Friedhelm Hildebrandt, M.D.
Investigator, Howard Hughes Medical Institute
Professor of Pediatrics
Professor of Human Genetics
Frederick G. L. Huetwell Professor for the Cure and Prevention of Birth Defects
Doris Duke Distinguished Clinical Scientist
My lab's work is concerned with the identification and functional characterization of single-gene causes of kidney diseases in children. My group has identified 14 novel kidney disease genes. This work implicated the primary cilium and centrosomes in nephronophthisis and contributed to the identification of "ciliopathies" as a new class of human disease. Gene identification also extends to nephrotic syndrome and congenital malformations of the kidney and urinary tract. My lab studies the function of newly identified disease genes in disease models of mice and zebrafish. Recently, we have developed efficient methods for gene identification using total human exome capture and massively parallel (NextGen) sequencing.
Olbrich H, Fliegauf M, Hoefele J, Kispert A, Otto E, Volz A, T Wolf MT, Sasmaz G, Trauer U, Reinhardt R, Sudbrak R, Antignac C, Gretz N, Schermer B, Benzing T, Hildebrandt F, Omran H. Mutations of NPHP3 cause nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis. Nature Genet 34:455-9, 2003.
Otto EA, Schermer B, Obara T, O'Toole JF, Hiller KS, Mueller AM, Ruf R, Hoefele J, Beekmann F, Landau D, Foreman JW, Goodship JA, Strachan T, Kispert A, Wolf MT, Gagnadoux MF, Nivet H, Antignac C, Walz G, Drummond IA, Benzing T, Hildebrandt F. Inversin mutations cause NPHP2, linking renal cystic disease to the function of primary cilia and left-right axis determination. Nature Genet 34:413-20, 2003 (Edit p. 355).
Otto EA, Loeys B, Khanna H, Hellemans J, Sudbrak R, Fan S, et al. & Hildebrandt F. A novel ciliary IQ domain protein, NPHP5, is mutated in Senior-Loken syndrome (nephronophthisis with retinitis pigmentosa), and interacts with RPGR and calmodulin. Nature Genet 37:282-8, 2005.
Hildebrandt F, Otto EA. Cilia and Centrosomes: A unifying pathogenic concept for cystic kidney disease? Nature Rev Genet 6:928-40, 2005.
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. A novel centrosomal protein, nephrocystin-6, is mutated in Joubert syndrome and activates transcription factor ATF4. Nature Genet 38:674-681, 2006.
Hinkes BG, Wiggins RC, Gbadegesin R, Vlangos CN, Seelow D, Nurnberg G, Garg P, Verma R, Chaib H, HoskinsBE , Ashraf S, Becker C, Hennies HC, Goyal M, Wharram BL, Schachter AD, 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, Katan M, Liu J, Attanasio M, O'Toole JF, Hasselbacher K, Mucha B, Otto EA, Airik R, Kispert A, Kelley GG, Smrcka AV, Gudermann T, Holzman LB, Nurnberg P, Hildebrandt F. Positional cloning of PLCE1 mutations as the first cause of a nephrotic syndrome variant which may be reversible. Nature Genet 38:1397-1405, 2006 (editorial p. 1390)
1Attanasio M, 1Uhlenhaut HN, Sousa V, Dr. O'Toole JF, Otto E, Anlag K, Klugmann C, Treier AC, Sayer JA, Helou H, Seelow D, Nuernberg G, Becker C, Chudley A, Nuernberg P, 1Hildebrandt F, 1Treier M. Loss of GLIS2, a Kruppel-like zinc finger transcription factor, causes nephronophthisis in humans and mice by increased apoptosis and fibrosis. Nature Genet 39:1018-24, 2007 (1equal contribution)
O'Toole JF, Liu Y, Davis EE, Westlake CJ, Attanasio M, Otto EA, 45 authors and Hildebrandt F. Mutations in XPNPEP3, Encoding a mitochondrial protein, cause a nephronophthisis-like nephropathy. J Clin Invest 120:791-802, 2010
Hildebrandt F. Genetic kidney diseases. Lancet 375:1287, 2010
Otto EA, HurdTW, Airik R, Chaki M, Zhou W, and 49 authors and Hildebrandt F.Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nature Genet, in press 2010