Staff Collaborate Conference Room

Ulrich Broeckel, MD

BioFPOMCWlogo

Ulrich Broeckel, MD

Chief, Genomic Pediatrics; Center Associate Director; Professor

Locations

  • Genomic Pediatrics

Biography

The Broeckel lab (@broeckel_lab) specializes in the identification and functional evaluation of genes and their variants involved in cardiovascular and other complex diseases. Our research interests include: left ventricular hypertrophy, myocardial infarction, coronary artery disease, end-stage renal disease, and hypertension with projects based on large epidemiological studies in clinical cohorts. In addition, we perform microarray-based diagnostic tests with an emphasis in pharmacogenomics for both Children’s Hospital of Wisconsin (CHW) and St. Jude Children’s Research Hospital and run the Nucleic Acid Extraction Core for investigators at Children’s Research Institute.

We use genome-wide association (GWA) studies to identify genes involved in complex diseases. Based on the evidence of association provided by GWA, we establish molecular and cell-based assays to investigate gene function. One way that we currently evaluate gene function utilizes the latest in next generation (NextGen) sequencing technologies. We have or are in the process of establishing strategies to examine expression levels of microRNA, single nucleotide polymorphim (SNP) and copy number (CNV) variations, and perform pharmacogenetic custom captures on multiple platforms such as the Ion Torrent Personal Genome Machine (PGM™), the Ion Torrent Proton™ and the Illumina HiSeq™.

We are also a part of a groundbreaking multicenter NHLBI initiative to generate patient-derived human-induced pluripotent stem cell (hiPSC) for the study of complex disease with our collaborators at Cellular Dynamics, International. This collaboration will result in the high-throughput development of hiPSC-derived cardiomyocytes generated from patients participating in a major hypertension epidemiological study. The cardiomyoctes will be characterized using a variety of in vitro methods and NextGen sequencing and will also be used to investigate and understand the complex molecular mechanisms and pathways underlying the genetic basis of an increase in Left Ventricular Mass leading to Left Ventricular Hypertrophy as a common and major risk factor for cardiovascular disease.

In conjunction with CHW, we launched the Advanced Genomics (AGEN) laboratory in 2009, which is regulated by the College of American Pathologists (CAP), licensed through CHW. Utilizing the Affymetrix Genome-Wide Human SNP Array 6.0 containing 1.8 million markers including SNP and CNV variations, we are able to look at duplications and deletions in patients with abnormalities to provide an innovative method in the diagnosis of genetic disorders for clinical care.

Our lab is also CLIA certified as the Developmental and Neurogenetics Laboratory (DNL). We work closely with St. Jude Children’s Research Hospital to test patient samples, looking for genetic variation of metabolic capacity. Patient DNA is tested on the Affymetrix Drug Metabolism Enzymes and Transporters (DMET™) Plus platform that uses state-of-the-art star allele translations tables and additional CNV analysis for CYP2D6 to lead to the most comprehensive interpretation for each patient’s treatment regimen.

Our pursuit of large scale epidemiological studies in clinical cohorts allows us to evaluate the effect and impact of SNPs identified in GWA studies with regard to their clinical relevance. Currently, the Broeckel lab contributes one MCW component to the Wisconsin Genomics Initiative, a consortium including our group and MCW as well as the Marshfield Clinic and the University of Wisconsin, Madison and Milwaukee.

Ongoing studies

  • Family Based Genetic Analysis for Genes Related to Inflammation and Myocardial Infarction (NHLBI)
  • Genetic Basis of Coronary Artery Disease and Coronary Collateralization (NHLBI)
  • Pediatric DNA Biobank
  • Functional GWAS for LVH using iPS-derived Cardiomyocytes: The HyperGEN ciPS Study (NHLBI)
  • HyperGen: Genetic Epidemiology of Left Ventricular Hypertrophy Genetics of CRP in Myocardial Function (NHLBI)
  • Genetics of Myocardial Infarction and Related Risk factors (NHLBI)
  • Molecular Genetics of Hypertension
  • Genetic Predisposition to End-Stage Renal Disease Epidemiology
  • The Wisconsin Genomics Initiative

Publications

  • Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits.

    (Kraja AT, Liu C, Fetterman JL, Graff M, Have CT, Gu C, Yanek LR, Feitosa MF, Arking DE, Chasman DI, Young K, Ligthart S, Hill WD, Weiss S, Luan J, Giulianini F, Li-Gao R, Hartwig FP, Lin SJ, Wang L, Richardson TG, Yao J, Fernandez EP, Ghanbari M, Wojczynski MK, Lee WJ, Argos M, Armasu SM, Barve RA, Ryan KA, An P, Baranski TJ, Bielinski SJ, Bowden DW, Broeckel U, Christensen K, Chu AY, Corley J, Cox SR, Uitterlinden AG, Rivadeneira F, Cropp CD, Daw EW, van Heemst D, de Las Fuentes L, Gao H, Tzoulaki I, Ahluwalia TS, de Mutsert R, Emery LS, Erzurumluoglu AM, Perry JA, Fu M, Forouhi NG, Gu Z, Hai Y, Harris SE, Hemani G, Hunt SC, Irvin MR, Jonsson AE, Justice AE, Kerrison ND, Larson NB, Lin KH, Love-Gregory LD, Mathias RA, Lee JH, Nauck M, Noordam R, Ong KK, Pankow J, Patki A, Pattie A, Petersmann A, Qi Q, Ribel-Madsen R, Rohde R, Sandow K, Schnurr TM, Sofer T, Starr JM, Taylor AM, Teumer A, Timpson NJ, de Haan HG, Wang Y, Weeke PE, Williams C, Wu H, Yang W, Zeng D, Witte DR, Weir BS, Wareham NJ, Vestergaard H, Turner ST, Torp-Pedersen C, Stergiakouli E, Sheu WH, Rosendaal FR, Ikram MA, Franco OH, Ridker PM, Perls TT, Pedersen O, Nohr EA, Newman AB, Linneberg A, Langenberg C, Kilpeläinen TO, Kardia SLR, Jørgensen ME, Jørgensen T, Sørensen TIA, Homuth G, Hansen T, Goodarzi MO, Deary IJ, Christensen C, Chen YI, Chakravarti A, Brandslund I, Bonnelykke K, Taylor KD, Wilson JG, Rodriguez S, Davies G, Horta BL, Thyagarajan B, Rao DC, Grarup N, Davila-Roman VG, Hudson G, Guo X, Arnett DK, Hayward C, Vaidya D, Mook-Kanamori DO, Tiwari HK, Levy D, Loos RJF, Dehghan A, Elliott P, Malik AN, Scott RA, Becker DM, de Andrade M, Province MA, Meigs JB, Rotter JI, North KE.) Am J Hum Genet. 2019 Jan 03;104(1):112-138.

  • Concordance between glucose-6-phosphate dehydrogenase (G6PD) genotype and phenotype and rasburicase use in patients with hematologic malignancies.

    (Robinson KM, Yang W, Haidar CE, Hankins JS, Jay DW, Kornegay N, Rubnitz JE, Broeckel U, Cheng C, Pui CH, Jeha S, Relling MV.) Pharmacogenomics J. 2018 Sep 12.

  • Clinical correlates and heritability of cardiac mechanics: The HyperGEN study.

    (Khan SS, Kim KA, Peng J, Aguilar FG, Selvaraj S, Martinez EE, Baldridge AS, Sha J, Irvin MR, Broeckel U, Arnett DK, Rasmussen-Torvik LJ, Shah SJ.) Int J Cardiol. 2019 Jan 01;274:208-213.

  • Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

    (Feitosa MF, Kraja AT, Chasman DI, Sung YJ, Winkler TW, Ntalla I, Guo X, Franceschini N, Cheng CY, Sim X, Vojinovic D, Marten J, Musani SK, Li C, Bentley AR, Brown MR, Schwander K, Richard MA, Noordam R, Aschard H, Bartz TM, Bielak LF, Dorajoo R, Fisher V, Hartwig FP, Horimoto ARVR, Lohman KK, Manning AK, Rankinen T, Smith AV, Tajuddin SM, Wojczynski MK, Alver M, Boissel M, Cai Q, Campbell A, Chai JF, Chen X, Divers J, Gao C, Goel A, Hagemeijer Y, Harris SE, He M, Hsu FC, Jackson AU, Kähönen M, Kasturiratne A, Komulainen P, Kühnel B, Laguzzi F, Luan J, Matoba N, Nolte IM, Padmanabhan S, Riaz M, Rueedi R, Robino A, Said MA, Scott RA, Sofer T, Stančáková A, Takeuchi F, Tayo BO, van der Most PJ, Varga TV, Vitart V, Wang Y, Ware EB, Warren HR, Weiss S, Wen W, Yanek LR, Zhang W, Zhao JH, Afaq S, Amin N, Amini M, Arking DE, Aung T, Boerwinkle E, Borecki I, Broeckel U, Brown M, Brumat M, Burke GL, Canouil M, Chakravarti A, Charumathi S, Ida Chen YD, Connell JM, Correa A, de Las Fuentes L, de Mutsert R, de Silva HJ, Deng X, Ding J, Duan Q, Eaton CB, Ehret G, Eppinga RN, Evangelou E, Faul JD, Felix SB, Forouhi NG, Forrester T, Franco OH, Friedlander Y, Gandin I, Gao H, Ghanbari M, Gigante B, Gu CC, Gu D, Hagenaars SP, Hallmans G, Harris TB, He J, Heikkinen S, Heng CK, Hirata M, Howard BV, Ikram MA, InterAct Consortium, John U, Katsuya T, Khor CC, Kilpeläinen TO, Koh WP, Krieger JE, Kritchevsky SB, Kubo M, Kuusisto J, Lakka TA, Langefeld CD, Langenberg C, Launer LJ, Lehne B, Lewis CE, Li Y, Lin S, Liu J, Liu J, Loh M, Louie T, Mägi R, McKenzie CA, Meitinger T, Metspalu A, Milaneschi Y, Milani L, Mohlke KL, Momozawa Y, Nalls MA, Nelson CP, Sotoodehnia N, Norris JM, O'Connell JR, Palmer ND, Perls T, Pedersen NL, Peters A, Peyser PA, Poulter N, Raffel LJ, Raitakari OT, Roll K, Rose LM, Rosendaal FR, Rotter JI, Schmidt CO, Schreiner PJ, Schupf N, Scott WR, Sever PS, Shi Y, Sidney S, Sims M, Sitlani CM, Smith JA, Snieder H, Starr JM, Strauch K, Stringham HM, Tan NYQ, Tang H, Taylor KD, Teo YY, Tham YC, Turner ST, Uitterlinden AG, Vollenweider P, Waldenberger M, Wang L, Wang YX, Wei WB, Williams C, Yao J, Yu C, Yuan JM, Zhao W, Zonderman AB, Becker DM, Boehnke M, Bowden DW, Chambers JC, Deary IJ, Esko T, Farrall M, Franks PW, Freedman BI, Froguel P, Gasparini P, Gieger C, Jonas JB, Kamatani Y, Kato N, Kooner JS, Kutalik Z, Laakso M, Laurie CC, Leander K, Lehtimäki T, Study LC, Magnusson PKE, Oldehinkel AJ, Penninx BWJH, Polasek O, Porteous DJ, Rauramaa R, Samani NJ, Scott J, Shu XO, van der Harst P, Wagenknecht LE, Wareham NJ, Watkins H, Weir DR, Wickremasinghe AR, Wu T, Zheng W, Bouchard C, Christensen K, Evans MK, Gudnason V, Horta BL, Kardia SLR, Liu Y, Pereira AC, Psaty BM, Ridker PM, van Dam RM, Gauderman WJ, Zhu X, Mook-Kanamori DO, Fornage M, Rotimi CN, Cupples LA, Kelly TN, Fox ER, Hayward C, van Duijn CM, Tai ES, Wong TY, Kooperberg C, Palmas W, Rice K, Morrison AC, Elliott P, Caulfield MJ, Munroe PB, Rao DC, Province MA, Levy D.) PLoS One. 2018;13(6):e0198166.

  • Age- and Genotype-Dependent Variability in the Protein Abundance and Activity of Six Major Uridine Diphosphate-Glucuronosyltransferases in Human Liver.

    (Bhatt DK, Mehrotra A, Gaedigk A, Chapa R, Basit A, Zhang H, Choudhari P, Boberg M, Pearce RE, Gaedigk R, Broeckel U, Leeder JS, Prasad B.) Clin Pharmacol Ther. 2019 Jan;105(1):131-141.

  • Hepatic Abundance and Activity of Androgen- and Drug-Metabolizing Enzyme UGT2B17 Are Associated with Genotype, Age, and Sex.

    (Bhatt DK, Basit A, Zhang H, Gaedigk A, Lee SB, Claw KG, Mehrotra A, Chaudhry AS, Pearce RE, Gaedigk R, Broeckel U, Thornton TA, Nickerson DA, Schuetz EG, Amory JK, Leeder JS, Prasad B.) Drug Metab Dispos. 2018 06;46(6):888-896.

  • Human IL12RB1 expression is allele-biased and produces a novel IL12 response regulator.

    (Reeme AE, Claeys TA, Aggarwal P, Turner AJ, Routes JM, Broeckel U, Robinson RT.) Genes Immun. 2018 Mar 30.

  • A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.

    (Sung YJ, Winkler TW, de Las Fuentes L, Bentley AR, Brown MR, Kraja AT, Schwander K, Ntalla I, Guo X, Franceschini N, Lu Y, Cheng CY, Sim X, Vojinovic D, Marten J, Musani SK, Li C, Feitosa MF, Kilpeläinen TO, Richard MA, Noordam R, Aslibekyan S, Aschard H, Bartz TM, Dorajoo R, Liu Y, Manning AK, Rankinen T, Smith AV, Tajuddin SM, Tayo BO, Warren HR, Zhao W, Zhou Y, Matoba N, Sofer T, Alver M, Amini M, Boissel M, Chai JF, Chen X, Divers J, Gandin I, Gao C, Giulianini F, Goel A, Harris SE, Hartwig FP, Horimoto ARVR, Hsu FC, Jackson AU, Kähönen M, Kasturiratne A, Kühnel B, Leander K, Lee WJ, Lin KH, 'an Luan J, McKenzie CA, Meian H, Nelson CP, Rauramaa R, Schupf N, Scott RA, Sheu WHH, Stančáková A, Takeuchi F, van der Most PJ, Varga TV, Wang H, Wang Y, Ware EB, Weiss S, Wen W, Yanek LR, Zhang W, Zhao JH, Afaq S, Alfred T, Amin N, Arking D, Aung T, Barr RG, Bielak LF, Boerwinkle E, Bottinger EP, Braund PS, Brody JA, Broeckel U, Cabrera CP, Cade B, Caizheng Y, Campbell A, Canouil M, Chakravarti A, CHARGE Neurology Working Group, Chauhan G, Christensen K, Cocca M, COGENT-Kidney Consortium, Collins FS, Connell JM, de Mutsert R, de Silva HJ, Debette S, Dörr M, Duan Q, Eaton CB, Ehret G, Evangelou E, Faul JD, Fisher VA, Forouhi NG, Franco OH, Friedlander Y, Gao H, GIANT Consortium, Gigante B, Graff M, Gu CC, Gu D, Gupta P, Hagenaars SP, Harris TB, He J, Heikkinen S, Heng CK, Hirata M, Hofman A, Howard BV, Hunt S, Irvin MR, Jia Y, Joehanes R, Justice AE, Katsuya T, Kaufman J, Kerrison ND, Khor CC, Koh WP, Koistinen HA, Komulainen P, Kooperberg C, Krieger JE, Kubo M, Kuusisto J, Langefeld CD, Langenberg C, Launer LJ, Lehne B, Lewis CE, Li Y, Lifelines Cohort Study, Lim SH, Lin S, Liu CT, Liu J, Liu J, Liu K, Liu Y, Loh M, Lohman KK, Long J, Louie T, Mägi R, Mahajan A, Meitinger T, Metspalu A, Milani L, Momozawa Y, Morris AP, Mosley TH Jr, Munson P, Murray AD, Nalls MA, Nasri U, Norris JM, North K, Ogunniyi A, Padmanabhan S, Palmas WR, Palmer ND, Pankow JS, Pedersen NL, Peters A, Peyser PA, Polasek O, Raitakari OT, Renström F, Rice TK, Ridker PM, Robino A, Robinson JG, Rose LM, Rudan I, Sabanayagam C, Salako BL, Sandow K, Schmidt CO, Schreiner PJ, Scott WR, Seshadri S, Sever P, Sitlani CM, Smith JA, Snieder H, Starr JM, Strauch K, Tang H, Taylor KD, Teo YY, Tham YC, Uitterlinden AG, Waldenberger M, Wang L, Wang YX, Wei WB, Williams C, Wilson G, Wojczynski MK, Yao J, Yuan JM, Zonderman AB, Becker DM, Boehnke M, Bowden DW, Chambers JC, Chen YI, de Faire U, Deary IJ, Esko T, Farrall M, Forrester T, Franks PW, Freedman BI, Froguel P, Gasparini P, Gieger C, Horta BL, Hung YJ, Jonas JB, Kato N, Kooner JS, Laakso M, Lehtimäki T, Liang KW, Magnusson PKE, Newman AB, Oldehinkel AJ, Pereira AC, Redline S, Rettig R, Samani NJ, Scott J, Shu XO, van der Harst P, Wagenknecht LE, Wareham NJ, Watkins H, Weir DR, Wickremasinghe AR, Wu T, Zheng W, Kamatani Y, Laurie CC, Bouchard C, Cooper RS, Evans MK, Gudnason V, Kardia SLR, Kritchevsky SB, Levy D, O'Connell JR, Psaty BM, van Dam RM, Sims M, Arnett DK, Mook-Kanamori DO, Kelly TN, Fox ER, Hayward C, Fornage M, Rotimi CN, Province MA, van Duijn CM, Tai ES, Wong TY, Loos RJF, Reiner AP, Rotter JI, Zhu X, Bierut LJ, Gauderman WJ, Caulfield MJ, Elliott P, Rice K, Munroe PB, Morrison AC, Cupples LA, Rao DC, Chasman DI.) Am J Hum Genet. 2018 03 01;102(3):375-400.

  • PLCγ-dependent mTOR signalling controls IL-7-mediated early B cell development.

    (Yu M, Chen Y, Zeng H, Zheng Y, Fu G, Zhu W, Broeckel U, Aggarwal P, Turner A, Neale G, Guy C, Zhu N, Chi H, Wen R, Wang D.) Nat Commun. 2017 11 13;8(1):1457.

  • Genetic and Nongenetic Factors Associated with Protein Abundance of Flavin-Containing Monooxygenase 3 in Human Liver.

    (Xu M, Bhatt DK, Yeung CK, Claw KG, Chaudhry AS, Gaedigk A, Pearce RE, Broeckel U, Gaedigk R, Nickerson DA, Schuetz E, Rettie AE, Leeder JS, Thummel KE, Prasad B.) J Pharmacol Exp Ther. 2017 Nov;363(2):265-274.

  • Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function.

    (Wild PS, Felix JF, Schillert A, Teumer A, Chen MH, Leening MJG, Völker U, Großmann V, Brody JA, Irvin MR, Shah SJ, Pramana S, Lieb W, Schmidt R, Stanton AV, Malzahn D, Smith AV, Sundström J, Minelli C, Ruggiero D, Lyytikäinen LP, Tiller D, Smith JG, Monnereau C, Di Tullio MR, Musani SK, Morrison AC, Pers TH, Morley M, Kleber ME, Aragam J, Benjamin EJ, Bis JC, Bisping E, Broeckel U, Cheng S, Deckers JW, Del Greco M F, Edelmann F, Fornage M, Franke L, Friedrich N, Harris TB, Hofer E, Hofman A, Huang J, Hughes AD, Kähönen M, Investigators K, Kruppa J, Lackner KJ, Lannfelt L, Laskowski R, Launer LJ, Leosdottir M, Lin H, Lindgren CM, Loley C, MacRae CA, Mascalzoni D, Mayet J, Medenwald D, Morris AP, Müller C, Müller-Nurasyid M, Nappo S, Nilsson PM, Nuding S, Nutile T, Peters A, Pfeufer A, Pietzner D, Pramstaller PP, Raitakari OT, Rice KM, Rivadeneira F, Rotter JI, Ruohonen ST, Sacco RL, Samdarshi TE, Schmidt H, Sharp ASP, Shields DC, Sorice R, Sotoodehnia N, Stricker BH, Surendran P, Thom S, Töglhofer AM, Uitterlinden AG, Wachter R, Völzke H, Ziegler A, Münzel T, März W, Cappola TP, Hirschhorn JN, Mitchell GF, Smith NL, Fox ER, Dueker ND, Jaddoe VWV, Melander O, Russ M, Lehtimäki T, Ciullo M, Hicks AA, Lind L, Gudnason V, Pieske B, Barron AJ, Zweiker R, Schunkert H, Ingelsson E, Liu K, Arnett DK, Psaty BM, Blankenberg S, Larson MG, Felix SB, Franco OH, Zeller T, Vasan RS, Dörr M.) J Clin Invest. 2017 May 01;127(5):1798-1812.

  • The promoter polymorphism -860 A > G (rs3814159) is associated with increased gene transcription, protein expression, CD39/NTPDase1 enzymatic activity, and thromboembolism risk.

    (Maloney JP, Branchford BR, Brodsky GL, Cosmic MS, Calabrese DW, Aquilante CL, Maloney KW, Gonzalez JR, Zhang W, Moreau KL, Wiggins KL, Smith NL, Broeckel U, Di Paola J.) FASEB J. 2017 07;31(7):2771-2784.