Massimo Attanasio, M.D.

Identification of genes that are responsible for human diseases is a powerful tool for the progress of medical research. Using genetic techniques it is possible to identify mutations that alter the function of a protein and result in human pathologies. Such discoveries bring invaluable insights in the molecular defects and the mechanisms underlying the diseases and might open the way to future diagnostic methods and therapies.

The research in my laboratory aims to identify genes that when mutated result in the development of kidney diseases by studying families in which the disease is genetically transmitted, with a particular focus on autosomal recessive forms of polycystic kidney disease and familiar forms of renal stones disease, hypercalciuria and nephrocalcinosis.

Using gene mapping techniques I recently identified a gene that when mutated causes nephronophthisis, a rare autosomal recessive pathology that affects children and young adults, is characterized by the development of cysts in the kidneys and results in progressive deterioration of the renal function and renal insufficiency.

In my laboratory we also apply molecular and cellular biology techniques to define the function of the protein products of the mutated genes and their role in the pathologic process, with the final intent of clarifying the mechanisms that from the genetic mutation lead to the development of the disease.

Medical School

University of Naples (1990), Medicine

• Genetics of inherited kidney diseases
• Human genetics
• Molecular biology
• Molecular genetics

Featured Publications

Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis.

Attanasio M, Uhlenhaut NH, Sousa VH, O’toole JF, Otto E, Anlag K, Klugmann C, Treier AC, Helou J, Sayer JA, Seelow D, Nurnberg G, Becker C, Chudley AE, Nurnberg P, Hildebrandt F, Treier M. Nat Genet. 2007 39 1018-1024

Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible.

Hinkes B, Wiggins RC, Gbadegesin R, Vlangos CN, Seelow D, Nurnberg G, Garg P, Verma R, Chaib H, Hoskins BE, Ashraf S, Becker C, Hennies HC, Goyal M, Wharram BL, Schachter AD, Mudumana S, Drummond I, Kerjaschki D, Waldherr R, Dietrich A, Ozaltin F, Bakkaloglu A, Cleper R, Basel-Vanagaite L, Pohl M, Griebel M, Tsygin AN, Soylu A, Muller D, Sorli CS, Bunney TD, Katan M, Liu J, Attanasio M, O’toole JF et al. Nat Genet. 2006 38 1397-405

The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4.

15. Sayer JA, Otto EA, O’toole JF, Nurnberg G, Kennedy MA, Becker C, Hennies HC, Helou J, Attanasio M, Fausett BV, Utsch B, Khanna H, Liu Y, Drummond I, Kawakami I, Kusakabe T, Tsuda M, Ma L, Lee H, Larson RG, Allen SJ, Wilkinson CJ, Nigg EA, Shou C, Lillo C, Williams DS, Hoppe B, Kemper MJ, Neuhaus T, Parisi MA, Glass IA, Petry M, Kispert A, Gloy J, Ganner A, Walz G, Zhu X, Goldman D, Nurnberg P, Swaroop A, Leroux MR, Hildebrandt F. Nat Genet. 2006 38:674-81

The genetic components of idiopathic nephrolithiasis.

Attanasio M. Pediatr Nephrol. June 2010 [Epub ahead of print].

Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression.

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. Hum Mol Genet. 2010 15;19:1985-97

Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy.

O’Toole JF, Liu Y, Davis EE, Westlake CJ, Attanasio M, Otto EA, Seelow D, Nurnberg G, Becker C, Nuutinen M, Karppa M, Ignatius J, Uusimaa J, Pakanen S, Jaakkola E, van den Heuvel LP, Fehrenbach H, Wiggins R, et. al J Clin Invest. 2010 120:791-802

Nephrocystin-3 is required for ciliary function in zebrafish embryos.

Zhou W, Dai J, Attanasio M, Hildebrandt F. Am J Physiol Renal Physiol. 2010 299:F55-62

Hypomorphic Mutations in Meckelin (MKS3/TMEM67) cause Nephronophthisis with Liver Fibrosis (NPHP11).

Otto EA, Tory K, Attanasio M, Zhou W, Chaki M, Paruchuri Y, Wise EL, Utsch B, Wolf MT, Becker C, Nurnberg G, Nurnberg P, Nayir A, Saunier S, Antignac C, Hildebrandt F. J Med Genet. June 2009 46 663-670

• American Society of Nephrology Carl W. Gottschalk Research Scholar Award
  (2010)