Name: Luca Rampoldi

DTI position: Associate Telethon Scientist 

Research field: Molecular bases of renal disorders: Medullary Cystic Kidney Disease type 2, Familial Juvenile Hyperuricemic Nephropathy, Glomerulocystic Kidney Disease 

Hosting institute: San Raffaele Scientific Institute

Projects funded: click here

Contacts: Molecular Genetics of Renal Disorders Unit, Division of Genetics and Cell Biology, Via Olgettina, 58, 20132, Milan, Italy. Phone: +39 0226434947, Fax: +39 0226434767, rampoldi.luca@hsr.it 

Research field

I received my undergraduate degree in Biology from the University of Milan in 1994. In 1999 I received my Ph.D. degree in Genetic Sciences from the University of Padua where I worked under the supervision of Prof. Danieli on the genetics of neuromuscular disorders. During the same year I was awarded two travelling fellowships from the University of Padua and Fondazione Telethon to carry out a postdoctoral training in the laboratory of Prof. Anthony Monaco at the Wellcome Trust Centre for Human Genetics in Oxford. Here I worked on the molecular genetics of Chorea-acanthocytosis, a rare hereditary neurodegenerative disease, and identified the gene mutated in the disease. In 2002 I joined as a postdoctoral fellow the laboratory of Giorgio Casari at the San Raffaele Scientific Institute in Milan where I started to work on the molecular bases of hereditary kidney diseases caused by mutations in UMOD, the gene encoding uromodulin. I carried out the first functional characterisation of UMOD mutations demonstrating that they lead to intracellular retention and aggregation of mutant protein, a key step in the disease pathogenesis. In 2004 I entered the Dulbecco Telethon Institute as Assistant Telethon Scientist and in 2010 I was awarded the Associate Telethon Scientist position. During these years my lab has actively worked in the field of hereditary renal disorders, through the generation of cellular models and more recently of a mouse model of UMOD-associated kidney diseases. My work is aimed at the identification of the molecular mechanisms that lead to the disease and their targeting for therapeutic intervention.

Selected publications:

Rampoldi L, Dobson-Stone C, Rubio JP, Danek A, Chalmers RM, Wood NW, Verellen C, Ferrer X, Malandrini A, Fabrizi GM, Brown R, Vance J, Pericak-Vance M, Rudolf G, Carrè S, Alonso E, Manfredi M, Németh AH, Monaco AP, “A conserved sorting-associated protein is mutated in Chorea-acanthocytosis” Nat Genet 2001, 28:119-20. 
http://www.ncbi.nlm.nih.gov/pubmed/11381253 

Rampoldi L, Danek A, Monaco AP, “Clinical features and molecular bases of neuroacanthocytosis” J Mol Med 2002, 80(8):475-91. 
http://www.ncbi.nlm.nih.gov/pubmed/12185448 

Rampoldi L, Caridi G, Santon D, Boaretto F, Bernascone I, Lamorte G, Tardanico R, Dagnino M, Colussi G, Francesco Scolari, Ghiggeri GM, Amoroso A, Casari G, “Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics” Hum Mol Genet 2003, 12(24):3369-84. 
http://www.ncbi.nlm.nih.gov/pubmed/14570709 

Scolari F, Caridi G, Rampoldi L, Tardanico R, Izzi C, Pirulli D, Amoroso A, Casari G, Ghiggeri GM, “Uromodulin storage diseases: clinical aspects and mechanisms” Am J Kidney Dis 2004, 44(6):987-99. 
http://www.ncbi.nlm.nih.gov/pubmed/15558519 

Tinschert S, Ruf N, Bernascone I, Sacherer K, Lamorte G, Neumayer HH, Nurnberg P, Luft FC, Rampoldi L, “Functional consequences of a novel uromodulin mutation in a family with familial juvenile hyperuricaemic nephropathy” Nephrol Dial Transplant 2004, 19(12):3150-4.
http://www.ncbi.nlm.nih.gov/pubmed/15575003 

Bernascone I, Vavassori S, Di Pentima A, Santambrogio S, Lamorte G, Amoroso A, Scolari F, Ghiggeri GM, Casari G, Polishchuk R, Rampoldi L, “Defective intracellular trafficking of uromodulin mutant isoforms” Traffic 2006, 7(11):1567-79. 
http://www.ncbi.nlm.nih.gov/pubmed/17010121 

Santambrogio S, Cattaneo A, Bernascone I, Schwend T, Jovine L, Bachi A, Rampoldi L, “Urinary uromodulin carries an intact ZP domain generated by a conserved C-terminal proteolytic cleavage” Biochem Biophys Res Commun 2008, 370(3):410-3. 
http://www.ncbi.nlm.nih.gov/pubmed/18375198 

Schaeffer C, Santambrogio S, Perucca S, Casari G, Rampoldi L, “Analysis of uromodulin polymerization provides new insights into the mechanisms regulating ZP domain-mediated protein assembly” Mol Biol Cell 2009, 20(2):589-99. 
http://www.ncbi.nlm.nih.gov/pubmed/19005207 

Zaucke F, Boehnlein JM, Steffens S, Polishchuk RS, Rampoldi L, Fischer A, Pasch A, Boehm CW, Baasner A, Attanasio M, Hoppe B, Hopfer H, Beck BB, Sayer JA, Hildebrandt F, Wolf MT, “Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression” Hum Mol Genet 2010, 19(10):1985-97.
http://www.ncbi.nlm.nih.gov/pubmed/20172860 

Bernascone I, Janas S, Ikehata M, Trudu M, Corbelli A, Schaeffer C, Rastaldi MP, Devuyst O, Rampoldi L, “A transgenic mouse model for uromodulin-associated kidney diseases shows specific tubulo-interstitial damage, urinary concentrating defect and renal failure” Hum Mol Genet 2010, 19(15):2998-3010. 
http://www.ncbi.nlm.nih.gov/pubmed/20472742 

Group members: 

Céline Schaeffer (Postdoc), schaeffer.celine@hsr.it 
Martina Brunati (PhD student), brunati.martina@hsr.it 
Matteo Trudu (Research fellow), trudu.matteo@hsr.it 
Simone Perucca (Research fellow), perucca.simone@hsr.it