Manunta Paolo Professore OrdinarioMedicineMED/14
Biography
Biography
Paolo MANUNTA, MD
Professor of Nephrology
Università Vita Salute San Raffaele
Chair and School of Nephrology
Director of Strategic Program in Nephrology and Dialysis
San Raffaele Scientific Institute
Education:
1985 University of Sassari, MD Medicine (cum laude)
1985-1989 University of Sassari, Speciality in Cardiology ,
1990-1993 University of MarylandSchool of Medicine, BaltimoreUSA. Post Doctoral Fellow, Department of Physiology (cum laude)
2000 University of Milan Speciality in Nephrology (cum laude)
Work History:
1983-1985 Student, Internal Medicine, University of Sassari
1985-1989 Resident in Cardiology at University of Sassari
1986-1990 “Emergency On call Service” on SassariHospital
1990-1993 “Post Doctoral Research Fellow” Department of Physiology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
1994 Cardiologist for the “Cardiology Service” of ASL °1 Sassari
1995-2000 Resident in Nephrology at University of Milan
1995-2007 Full time senior Clinical Assistent at the Division of Nephrology, Dialysis and Hypertension San Raffaele Hospital, Milan: Coordinator of Hypertension out patients clinic HSR, On-call service for the dialysis service of HSR, clinical duty of in-patients OU Nephrology
2002 Associate Professor of Nephrology
2007-present Chair of Nephrology, Director School of Nephrology UniSR
Research interests:
I started my research at the University of Sassari studying the role of ion transport (Na-K ATPase, Na/Li cotransport) in human primary hypertension with Prof. Nicola Glorioso. In the early 90s, a humoral Na pump inhibitor – long thought to be a key factor in hypertension, was isolated and identified as an Endogenous Ouabain (EO) by the Hamlyn laboratory at the University of Maryland working with the Upjohn Company. I joined the Hamlyn lab in Baltimore in 1990 as a postdoctoral fellow working in what is now called the field of “Ouabainomics” to study EO. My work in Baltimore was instrumental in proving that ouabain induced hypertension, that there were naturally occurring antagonists of its pressor effect and that dietary salt intake had significant effect on the circulating levels of EO in humans. After Baltimore, I returned to the University of Sassari for one year and from there joined (1994) the Bianchi group at San Raffaele Hospital. The Bianchi group identified (1997) adducin (ADD1) gene variants that cause high blood pressure in 25-30% of all hypertensives. By studying the transition from normotension to hypertension, in both experimental models and humans, different mechanistic phases were identified. In addition, much of my work continues to focus on the relationship of circulating EO with cardiovascular and renal diseases. We are widely regarded as the world leader in studies that link EO with disease and are continuing to investigate the role of EO in various clinical modalities associated with premature morbidity and mortality. We are especially interested in the key early phase events in the etiology of essential hypertension. For example, in at least one third to one half of patients with mild to moderate essential hypertension, the circulating levels of endogenous “ouabain” are elevated. A long series of findings suggest that ADD1 gene variants and EO stimulate the reno-tubular Na-K ATPase leading to increased renal Na reabsorption in the early phase of hypertension. In the later stages of hypertension, we found genetic variants that predict the progression towards end stage disease (ESRD). We continue to address the role of EO and genetics in patients including those with common chronic kidney diseases (CKD), left ventricular hypertrophy (LVH) and cardiovascular complications. Some of this work has involved large population studies, in collaboration with J. Staessen’s group in Belgium and demonstrates important roles for ADD1 gene variants and EO in CKD, ESRD and LVH.
Our translational medicine approach is now using pharmacogenomics to identify the genetic profiles that predict the blood pressure response to anti-hypertensive drugs. For example, a specific inhibitor of Adducin-EO mechanisms reduces blood pressure only in those patients that carry a specific genetic profile. This is the first example, to our knowledge, of personalized medicine being successfully applied in a complex disease. We expect that further studies of the genetic network involved will lead to a better understanding of the roles of key genes and hormones such as EO in the target organ complications in acute kidney injury (AKI), CKD and cardiac complications.
Publications and Academic Honors & Awards
1992 American Heart Association (Council of Hypertension).
1996 Italian-American Nephrology Society
2000 SIN Italian Nephrology Society (Top poster presentation)
2004 SIN Italian Nephrology Society (5 Tops oral presentation).
2004 European Hypertension Specialist of the European Hypertension Society
2005 SIN Italian Nephrology Society (Top poster presentation)
2008 ERA/EDTA Congress (Top oral presentation)
2008 13th International SHR Meeting (invited speaker)
2008 University of Maryland (Baltimora, USA), invited speaker at the Seminar “Link between salt and hypertension: role of Na+/CA++ exchanger gene and endogenous ouabain in hypertensive patients”
Member of the:
Italian Society of Hypertension
Italian Society of Nephrology
Italian Society of Experimental Biology
Scientific Committee of ASL Città di Milano (2001-2003 and 2008-2010): Hypertension: guidelines
European Hypertension Society
International Society of Hypertension
Clinical Hypertension Specialist of European Society of Hypertension (nomination 2004)
Member of the Editorial Board of:
Giornale Italiano di Nefrologia 2001-2008
Journal of Hypertension 2007-2010
World Journal of Hypertension
Full list of scientific publications of Prof. Paolo Manunta is available on web site
http://www.ncbi.nlm.nih.gov/pubmed
Selected peer reviewed publications
- Citterio L, Simonini M, Zagato L, Salvi E, Delli Carpini S, Lanzani C, Messaggio E, Casamassima N, Frau F, D’Avila F, Cusi D, Barlassina C, Manunta P. Genes involved in vasoconstriction and vasodilation system affect salt-sensitive hypertension. PLoS One 2011 May 9;6(5):e19620.
- Speliotes EK, Yerges-Armstrong LM, Wu J, Hernaez R, Kim LJ, Palmer CD, Gudnason V, Eiriksdottir G, Garcia ME, Launer LJ, Nalls MA, Clark JM, Mitchell BD, Shuldiner AR, Butler JL, Tomas M, Hoffmann U, Hwang SJ, Massaro JM, O’Donnell CJ, Sahani DV, Salomaa V, Schadt EE, Schwartz SM, Siscovick DS; NASH CRN; GIANT Consortium Manunta P; MAGIC Investigators, Voight BF, Carr JJ, Feitosa MF, Harris TB, Fox CS, Smith AV, Kao WH, Hirschhorn JN, Borecki IB; GOLD Consortium. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet 2011 Mar;7(3):e1001324.
- Jin Y, Kuznetsova T, Thijs L, Richart T, Stolarz-Skrzypek K, Liu Y, Fagard R, Manunta P, Bianchi G, Staessen JA. Association of echocardiographic left ventricular structure with the ACE D/I polymorphism: A meta-analysis. J Renin Angiotensin Aldosterone Syst 2011 Jan 27.
- Hamlyn JM, Manunta P. Endogenous ouabain: a link between sodium intake and hypertension. Curr Hypertens Rep 2011 Feb;13(1):14-20.
- Manunta P, Messaggio E, Casamassima N, Gatti G, Carpini SD, Zagato L, Hamlyn JM Endogenous ouabain in renal Na(+) handling and related diseases. Biochim Biophys Acta 2010; Dec;1802(12):1214-1218.
- Ferrandi M, Cusi D, Molinari I, Del Vecchio L, Barlassina C, Rastaldi MP, Schena FP, Macciardi F, Marcantoni C, Roccatello D, Peters LL, Armelloni S, Min L, Giardino L, Mattinzoli D, Camisasca C, Palazzo F, Manunta P, Ferrari P, Bianchi G. alpha- and beta-Adducin polymorphisms affect podocyte proteins and proteinuria in rodents and decline of renal function in human IgA nephropathy. J Mol Med 2010 Feb;88(2):203-217.
- Lanzani C, Citterio L, Glorioso N, Manunta P, Tripodi G, Salvi E, Carpini SD, Ferrandi M, Messaggio E, Staessen JA, Cusi D, Macciardi F, Argiolas G, Valentini G, Ferrari P, Bianchi G. Adducin- and ouabain-related gene variants predict the antihypertensive activity of rostafuroxin, part 2: clinical studies. Sci Transl Med 2010 Nov 24;2(59):59ra87.
- Dall’Asta C, Vedani P, Manunta P, Pizzocri P, Marchi M, Paganelli M, Folli F, Pontiroli AE. Effect of weight loss through laparoscopic gastric banding on blood pressure, plasma renin activity and aldosterone levels in morbid obesity. Nutr Metab Cardiovasc Dis 2009 Feb;19(2):110-114.
- Tripodi G, Citterio L, Kuznetsova T, Lanzani C, Florio M, Modica R, Messaggio E, Hamlyn JM, Zagato L, Bianchi G, Staessen JA, Manunta P. Steroid biosynthesis and renal excretion in human essential hypertension: association with blood pressure and endogenous ouabain. Am J Hypertens 2009;22:357-363.
- Kuznetsova T, Manunta P, Yu J, Thjis L, Richart T, Fagard RJ, Messaggio E, Casamassima N, Bianchi G, Staessen JA. Left ventricular geometry and endogenous ouabain in a Flemish population. J Hypertens 2009; 27(9):1884-1891.
- Stella P, Manunta P, Mallamaci F, Melandri M, Spotti D, Tripepi G, Hamlyn JM, Malatino LS, Bianchi G, Zoccali C. Endogenous ouabain and cardiomyopathy in dialysis patients. J Int Medicine 2008;263:274-280.
- Manunta P, Lavery G, Lanzani C, Braund PS, Simonini M, Bodycode C, Zagato L, Delli Carpini S, Tantardini C, Brioni E, Bianchi G, Samani NJ. Physiological interaction between ADD1 and WNK1-NEDD4L pathways on sodium related blood pressure regulation. Hypertension 2008;52:366-372.
- Li Y, Zagato L, Kuznetsova T, Tripodi G, Zerbini G, Richart T, Thjis L, Manunta P, Wang JG, Bianchi G, Staessen J. The ACE I/D and ADD1 Gly460Trp polymorphisms: from ACE activity to cardiovascular outcome. Hypertension 2007;49:1291-1297.
- Manunta P, Citterio L, Lanzani C, Ferrandi M. Adducin polymorphisms and the treatment of hypertension. Pharmacogenomics 2007;8(5):465-472.
- Pitzalis MV, Hamlyn JM, Messaggio E, Iacoviello M, Forleo C, Romito R, De Tommasi E, Bianchi G, Rizzon P, Manunta P. Independent and Incremental Prognostic Value of Endogenous Ouabain in Idiopathic Dilated Cardiomyopathy. Eur J Heart Failure 2006 Mar;8(2):179-186.
- Manunta P, Hamilton BP, Hamlyn JM. Salt intake and depletion increase circulating levels of endogenous ouabain in normal men. Am J Physiol Regul Integr Comp Physiol 2006;290:R553-559.
- Manunta P, Ferrandi M. Cardiac glycosides and cardiomyopathy. Hypertension 2006; 47(3):343-344.
- Lanzani C, Citterio L, Jankaricova M, Sciarrone MT, Barlassina C, Fattori S, Messaggio E, Serio CD, Zagato L, Cusi D, Hamlyn JM, Stella A, Bianchi G, Manunta P. Role of the adducin family genes in human essential hypertension. J Hypertens 2005 Mar;23(3):543-549.
- Manunta P, Bianchi G. Low-salt diet and diuretic effect on blood pressure and organ damage. J Am Soc Nephrol 2004 Jan;15 Suppl 1:S43-6
- Wang JG, Staessen JA, Messaggio E, Nawrot T, Fagard R, Hamlyn JM, Bianchi G, Manunta P. Salt, endogenous ouabain and blood pressure interactions in the general population. J Hypertens 2003 Aug;21(8):1475-81.
- Sciarrone MT, Stella P, Barlassina C, Manunta P, Lanzani C, Bianchi G, Cusi D. ACE and alpha-adducin polymorphism as markers of individual response to diuretic therapy. Hypertension 2003 Mar;41(3):398-403.
- Barlassina C, Lanzani C, Manunta P, Bianchi G. Genetics of essential hypertension: from families to genes. J Am Soc Nephrol 2002 Nov;13 Suppl 3:S155-S164.
- Manunta P, Messaggio E, Ballabeni C, Sciarrone MT, Lanzani C, Ferrandi M, Hamlyn JM, Cusi D, Galletti F, Bianchi G. Salt Sensitivity Study Group of the Italian Society of Hypertension. Plasma ouabain-like factor during acute and chronic changes in sodium balance in essential hypertension. Hypertension 2001 Aug;38(2):198-203.
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