Daniela Salvemini, Ph.D.
 | Associate Professor (2009-present). Department of Pharmacological and Physiological Science, School of Medicine, Saint Louis University, Saint Louis University School of Medicine, St Louis, MO, USA. Research Professor of Internal Medicine (2005-2009). Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Saint Louis University, St Louis, MO, USA. Research Professor of Pharmacological and Physiological Sciences (2006-2009). Department of Pharmacological and Physiological Sciences, Saint Louis University School of Medicine, St Louis, MO, USA. University of London, 1990 salvemd@slu.edu |
Research Summary
Our research focus is in the pharmacological mechanisms of pain. We employ translational medicine to bridge the gap between basic research and clinical sciences.
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Chronic severe pain is a significant global health problem. In the
Reactive oxygen and nitrogen species (nitroxide species) in particular superoxide (O2-), nitric oxide (NO) or peroxynitrite (ONOO-) the product of their interaction are potent pro-inflammatory mediators implicated in a variety of disease processes.
Using a multidisciplinary approach including molecular, bioanalytical, biochemical and pharmacological tools my lab is actively engaged in the following projects:
1) We are interested in the biosynthetic pathways leading to nitroxidative species (in particular but not restricted to nitric oxide, superoxide and peroxynirite) during the development of pain of several etiologies in particular chronic inflammatory pain (arthritis), chronic neuropathic pain (nerve injuries), chemotherapy induced neuropathic pain (induced by commonly used chemotherapeutics such as Taxol or Cisplatin). We are also particularly interested in understanding the role of nitroxidative stress in the development of opiate induced pain and tolerance.
2) Our efforts address the relative contribution of nitroxidative species and their overall significance in nociceptive processing in these settings. To this end we are interested in understanding how reactive nitroxidative species modify mitochondrial function; how they contribute to neuroimmune activation; how they modify through post-translational modifications, the function of key proteins known to play essential roles in nociception and; how they impact neuronal apoptosis.
3) Another key research interest of my lab is to understand the role of the ceramide metabolic pathway in the development of peripheral and central sensitization and to investigate the reciprocal interaction between this pathway and the nitroxidative pathway.
Through our key collaborative efforts with chemistry groups at other academic institutions, we are involved in synthesizing novel chemical tools /probes to study nitroxidative stress and signaling molecules at the molecular, cellular and organism level that help us unravel the therapeutic importance of these pathways in pain thus addressing major unmet medical needs with huge socioeconomic consequences.
Honors and Awards
NIH/NIAMSD (2009-2011) "Targeting the relief of chronic pain with orally active peroxynitrite decomposition catalysts" (PI): 1RC1AR058231-01
The Oxygen Club of Greater Washington, D.C and the Society for Experimental Biology and Medicine, D.C Award (2002)
Magna Graecia Prize (2000). For “The contribution of the scientific advancement of research in Southern Italy”, Italy.
Novartis Prize In Pharmacology (1997). For her contribution to Pharmacology.
Searle Discovery Research Achievement Award (1997). “Recognizing achievements and leadership in Superoxide Dismutase Project”
Searle Discovery Research Achievement Award (1996). “Recognizing achievements and leadership in Nitric Oxide Synthase and Superoxide Dismutase Projects”
William Julius Mickle Fellowship (1991). Awarded by The University of London. For: “An investigator under 35 years of age, who has in the opinion of the Committee, done most to advance medical art or science within the preceding five years”
Young Investigators Award (1991). Awarded by The International Society of Thrombosis and Haemostasis, For: “The excellence and originality of the work presented on the interactions between nitric oxide platelets and vascular smooth muscle cells”
Young Investigators Award (1989). Awarded by The British Society of Thrombosis and Haemostasis: For “The excellence and originality of the work on the regulation of platelet function by oxygen-derived free radicals”
Grant Support
R01, NIH/NIDA (2008-2013) (PI). Role of peroxynitrite in morphine hyperalgesia and tolerance. Amount funded: $1,771,000
R21, NIH/NIDA (2008-2010) (PI). Role of ceramide in morphine hyperalgesia and tolerance. Amount funded: $392,325
Saint Louis University Seed Funds (2007-2008) (PI). Ceramide-novel target in the development of opiate-induced hyperalgesia and tolerance. Amount funded: $22,000
Saint Louis University Seed Funds (2006-2008) (PI). Ceramide- novel target in the development of opiate-induced hyperalgesia and tolerance. Amount funded: $25,000
NIH/NHLBI, HL073896 (2004-2009) (Consultant). Pulmonary Collectins, Hyaluronan and Macrophages.
NIH/NCI, 1 R43 CA9320301 (8/06/01-7/31/02) (PI). M40403 and IL-2 Induced Hypotension. Amount funded: $ 261,230
NIH/NHLBI, 1 R43 HL68362-01 (9/30/01-3/29/02) (PI). SODm for Management of Ischemic Heart Disease. Amount funded: $ 104,100
NIH/NIDA, 1R43 DA13534-01 (7/01/00 -12/31/00) (PI). Superoxide Dismutase Mimetics for Management of Pain. Amount funded: $ 320,100
DHHS/FDA, R43 FD-01585-01 (9/30/00-3/31/01) (PI). Inactivation of Catecholamines in Septic Shock. Amount funded: $ 100,000
Professional Memberships
American Thoracic Society, International Association for the Study of Pain (I.A.S.P), American Society of Pharmacology and Experimental Therapeutics
Professional Experience:
Associate Professor (2009-present). Department of Pharmacological and Physiological Science, School of Medicine, Saint Louis University, Saint Louis University School of Medicine, St Louis, MO, USA.
Research Professor of Internal Medicine (2005-2009). Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Saint Louis University, St Louis, MO, USA.
Research Professor of Pharmacological and Physiological Sciences (2006-2009). Department of Pharmacological and Physiological Sciences, Saint Louis University School of Medicine, St Louis, MO, USA.
Adjunct Professor of Pharmacological and Physiological Sciences (1994-2006). Department of Pharmacological and Physiological Sciences, Saint Louis University School of Medicine, St Louis, MO, USA.
Visiting Professor (2007-present). Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy.
Adjunct Professor of Molecular Pharmacology (2000-present), Department of Pharmacology (Faculty of Pharmacy of Catanzaro, Italy).
Senior Vice President of Research (2003-2005). Metaphore Pharmaceuticals, Inc, St. Louis. MO, USA.
Vice President of Biological and Pharmacological Research (2001-2003). Metaphore Pharmaceuticals, Inc, St. Louis. MO, USA.
Director of Biology (1999-2001). Metaphore Pharmaceuticals, Inc, St. Louis. MO, USA.
Research Scientist II and Project Leader (1997-1999). G.D. Searle, Discovery Research, St. Louis. MO, USA
Research Scientist I (1995-1997). G.D. Searle, Discovery Research, St. Louis. MO, USA
Senior Research Investigator (1994-1995). G.D. Searle, Discovery Research, St. Louis. MO, USA
Post-doctoral Fellow (1992-1994). Department of Molecular Pharmacology, Monsanto Corporate Research, St. Louis, USA.
Post-doctoral Fellow (1990-1992). The William Harvey Research Institute, Saint Bartholomew’s Hospital Medical College, Charterhouse Square, London ECIM6BQ, UK.
Editorial Boards:
International Journal of Inflammation
Faculty Appointments
Associate Professor (2009-present). Department of Pharmacological and Physiological Science, School of Medicine, Saint Louis University, Saint Louis University School of Medicine, St Louis, MO, USA.
Research Professor of Internal Medicine (2005-2009). Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Saint Louis University, St Louis, MO, USA.
Research Professor of Pharmacological and Physiological Sciences (2006-2009). Department of Pharmacological and Physiological Sciences, Saint Louis University School of Medicine, St Louis, MO, USA.
Teaching Experience
Current Research Activities
Publications
Publications (from 2007-present):
Bryant, L, Doyle, T, Chen, Z, Cuzzocrea, S, Masini, E, Vinci, MC, Esposito, E, Mazzon, E, Petrusca, DN, Petrache, I, Salvemini, D. (2009). Spinal Ceramide and Neuronal Apoptosis in Morphine Antinociceptive Tolerance. Neuroscience Letters. In press.
T. Doyle, L. Bryant, I. Batinic-Haberle, J. Little, S. Cuzzocrea, E. Masini, I. Spasojevic, D. Salvemini, Supraspinal Inactivation of Mitochondrial Superoxide Dismutase is a Source of Peroxynitrite in the Development of Morphine Antinociceptive Tolerance,Neuroscience (2009). In Press.
M.M. Ndengele, S. Cuzzocrea, E. Masini, M.C. Vinci, E. Esposito, C. Muscoli, D.N. Petrusca, V. Mollace, E. Mazzon, D. Li, I. Petrache, G.M. Matuschak, D. Salvemini, Spinal ceramide modulates the development of morphine antinociceptive tolerance via peroxynitrite-mediated nitroxidative stress and neuroimmune activation, The Journal of pharmacology and experimental therapeutics 329 (2009) 64-75.
I. Batinic-Haberle, M.M. Ndengele, S. Cuzzocrea, J.S. Reboucas, I. Spasojevic, D. Salvemini, Lipophilicity is a critical parameter that dominates the efficacy of metalloporphyrins in blocking the development of morphine antinociceptive tolerance through peroxynitrite-mediated pathways, Free radical biology & medicine 46 (2009) 212-219.
I. Batinic-Haberle, S. Cuzzocrea, J.S. Reboucas, G. Ferrer-Sueta, E. Mazzon, R. DiPaola, R. Radi, I. Spasojevic, L. Benov, D. Salvemini, Pure MnTBAP selectively scavenges peroxynitrite over superoxide: comparison of pure and commercial MnTBAP samples to MnTE-2-PyP in two models of oxidative stress injury, an SOD-specific Escherichia coli model and carrageenan-induced pleurisy, Free radical biology & medicine 46 (2009) 192-201.
I. Kos, J.S. Reboucas, G. DeFreitas-Silva, D. Salvemini, Z. Vujaskovic, M.W. Dewhirst, I. Spasojevic, I. Batinic-Haberle, Lipophilicity of potent porphyrin-based antioxidants: comparison of ortho and meta isomers of Mn(III) N-alkylpyridylporphyrins, Free radical biology & medicine 47 (2009) 72-78.
E. Masini, E. Ragazzo, M.C. Vinci, S. Nistri, L. Cinci, R. Mastroianni, R.L. Thurmond, D. Salvemini, A selective H4R antagonist prevents antigen-induced asthma-like reaction and airway inflammation in guinea pigs, Inflamm Res 58 Suppl 1 (2009) 9-10.
S. Cuzzocrea, T. Genovese, E. Mazzon, E. Esposito, C. Crisafulli, R. Di Paola, P. Bramanti, D. Salvemini, Fumonisin B1 reduces the development of multiple organ failure induced by zymosan in mice, Shock 31 (2009) 170-177.
S. Cuzzocrea, H.P. Deigner, T. Genovese, E. Mazzon, E. Esposito, C. Crisafulli, R. Di Paola, P. Bramanti, G. Matuschak, D. Salvemini, Inhibition of ceramide biosynthesis ameliorates pathological consequences of spinal cord injury, Shock 31 (2009) 634-644.
M.M. Ndengele, S. Cuzzocrea, E. Esposito, E. Mazzon, R. Di Paola, G.M. Matuschak, D. Salvemini, Cyclooxygenases 1 and 2 contribute to peroxynitrite-mediated inflammatory pain hypersensitivity, Faseb J 22 (2008) 3154-3164.
E. Masini, L. Giannini, S. Nistri, L. Cinci, R. Mastroianni, W. Xu, S.A. Comhair, D. Li, S. Cuzzocrea, G.M. Matuschak, D. Salvemini, Ceramide: a key signaling molecule in a Guinea pig model of allergic asthmatic response and airway inflammation, The Journal of pharmacology and experimental therapeutics 324 (2008) 548-557.
S. Cuzzocrea, R. Di Paola, T. Genovese, E. Mazzon, E. Esposito, C. Crisafulli, P.Bramanti, D. Salvemini, Anti-inflammatory and anti-apoptotic effects of fumonisin B1, an inhibitor of ceramide synthase, in a rodent model of splanchnic ischemia and reperfusion injury, The Journal of pharmacology and experimental therapeutics 327 (2008) 45-57.
M. Kondapaneni, J.R. McGregor, D. Salvemini, V.E. Laubach, W.E. Samlowski, Inducible nitric oxide synthase (iNOS) is not required for IL-2-induced hypotension and vascular leak syndrome in mice, J Immunother 31 (2008) 325-333.
C. Muscoli, S. Cuzzocrea, M.M. Ndengele, V. Mollace, F. Porreca, F. Fabrizi, E. Esposito, E. Masini, G.M. Matuschak, D. Salvemini, Therapeutic manipulation of peroxynitrite attenuates the development of opiate-induced antinociceptive tolerance in mice, The Journal of clinical investigation 117 (2007) 3530-3539.
Reviews and Scholarly Writings
Salvemini, D & Timchenko, A. (2009). Role of nitro-oxidative stress in pain. In “The Review Book on Nitric Oxide and Disease Processes” Research Signpost Publications, USA. Richardson, V and Wallace, A editors. In press.
D. Salvemini, W. Neumann, Targeting peroxynitrite driven nitroxidative stress with synzymes: A novel therapeutic approach in chronic pain management, Life sciences (2009). In press
D. Salvemini, W.L. Neumann, Peroxynitrite: a strategic linchpin of opioid analgesic tolerance, Trends in pharmacological sciences 30 (2009) 194-202.
D. Salvemini, Peroxynitrite and opiate antinociceptive tolerance: a painful reality, Archives of biochemistry and biophysics 484 (2009) 238-244.
S. Cuzzocrea, D. Salvemini, Molecular mechanisms involved in the reciprocal regulation of clooxygenase and nitric oxide synthate enzymes, Kidney international 71 (2007) 290-297.
For a complete list of Dr. Salvemini's publications, click here: http://www.ncbi.nlm.nih.gov/pubmed/
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