medicine, Cardiovascular System & Cardiology, Biophysics, Pharmacology & Pharmacy, Respiratory System, Cell Biology, Hematology, Biotechnology & Applied Microbiology, Urology & Nephrology, Immunology

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overview

Vincent Manganiello earned his Ph.D. and M.D. from Johns Hopkins University in 1965 and 1967, respectively. He joined the NHLBI after his internship from 1967 to 1968 at the Harriet Lane Pediatric Service at Johns Hopkins Hospital. In 2010 he became a Senior Investigator and Chief of the Laboratory of Biochemical Physiology (CPB). A member of the NHLBI institutional review board, he also serves on the editorial boards of the Journal of Biological Chemistry and CHEST. Dr. Manganiello received the NIH Public Health Service Special Recognition Award in 1991, the NIH Director's Award in 1994, a NIH Bench to Bedside Award in 2003, and the Excellence in Sarcoidosis Research Award at the 2005 American Thoracic Society Meeting. He was admitted into the Johns Hopkins University Society of Scholars in 2012. He has authored or coauthored more than 220 papers and book chapters. He is also a member of the American Society of Molecular and Biological Chemists, American Thoracic Society, American Diabetes Association, and American College of Chest Physicians.

selected publications

Academic Articles215

(2019). Phosphodiesterase type 3A (PDE3A), but not type 3B (PDE3B), contributes to the adverse cardiac remodeling induced by pressure overload. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY. 132, 60-70.
(2018). A pathophysiological role of PDE3 in allergic airway inflammation. JCI Insight. 3(2),
(2017). Phosphodiesterase 3A: a new player in development of interstitial cells of Cajal and a prospective target in gastrointestinal stromal tumors (GIST). 8(25), 41026-41043.
(2017). SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A. BIOSCIENCE REPORTS. 37,
(2017). White to beige conversion in PDE3B KO adipose tissue through activation of AMPK signaling and mitochondrial function. Scientific Reports. 7,
(2016). Effects of heterologous expression of human cyclic nucleotide phosphodiesterase 3A (hPDE3A) on redox regulation in yeast. BIOCHEMICAL JOURNAL. 473, 4205-4225.
(2016). Modulation of Polycystic Kidney Disease Severity by Phosphodiesterase 1 and 3 Subfamilies. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY. 27(5), 1312-1320.
(2016). Phosphodiesterase 3B (PDE3B) regulates NLRP3 inflammasome in adipose tissue. Scientific Reports. 6,
(2015). Cyclic Nucleotide Phosphodiesterases: important signaling modulators and therapeutic targets. ORAL DISEASES. 21(1), E25-E50.
(2015). Heme Oxygenase-1 Regulation of Matrix Metalloproteinase-1 Expression Underlies Distinct Disease Profiles in Tuberculosis. JOURNAL OF IMMUNOLOGY. 195(6), 2763-2773.
(2015). Inactivation of NF-kappa B p65 (RelA) in Liver Improves Insulin Sensitivity and Inhibits cAMP/PKA Pathway. DIABETES. 64(10), 3355-3362.
(2015). Regulation of Sarcoplasmic Reticulum Ca2+ ATPase 2 (SERCA2) Activity by Phosphodiesterase 3A (PDE3A) in Human Myocardium PHOSPHORYLATION-DEPENDENT INTERACTION OF PDE3A1 WITH SERCA2. JOURNAL OF BIOLOGICAL CHEMISTRY. 290(11), 6763-6776.
(2015). Serum Apolipoprotein A-I and Large High-Density Lipoprotein Particles Are Positively Correlated with FEV1 in Atopic Asthma. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 191(9), 990-1000.
(2015). Targeted disruption of PDE3B, but not PDE3A, protects murine heart from ischemia/reperfusion injury. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 112(17), E2253-E2262.
(2015). The Role of PDE3B Phosphorylation in the Inhibition of Lipolysis by Insulin. MOLECULAR AND CELLULAR BIOLOGY. 35(16), 2752-2760.
(2015). Tuberous Sclerosis Complex 2 Loss of Heterozygosity in Patients with Lung Disease and Cancer. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 191(3), 352-355.
(2014). Advances in targeting cyclic nucleotide phosphodiesterases. NATURE REVIEWS DRUG DISCOVERY. 13(4), 290-314.
(2014). Clinical and Molecular Genetics of the Phosphodiesterases (PDEs). ENDOCRINE REVIEWS. 35(2), 195-233.
(2014). Role of phosphodiesterase 2 in growth and invasion of human malignant melanoma cells. CELLULAR SIGNALLING. 26(9), 1807-1817.
(2013). A Role for Phosphodiesterase 3B in Acquisition of Brown Fat Characteristics by White Adipose Tissue in Male Mice. ENDOCRINOLOGY. 154(9), 3152-3167.
(2013). Phosphodiesterase Type 3A Regulates Basal Myocardial Contractility Through Interacting With Sarcoplasmic Reticulum Calcium ATPase Type 2a Signaling Complexes in Mouse Heart. CIRCULATION RESEARCH. 112(2), 289-+.
(2013). Selective regulation of cyclic nucleotide phosphodiesterase PDE3A isoforms. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 110(49), 19778-19783.
(2012). Cyclic Nucleotide Phosphodiesterase 3 Signaling Complexes. HORMONE AND METABOLIC RESEARCH. 44(10), 776-785.
(2012). Regulation of the pro-inflammatory cytokine osteopontin by GIP in adipocytes - A role for the transcription factor NFAT and phosphodiesterase 3B. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 425(4), 812-817.
(2012). Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases. CELL. 148(3), 421-433.
(2012). Resveratrol as a calorie restriction mimetic: therapeutic implications. TRENDS IN CELL BIOLOGY. 22(10), 546-554.
(2011). Cyclic nucleotide phosphodiesterases: critical modulators of endocrine, metabolic, and cardiovascular function and appealing therapeutic targets. CURRENT OPINION IN PHARMACOLOGY. 11(6), 646-648.
(2011). From PDE3B to the regulation of energy homeostasis. CURRENT OPINION IN PHARMACOLOGY. 11(6), 676-682.
(2011). Phosphodiesterase 3A (PDE3A) Deletion Suppresses Proliferation of Cultured Murine Vascular Smooth Muscle Cells (VSMCs) via Inhibition of Mitogen-activated Protein Kinase (MAPK) Signaling and Alterations in Critical Cell Cycle Regulatory Proteins. JOURNAL OF BIOLOGICAL CHEMISTRY. 286(29), 26238-26249.
(2011). Phosphodiesterase 4D Regulates Baseline Sarcoplasmic Reticulum Ca2+ Release and Cardiac Contractility, Independently of L-Type Ca2+ Current. CIRCULATION RESEARCH. 109(9), 1024-U119.
(2011). Role of PDE3A in regulation of cell cycle progression in mouse vascular smooth muscle cells and oocytes: implications in cardiovascular diseases and infertility. CURRENT OPINION IN PHARMACOLOGY. 11(6), 725-729.
(2010). Compartmentalized Cyclic Adenosine 3 ',5 '-Monophosphate at the Plasma Membrane Clusters PDE3A and Cystic Fibrosis Transmembrane Conductance Regulator into Microdomains. MOLECULAR BIOLOGY OF THE CELL. 21(6), 1097-1110.
(2010). Expression and Regulation of Cyclic Nucleotide Phosphodiesterases in Human and Rat Pancreatic Islets. PLoS One. 5(12),
(2010). Female infertility in PDE3A(-/-) mice Polo-like kinase 1 (Plk1) may be a target of protein kinase A (PKA) and involved in meiotic arrest of oocytes from PDE3A(-/-) mice. CELL CYCLE. 9(23), 4720-4734.
(2009). Differential regulation of adipocyte PDE3B in distinct membrane compartments by insulin and the beta(3)-adrenergic receptor agonist CL316243: effects of caveolin-1 knockdown on formation/maintenance of macromolecular signalling complexes. BIOCHEMICAL JOURNAL. 424, 399-410.
(2009). Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 106(15), 6158-6163.
(2009). Phosphodiesterase 3B Is Localized in Caveolae and Smooth ER in Mouse Hepatocytes and Is Important in the Regulation of Glucose and Lipid Metabolism. PLoS One. 4(3),
(2009). Regulation of AMP-activated protein kinase by cAMP in adipocytes: Roles for phosphodiesterases, protein kinase B, protein kinase A, Epac and lipolysis. CELLULAR SIGNALLING. 21(5), 760-766.
(2009). STEROID-SPARING EFFECTS OF PENTOXIFYLLINE IN PULMONARY SARCOIDOSIS. SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES. 26(2), 121-131.
(2008). Expression, Activity, and Function of Phosphodiesterases in the Mature and Immature Ductus Arteriosus. PEDIATRIC RESEARCH. 64(5), 477-481.
(2007). Foxp3-dependent programme of regulatory T-cell differentiation. NATURE. 445(7129), 771-775.
(2007). Insulin-induced formation of macromolecular complexes involved in activation of cyclic nucleotide phosphodiesterase 3B (PDE3B) and its interaction with PKB. BIOCHEMICAL JOURNAL. 404, 257-268.
(2007). Long-term regulation of cyclic nucleotide phosphodiesterase type 3B and 4 in 3T3-L1 adipocytes. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 353(4), 1080-1085.
(2007). Multisite phosphorylation of adipocyte and hepatocyte phosphodiesterase 3B. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. 1773(4), 584-592.
(2007). Novel mechanisms of the regulation of Protein kinase B in adipocytes; implications for Protein kinase A, Epac, Phosphodiesterases 3 and 4. CELLULAR SIGNALLING. 19(1), 81-86.
(2007). Re-discovering PDE3 inhibitors - New opportunities for a long neglected target. CURRENT TOPICS IN MEDICINAL CHEMISTRY. 7(4), 421-436.
(2007). Role of phosphodiesterase type 3A and 3B in regulating platelet and cardiac function using subtype-selective knockout mice. CELLULAR SIGNALLING. 19(8), 1765-1771.
(2007). beta-cell PDE3B regulates Ca2+-stimulated exocytosis of insulin. CELLULAR SIGNALLING. 19(7), 1505-1513.
(2006). Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice. JOURNAL OF CLINICAL INVESTIGATION. 116(12), 3240-3251.
(2006). Early and rapid development of insulin resistance, islet dysfunction and glucose intolerance after high-fat feeding in mice overexpressing phosphodiesterase 3B. JOURNAL OF ENDOCRINOLOGY. 189(3), 629-641.
(2006). Effect of adipocyte beta(3)-adrenergic receptor activation on the type 2 diabetic MKR mice. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM. 290(6), E1227-E1236.
(2006). Expression of cyclic nucleotide phosphodiesterase 3A in isolated rat submandibular acini. ARCHIVES OF ORAL BIOLOGY. 51(2), 83-88.
(2006). Importance of cAMP-response element-binding protein in regulation of expression of the murine cyclic nucleotide phosphodiesterase 3B (Pde3b) gene in differentiating 3T3-L1 preadipocytes. JOURNAL OF BIOLOGICAL CHEMISTRY. 281(30), 21096-21113.
(2006). Plasma membrane cyclic nucleotide phosphodiesterase 3B (PDE3B) is associated with caveolae in primary adipocytes. CELLULAR SIGNALLING. 18(10), 1713-1721.
(2006). Role of PDE3B in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis in primary rat adipocytes. CELLULAR SIGNALLING. 18(3), 382-390.
(2005). Effects of the human immunodeficiency virus-protease inhibitor, ritonavir, on basal and catecholamine-stimulated lipolysis. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM. 90(6), 3251-3261.
(2005). Isoforms of cyclic nucleotide phosphodiesterase PDE3 and their contribution to cAMP hydrolytic activity in subcellular fractions of human myocardium. JOURNAL OF BIOLOGICAL CHEMISTRY. 280(47), 39168-39174.
(2004). Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female infertility. JOURNAL OF CLINICAL INVESTIGATION. 114(2), 196-205.
(2004). Editorial commentary. INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH. 16, S1-S3.
(2004). Milrinone efficiently potentiates insulin secretion induced by orally but not intravenously administered glucose in C57BL6J mice. EUROPEAN JOURNAL OF PHARMACOLOGY. 498(1-3), 319-323.
(2004). beta-cell-targeted overexpression of phosphodiesterase 3B in mice causes impaired insulin secretion, glucose intolerance, and deranged islet morphology. JOURNAL OF BIOLOGICAL CHEMISTRY. 279(15), 15214-15222.
(2003). Cyclic adenosine 3 ',5 '-monophosphate regulation of corticotropin-releasing hormone promoter activity in AtT-20 cells and in a transformed hypothalamic cell line. ENDOCRINOLOGY. 144(4), 1292-1300.
(2003). Cyclic nucleotide phosphodiesterase 5 and sildenafil: Promises realized. MOLECULAR PHARMACOLOGY. 63(6), 1209-1211.
(2003). Dual effects of pituitary adenylate cyclase-activating polypeptide and isoproterenol on lipid metabolism and signaling in primary rat adipocytes. ENDOCRINOLOGY. 144(12), 5293-5299.
(2003). Effect of the phosphodiesterase 4 inhibitor, rolipram, on retinoic acid-increased alkaline phosphatase activity in the mouse fibroblastic C3H1OT1/2 cell line. ARCHIVES OF ORAL BIOLOGY.
(2003). Phosphodiesterase 4 in osteoblastic osteosarcoma cells as a potential target for growth inhibition. ANTI-CANCER DRUGS. 14(5), 377-381.
(2003). Systematic search for single nucleotide polymorphisms in the 5 ' flanking region of the human phosphodiesterase 3B gene: absence of evidence for major effects of identified polymorphisms on susceptibility to Japanese type 2 diabetes. MOLECULAR GENETICS AND METABOLISM. 79(1), 43-51.
(2002). C-2-ceramide influences the expression and insulin-mediated regulation of cyclic nucleotide phosphodiesterase 3B and lipolysis in 3T3-L1 adipocytes. DIABETES. 51(3), 631-637.
(2002). Characterization of phosphodiesterase 3 in human malignant melanoma cell line. ANTICANCER RESEARCH. 22(6A), 3171-3174.
(2002). Expression and role of phosphodiesterase 3 in human squamous cell carcinoma KB cells. ANTI-CANCER DRUGS. 13(8), 875-880.
(2002). Important role of phosphodiesterase 3B for the stimulatory action of cAMP on pancreatic beta-cell exocytosis and release of insulin. JOURNAL OF BIOLOGICAL CHEMISTRY. 277(40), 37446-37455.
(2002). Isoforms of cyclic nucleotide phosphodiesterase PDE3A in cardiac myocytes. JOURNAL OF BIOLOGICAL CHEMISTRY. 277(41), 38072-38078.
(2002). Protein phosphatase 2A is the main phosphatase involved in the regulation of protein kinase B in rat adipocytes. CELLULAR SIGNALLING. 14(3), 231-238.
(2002). Ser-474 is the major target of insulin-mediated phosphorylation of protein kinase B beta in primary rat adipocytes. CELLULAR SIGNALLING. 14(2), 175-182.
(2002). Short-term regulation of PDE4 activity. BRITISH JOURNAL OF PHARMACOLOGY. 136(3), 339-340.
(2002). Tumor necrosis factor-alpha stimulates lipolysis in differentiated human Adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. DIABETES. 51(10), 2929-2935.
(2001). Expression of phosphodiesterase 3 in rat submandibular gland cell lines. ARCHIVES OF ORAL BIOLOGY. 46(5), 453-457.
(2001). Identification of a novel isoform of the cyclic-nucleotide phosphodiesterase PDE3A expressed in vascular smooth-muscle myocytes. BIOCHEMICAL JOURNAL. 353, 41-50.
(2001). Phosphodiesterase 3 as a potential target for therapy of malignant tumors in the submandibular gland. ANTI-CANCER DRUGS. 12(1), 79-83.
(2001). Regulation and function of the cyclic nucleotide phosphodiesterase (PDE3) gene family. 66, 241-277.
(2000). Cardiac type cGMP-inhibited phosphodiesterase (PDE3A) gene structure: Similarity and difference to adipocyte type PDE3B gene. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 268(3), 827-834.
(2000). Cyclic nucleotide phosphodiesterase 3B is a downstream target of protein kinase B and may be involved in regulation of effects of protein kinase B on thymidine incorporation in FDCP2 cells. JOURNAL OF IMMUNOLOGY. 164(9), 4678-4688.
(2000). Down-regulation of cyclic-nucleotide phosphodiesterase 3B in 3T3-L1 adipocytes induced by tumour necrosis factor alpha and cAMP. BIOCHEMICAL JOURNAL. 346, 337-343.
(2000). Functions of the N-terminal region of cyclic nucleotide phosphodiesterase 3 (PDE 3) isoforms. JOURNAL OF BIOLOGICAL CHEMISTRY. 275(16), 12331-12338.
(2000). Membrane localization of cyclic nucleotide phosphodiesterase 3 (PDES) - Two N-terminal, domains are required for the efficient targeting to, and association of, PDE3 with endoplasmic reticulum. JOURNAL OF BIOLOGICAL CHEMISTRY. 275(49), 38749-38761.
(2000). Phosphorylation of PDE3B by phosphatidylinositol 3-kinase associated with the insulin receptor. JOURNAL OF BIOLOGICAL CHEMISTRY. 275(14), 10093-10098.
(1999). Cyclic nucleotide phosphodiesterases (PDE) 3 and 4 in normal, malignant, and HTLV-1 transformed human lymphocytes. BIOCHEMICAL PHARMACOLOGY. 58(6), 935-950.
(1999). Cyclic nucleotide phosphodiesterases: Diverse regulators of cyclic nucleotide signals and inviting molecular targets for novel therapeutic agents. THROMBOSIS AND HAEMOSTASIS. 82(2), 407-411.
(1999). Evidence for the presence of several phosphodiesterase isoforms in brown adipose tissue of Zucker rats: modulation of PDE2 by the fa gene expression. 456(1), 207-210.
(1999). IL-3 and IL-4 activate cyclic nucleotide phosphodiesterases 3 (PDE3) and 4 (PDE4) by different mechanisms in FDCP2 myeloid cells. JOURNAL OF IMMUNOLOGY. 162(8), 4864-4875.
(1999). Increased mortality in type 2 diabetes patients using sulphonylurea and metformin in combination. DIABETOLOGIA. 42, A3-A3.
(1999). Mechanisms of inhibition of lipolysis by insulin, vanadate and peroxovanadate in rat adipocytes. BIOCHEMICAL JOURNAL. 339, 281-289.
(1999). Phosphorylation and activation of phosphodiesterase type 3B (PDE3B) in adipocytes in response to serine/threonine phosphatase inhibitors: deactivation of PDE3B in vitro by protein phosphatase type 2A. BIOCHEMICAL JOURNAL. 341, 839-845.
(1998). Insulin-induced phosphorylation and activation of phosphodiesterase 3B in rat adipocytes: Possible role for protein kinase B but not mitogen-activated protein kinase or p70 S6 kinase. ENDOCRINOLOGY. 139(1), 219-227.
(1998). Insulin-induced translocation of protein kinase B to the plasma membrane in rat adipocytes. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 246(1), 249-254.
(1998). Phosphorylation and activation of hormone-sensitive adipocyte phosphodiesterase type 3B. METHODS. 14(1), 43-53.
(1998). Protein kinase B is expressed in pancreatic beta cells and activated upon stimulation with insulin-like growth factor I. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 250(1), 181-186.
(1997). Differential expression of cyclic nucleotide phosphodiesterase 3 and 4 activities in human T cell clones specific for myelin basic protein. JOURNAL OF IMMUNOLOGY. 159(3), 1520-1529.
(1997). Protein kinase A-dependent activation of PDE4 (cAMP-specific cyclic nucleotide phosphodiesterase) in cultured bovine vascular smooth muscle cells. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. 1356(1), 64-70.
(1997). Regulation of hormone-sensitive lipase activity in adipose tissue. Methods in Enzymology. 286, 45-67.

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Academic Articles215