The identification of genes responsible for human diseases has made significant contribution to 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 provide invaluable insights into the molecular defects and the mechanisms underlying diseases and may open the way to future diagnostic methods and therapies. Research in my laboratory aims to identify genes that when mutated result in the development of renal pathologies by studying families in which the disease is genetically transmitted. Our research is particularly focused 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 (NPHP7/GLIS2) that when mutated causes nephronophthisis, a rare autosomal recessive pathology that affects children and young adults. Nephronophthisis is characterized by the development of cysts in the kidneys and results in progressive deterioration of the renal function and renal insufficiency. Uncovering the role of GLIS2 in nephronophthisis has contributed new information about the mechanisms that result in the development of fibrosis in this affection. In my laboratory we also apply molecular and cellular biology techniques to define the function of the protein products of mutated genes and their role in the pathologic process, with the objective of clarifying the mechanisms that from the genetic mutation lead to the development of the disease.
RESEARCH INTERESTS
Genetics of inherited kidney diseases
Human genetics
Molecular genetics
Molecular biology
RECENT PUBLICATIONS
Otto EA, Helou J, Allen SJ, O’Toole JF, Wise EL, Ashraf S, Attanasio M, Zhou W, Wolf MT, Hildebrandt F., "Mutation analysis in nephronophthisis using a combined approach of homozygosity mapping, CEL I endonuclease cleavage, and direct sequencing." Hum Mutat., 29:418-26, 2008
Hoefele J, Wolf MT, O’Toole JF, Otto EA, Schultheiss U, Deschenes G, Attanasio M, Utsch B, Antignac C, Hildebrandt F., "Evidence of oligogenic inheritance in nephronophthisis." J Am Soc Nephrol., 18:2789-95, 2007
Chang B, Khanna H, Hawes N, Jimeno D, He S, Lillo C, Parapuram SK, Cheng H, Scott A, Hurd RE, Sayer JA, Otto EA, Attanasio M, O’toole JF, Jin G, Shou C, Hildebrandt F, Williams DS, Heckenlively JR, Swaroop A., "In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse." Hum Mol Genet., 15:1847-57, 2006
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., "The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4." Nat Genet., 38:674-81, 2006
SIGNIFICANT PUBLICATIONS
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., "Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis." Nat Genet., 39:1018-1024, 2007
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., "Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible." Nat Genet., 38:1397-405, 2006
Otto EA, Loeys B, Khanna H, Hellemans J, Sudbrak R, Fan S, Muerb U, O’Toole JF, Helou J, Attanasio M, Utsch B, Sayer JA, Lillo C, Jimeno D, Coucke P, De Paepe A, Reinhardt R, Klages S, Tsuda M, Kawakami I, Kusakabe T, Omran H, Imm A, Tippens M, Raymond PA, Hill J, Beales P, He S, Kispert A, Margolis B, Williams DS, Swaroop A, Hildebrandt F., "Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin." Nat Genet., 37:282-8, 2005
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