Genetics and cell biology
Genomics of renal diseases and hypertension
Our Clinical Research Unit works within the Nephrology and Dialysis Clinical Department of IRCCS Ospedale San Raffaele and mainly deals with kidney diseases, such as hypertension, acute and chronic renal failure, polycystic kidney disease, lupus nephritis, kidney stone disease.
Research activity
Focus of our projects is essential hypertension, a complex and multifactorial disease studied by different approaches: clinical (24-hour pressure monitoring, sodium sensitivity test, hyposodic diet, pharmacological trials), genomic (characterization of DNA polymorphisms in candidate genes), pharmacogenomic (therapy assignment based on patient's genetic characteristics), humoral biomarkers (endogenous ouabain, hormones, electrolytes) and environmental (lifestyle, sodium control in the diet).
Our goal is to implement a "precision medicine" aimed to identify genetic and haematochemical markers predicting the individual response to a particular treatment (pharmacological, dietary, etc.), protecting from organ complications and/or preventing adverse outcomes (stroke, infarction, acute renal failure).
Salvi E, Wang Z, Rizzi F, Gong Y, McDonough CW, Padmanabhan S, Hiltunen TP, Lanzani C, Zaninello R, Chittani M, Bailey KR, Sarin AP, Barcella M, Melander O, Chapman AB, Manunta P, Kotula KK, Glorioso N, Cusi D, Dominiczak AF, John JA, Barlassina C, Boerwinkle E, Cooper-Dehoff RM, Turner ST. Genome-Wide and gene-based meta-analyses identify novel loci influencing blood pressure response to hydrochlorothiazide. Hypertension 2017 Jan;69(1):51-59.
Villa L, Buono R, Ferrandi M, Molinari I, Benigni F, Bettiga A, Colciago G, Ikehata M, Messagio E, Rastaldi MP, Montorsi F, Salonia A, Manunta P. Ouabain contributes to kidney damage in a rat model of renal ischemia-reperfusion injury. Int J Mol Sci. 2016 Oct 14;17(10). pii: E1728.
Lanzani C, Gatti G, Citterio L, Messaggio E, Delli Carpini S, Simonini M, Casamassima N, Z agato L, Brioni E, Hamlyn JM, Manunta P. Lanosterol synthase gene polymorphisms and changes in Endogenous Ouabain in the response to low sodium intake. Hypertension 2016 Feb;67(2):342-8.
Pers TH et al. Biological interpretation of genome-wide association studies using predicted gene functions. Nat Commun. 2015 Jan 19;6:5890.
BignamiI E, Casamassima N, Frati E, Lanzani C, Corno L, Altieri O, Gottlieb S, Simonini M, Shah KB, Mizzi A, Messaggio E, Zangrillo A, Ferrandi M, Ferrari P, Bianchi G, Hamlyn JM, Manunta P. Preoperative endogenous ouabain predicts acute kidney injury in cardiac surgery patients. Crit Care Med. 2013 Mar;41(3):744-55.
Trudu M, Janas S, Lanzani C, Debaix H, Schaeffer C, Ikehata M, Citterio L, Demaretz S, Trevisani F, Ristagno G, Glaudemans B, Laghmanik, Dell’Antonio G, the Swiss Kidney Project on Genes in Hypertension (SKIPOGH) team 11, Loffing J, Rastaldi MG, Manunta P, Devuyst O, Rampoldi L. Common noncoding UMOD promoter variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression. Nat Med. 2013 Dec;19(12):1655-60.
Citterio L, Ferrandi M, Delli Carpini S, Simonini M, Kuznetsova T, Molinari I, Dell'Antonio G, Lanzani C, Merlino L, Brioni E, Staessen JA, Bianchi G, Manunta P. cGMP-Dependent protein kinase 1 polymorphisms underlie renal sodium handling impairment. Hypertension 2013 Dec;62(6):1027-33.
Salvi E et al. Genome-wide association study using a high-density SNP array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of eNOS. Hypertension 2012; 59(2): 248-255.
Lanzani C, Citterio L, Glorioso N, Manunta P, Tripodi G, Salvi E, Delli Carpini S, Ferrandi M, Messaggio E, Staessen JA, Cusi D, Macciardi F, Argiolas G, Valentini G, Ferrari P, Bianchi G also on behalf of OASIS-HT Investigators. 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.
Cusi D, Barlassina C, Azzani T, Casari G, CIitterio L, Devoto M, Glorioso N, Lanzani C, Manunta P, Righetti M, Riverea R, Stella P, Troffa C, Zagato L, Bianchi G. Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension. Lancet 1997; 349:1353-1357.
