Staff Collaborate Conference Room

Ulrich Broeckel, MD

UlrichBroeckel_Academic Profile

Ulrich Broeckel, MD

Professor, Pediatrics; Adjunct Professor of Medicine, Physiology and School of Pharmacy; Chief, Section of Genomic Pediatrics; Associate Director, Pharmacogenomics, Genomic Sciences and Precision Medicine Center

Locations

  • Genomic Pediatrics

Contact Information

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 Wisconsin (Children's) 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 polymorphism (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 cardiomyocytes 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 Children's, we launched the Advanced Genomics (AGEN) laboratory in 2009, which is regulated by the College of American Pathologists (CAP), licensed through Children's. 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

Research Experience

  • Blood Pressure
  • Cardiovascular Diseases
  • Coronary Artery Disease
  • DNA Mutational Analysis
  • Gene Expression Profiling
  • Genetic Association Studies
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genetic Variation
  • Genome, Human
  • Genome-Wide Association Study

Methodologies and Techniques

  • Case-Control Studies
  • DNA
  • DNA Copy Number Variations
  • Drug-Related Side Effects and Adverse Reactions
  • Exome
  • Gene Expression Profiling
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genetic Variation
  • Genetics, Population
  • Genome-Wide Association Study

Leadership Positions

  • Associate Director for Pharmacogenomics, Genomic Sciences and Precision Medicine Ctr
  • Chief, Section Genomic Pediatrics
  • Research Unit Leader: Genetics and Genomics, Children's Research Institute

Publications

  • Characterization of Reference Materials with an Association for Molecular Pathology Pharmacogenetics Working Group Tier 2 Status: CYP2C9, CYP2C19, VKORC1, CYP2C Cluster Variant, and GGCX: A GeT-RM Collaborative Project.

    (Pratt VM, Turner A, Broeckel U, Dawson DB, Gaedigk A, Lynnes TC, Medeiros EB, Moyer AM, Requesens D, Vetrini F, Kalman LV.) J Mol Diagn. 2021 08;23(8):952-958 PMID: 34020041 SCOPUS ID: 2-s2.0-85109633971 05/22/2021

  • Variant-specific inflation factors for assessing population stratification at the phenotypic variance level.

    (Sofer T, Zheng X, Laurie CA, Gogarten SM, Brody JA, Conomos MP, Bis JC, Thornton TA, Szpiro A, O'Connell JR, Lange EM, Gao Y, Cupples LA, Psaty BM, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Rice KM.) Nat Commun. 2021 06 09;12(1):3506 PMID: 34108454 PMCID: PMC8190158 SCOPUS ID: 2-s2.0-85107746519 06/11/2021

  • Identification of CYP2D6 Haplotypes that Interfere with Commonly Used Assays for Copy Number Variation Characterization.

    (Turner AJ, Aggarwal P, Boone EC, Haidar CE, Relling MV, Derezinski AD, Broeckel U, Gaedigk A.) J Mol Diagn. 2021 05;23(5):577-588 PMID: 33631352 PMCID: PMC8176139 SCOPUS ID: 2-s2.0-85104414851 02/26/2021

  • Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices.

    (Natarajan P, Pampana A, Graham SE, Ruotsalainen SE, Perry JA, de Vries PS, Broome JG, Pirruccello JP, Honigberg MC, Aragam K, Wolford B, Brody JA, Antonacci-Fulton L, Arden M, Aslibekyan S, Assimes TL, Ballantyne CM, Bielak LF, Bis JC, Cade BE, Do R, Doddapaneni H, Emery LS, Hung YJ, Irvin MR, Khan AT, Lange L, Lee J, Lemaitre RN, Martin LW, Metcalf G, Montasser ME, Moon JY, Muzny D, O'Connell JR, Palmer ND, Peralta JM, Peyser PA, Stilp AM, Tsai M, Wang FF, Weeks DE, Yanek LR, Wilson JG, Abecasis G, Arnett DK, Becker LC, Blangero J, Boerwinkle E, Bowden DW, Chang YC, Chen YI, Choi WJ, Correa A, Curran JE, Daly MJ, Dutcher SK, Ellinor PT, Fornage M, Freedman BI, Gabriel S, Germer S, Gibbs RA, He J, Hveem K, Jarvik GP, Kaplan RC, Kardia SLR, Kenny E, Kim RW, Kooperberg C, Laurie CC, Lee S, Lloyd-Jones DM, Loos RJF, Lubitz SA, Mathias RA, Martinez KAV, McGarvey ST, Mitchell BD, Nickerson DA, North KE, Palotie A, Park CJ, Psaty BM, Rao DC, Redline S, Reiner AP, Seo D, Seo JS, Smith AV, Tracy RP, Vasan RS, Kathiresan S, Cupples LA, Rotter JI, Morrison AC, Rich SS, Ripatti S, Willer C, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, FinnGen, Peloso GM.) Nat Commun. 2021 04 12;12(1):2182 PMID: 33846329 PMCID: PMC8042019 SCOPUS ID: 2-s2.0-85104367584 04/14/2021

  • Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

    (Graff M, Justice AE, Young KL, Marouli E, Zhang X, Fine RS, Lim E, Buchanan V, Rand K, Feitosa MF, Wojczynski MK, Yanek LR, Shao Y, Rohde R, Adeyemo AA, Aldrich MC, Allison MA, Ambrosone CB, Ambs S, Amos C, Arnett DK, Atwood L, Bandera EV, Bartz T, Becker DM, Berndt SI, Bernstein L, Bielak LF, Blot WJ, Bottinger EP, Bowden DW, Bradfield JP, Brody JA, Broeckel U, Burke G, Cade BE, Cai Q, Caporaso N, Carlson C, Carpten J, Casey G, Chanock SJ, Chen G, Chen M, Chen YI, Chen WM, Chesi A, Chiang CWK, Chu L, Coetzee GA, Conti DV, Cooper RS, Cushman M, Demerath E, Deming SL, Dimitrov L, Ding J, Diver WR, Duan Q, Evans MK, Falusi AG, Faul JD, Fornage M, Fox C, Freedman BI, Garcia M, Gillanders EM, Goodman P, Gottesman O, Grant SFA, Guo X, Hakonarson H, Haritunians T, Harris TB, Harris CC, Henderson BE, Hennis A, Hernandez DG, Hirschhorn JN, McNeill LH, Howard TD, Howard B, Hsing AW, Hsu YH, Hu JJ, Huff CD, Huo D, Ingles SA, Irvin MR, John EM, Johnson KC, Jordan JM, Kabagambe EK, Kang SJ, Kardia SL, Keating BJ, Kittles RA, Klein EA, Kolb S, Kolonel LN, Kooperberg C, Kuller L, Kutlar A, Lange L, Langefeld CD, Le Marchand L, Leonard H, Lettre G, Levin AM, Li Y, Li J, Liu Y, Liu Y, Liu S, Lohman K, Lotay V, Lu Y, Maixner W, Manson JE, McKnight B, Meng Y, Monda KL, Monroe K, Moore JH, Mosley TH, Mudgal P, Murphy AB, Nadukuru R, Nalls MA, Nathanson KL, Nayak U, N'Diaye A, Nemesure B, Neslund-Dudas C, Neuhouser ML, Nyante S, Ochs-Balcom H, Ogundiran TO, Ogunniyi A, Ojengbede O, Okut H, Olopade OI, Olshan A, Padhukasahasram B, Palmer J, Palmer CD, Palmer ND, Papanicolaou G, Patel SR, Pettaway CA, Peyser PA, Press MF, Rao DC, Rasmussen-Torvik LJ, Redline S, Reiner AP, Rhie SK, Rodriguez-Gil JL, Rotimi CN, Rotter JI, Ruiz-Narvaez EA, Rybicki BA, Salako B, Sale MM, Sanderson M, Schadt E, Schreiner PJ, Schurmann C, Schwartz AG, Shriner DA, Signorello LB, Singleton AB, Siscovick DS, Smith JA, Smith S, Speliotes E, Spitz M, Stanford JL, Stevens VL, Stram A, Strom SS, Sucheston L, Sun YV, Tajuddin SM, Taylor H, Taylor K, Tayo BO, Thun MJ, Tucker MA, Vaidya D, Van Den Berg DJ, Vedantam S, Vitolins M, Wang Z, Ware EB, Wassertheil-Smoller S, Weir DR, Wiencke JK, Williams SM, Williams LK, Wilson JG, Witte JS, Wrensch M, Wu X, Yao J, Zakai N, Zanetti K, Zemel BS, Zhao W, Zhao JH, Zheng W, Zhi D, Zhou J, Zhu X, Ziegler RG, Zmuda J, Zonderman AB, Psaty BM, Borecki IB, Cupples LA, Liu CT, Haiman CA, Loos R, Ng MCY, North KE.) Am J Hum Genet. 2021 04 01;108(4):564-582 PMID: 33713608 PMCID: PMC8059339 SCOPUS ID: 2-s2.0-85103409847 03/14/2021

  • Donor-specific phenotypic variation in hiPSC cardiomyocyte-derived exosomes impacts endothelial cell function.

    (Turner A, Aggarwal P, Matter A, Olson B, Gu CC, Hunt SC, Lewis CE, Arnett DK, Lorier R, Broeckel U.) Am J Physiol Heart Circ Physiol. 2021 03 01;320(3):H954-H968 PMID: 33416449 PMCID: PMC8294700 SCOPUS ID: 2-s2.0-85102212257 01/09/2021

  • Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program.

    (Taliun D, Harris DN, Kessler MD, Carlson J, Szpiech ZA, Torres R, Taliun SAG, Corvelo A, Gogarten SM, Kang HM, Pitsillides AN, LeFaive J, Lee SB, Tian X, Browning BL, Das S, Emde AK, Clarke WE, Loesch DP, Shetty AC, Blackwell TW, Smith AV, Wong Q, Liu X, Conomos MP, Bobo DM, Aguet F, Albert C, Alonso A, Ardlie KG, Arking DE, Aslibekyan S, Auer PL, Barnard J, Barr RG, Barwick L, Becker LC, Beer RL, Benjamin EJ, Bielak LF, Blangero J, Boehnke M, Bowden DW, Brody JA, Burchard EG, Cade BE, Casella JF, Chalazan B, Chasman DI, Chen YI, Cho MH, Choi SH, Chung MK, Clish CB, Correa A, Curran JE, Custer B, Darbar D, Daya M, de Andrade M, DeMeo DL, Dutcher SK, Ellinor PT, Emery LS, Eng C, Fatkin D, Fingerlin T, Forer L, Fornage M, Franceschini N, Fuchsberger C, Fullerton SM, Germer S, Gladwin MT, Gottlieb DJ, Guo X, Hall ME, He J, Heard-Costa NL, Heckbert SR, Irvin MR, Johnsen JM, Johnson AD, Kaplan R, Kardia SLR, Kelly T, Kelly S, Kenny EE, Kiel DP, Klemmer R, Konkle BA, Kooperberg C, Köttgen A, Lange LA, Lasky-Su J, Levy D, Lin X, Lin KH, Liu C, Loos RJF, Garman L, Gerszten R, Lubitz SA, Lunetta KL, Mak ACY, Manichaikul A, Manning AK, Mathias RA, McManus DD, McGarvey ST, Meigs JB, Meyers DA, Mikulla JL, Minear MA, Mitchell BD, Mohanty S, Montasser ME, Montgomery C, Morrison AC, Murabito JM, Natale A, Natarajan P, Nelson SC, North KE, O'Connell JR, Palmer ND, Pankratz N, Peloso GM, Peyser PA, Pleiness J, Post WS, Psaty BM, Rao DC, Redline S, Reiner AP, Roden D, Rotter JI, Ruczinski I, Sarnowski C, Schoenherr S, Schwartz DA, Seo JS, Seshadri S, Sheehan VA, Sheu WH, Shoemaker MB, Smith NL, Smith JA, Sotoodehnia N, Stilp AM, Tang W, Taylor KD, Telen M, Thornton TA, Tracy RP, Van Den Berg DJ, Vasan RS, Viaud-Martinez KA, Vrieze S, Weeks DE, Weir BS, Weiss ST, Weng LC, Willer CJ, Zhang Y, Zhao X, Arnett DK, Ashley-Koch AE, Barnes KC, Boerwinkle E, Gabriel S, Gibbs R, Rice KM, Rich SS, Silverman EK, Qasba P, Gan W, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Papanicolaou GJ, Nickerson DA, Browning SR, Zody MC, Zöllner S, Wilson JG, Cupples LA, Laurie CC, Jaquish CE, Hernandez RD, O'Connor TD, Abecasis GR.) Nature. 2021 02;590(7845):290-299 PMID: 33568819 PMCID: PMC7875770 SCOPUS ID: 2-s2.0-85101000110 02/12/2021

  • Genome sequencing unveils a regulatory landscape of platelet reactivity

    (Keramati AR, Chen MH, Rodriguez BAT, Yanek LR, Bhan A, Gaynor BJ, Ryan K, Brody JA, Zhong X, Wei Q, Abe N, Abecasis G, Aguet F, Albert C, Almasy L, Alonso A, Ament S, Anderson P, Anugu P, Applebaum-Bowden D, Ardlie K, Arking D, Arnett DK, Ashley-Koch A, Aslibekyan S, Assimes T, Auer P, Avramopoulos D, Ayas N, Balasubramanian A, Barnard J, Barnes K, Barr RG, Barron-Casella E, Barwick L, Beaty T, Beck G, Becker D, Becker L, Beer R, Beitelshees A, Benjamin E, Benos T, Bezerra M, Bielak L, Bis J, Blackwell T, Blangero J, Boerwinkle E, Bowden DW, Bowler R, Brody J, Broeckel U, Broome J, Brown D, Bunting K, Burchard E, Bustamante C, Buth E, Cade B, Cardwell J, Carey V, Carrier J, Carty C, Casaburi R, Romero JPC, Casella J, Castaldi P, Chaffin M, Chang C, Chang YC, Chasman D, Chavan S, Chen BJ, Chen WM, Chen YDI, Cho M, Choi SH, Chuang LM, Chung M, Chung RH, Clish C, Comhair S, Conomos M, Cornell E, Correa A, Crandall C, Crapo J, Cupples LA, Curran J, Curtis J, Custer B, Damcott C, Darbar D, David S, Davis C, Daya M, de Andrade M, Fuentes Ldl, de Vries P.) Nature Communications. December 2021;12(1) SCOPUS ID: 2-s2.0-85108227070 12/01/2021

  • Whole-Exome Sequencing and hiPSC Cardiomyocyte Models Identify MYRIP, TRAPPC11, and SLC27A6 of Potential Importance to Left Ventricular Hypertrophy in an African Ancestry Population.

    (Irvin MR, Aggarwal P, Claas SA, de Las Fuentes L, Do AN, Gu CC, Matter A, Olson BS, Patki A, Schwander K, Smith JD, Srinivasasainagendra V, Tiwari HK, Turner AJ, Nickerson DA, Rao DC, Broeckel U, Arnett DK.) Front Genet. 2021;12:588452 PMID: 33679876 PMCID: PMC7933688 03/09/2021

  • Personal DNA testing increases pharmacy students’ confidence and competence in pharmacogenomics

    (Assem M, Broeckel U, Mackinnon GE.) American Journal of Pharmaceutical Education. 2021;85(4):281-287 SCOPUS ID: 2-s2.0-85104754005 01/01/2021

  • Inherited causes of clonal haematopoiesis in 97,691 whole genomes.

    (Bick AG, Weinstock JS, Nandakumar SK, Fulco CP, Bao EL, Zekavat SM, Szeto MD, Liao X, Leventhal MJ, Nasser J, Chang K, Laurie C, Burugula BB, Gibson CJ, Lin AE, Taub MA, Aguet F, Ardlie K, Mitchell BD, Barnes KC, Moscati A, Fornage M, Redline S, Psaty BM, Silverman EK, Weiss ST, Palmer ND, Vasan RS, Burchard EG, Kardia SLR, He J, Kaplan RC, Smith NL, Arnett DK, Schwartz DA, Correa A, de Andrade M, Guo X, Konkle BA, Custer B, Peralta JM, Gui H, Meyers DA, McGarvey ST, Chen IY, Shoemaker MB, Peyser PA, Broome JG, Gogarten SM, Wang FF, Wong Q, Montasser ME, Daya M, Kenny EE, North KE, Launer LJ, Cade BE, Bis JC, Cho MH, Lasky-Su J, Bowden DW, Cupples LA, Mak ACY, Becker LC, Smith JA, Kelly TN, Aslibekyan S, Heckbert SR, Tiwari HK, Yang IV, Heit JA, Lubitz SA, Johnsen JM, Curran JE, Wenzel SE, Weeks DE, Rao DC, Darbar D, Moon JY, Tracy RP, Buth EJ, Rafaels N, Loos RJF, Durda P, Liu Y, Hou L, Lee J, Kachroo P, Freedman BI, Levy D, Bielak LF, Hixson JE, Floyd JS, Whitsel EA, Ellinor PT, Irvin MR, Fingerlin TE, Raffield LM, Armasu SM, Wheeler MM, Sabino EC, Blangero J, Williams LK, Levy BD, Sheu WH, Roden DM, Boerwinkle E, Manson JE, Mathias RA, Desai P, Taylor KD, Johnson AD, NHLBI Trans-Omics for Precision Medicine Consortium, Auer PL, Kooperberg C, Laurie CC, Blackwell TW, Smith AV, Zhao H, Lange E, Lange L, Rich SS, Rotter JI, Wilson JG, Scheet P, Kitzman JO, Lander ES, Engreitz JM, Ebert BL, Reiner AP, Jaiswal S, Abecasis G, Sankaran VG, Kathiresan S, Natarajan P.) Nature. 2020 10;586(7831):763-768 PMID: 33057201 PMCID: PMC7944936 SCOPUS ID: 2-s2.0-85092548094 10/16/2020

  • Detecting fitness epistasis in recently admixed populations with genome-wide data.

    (Ni X, Zhou M, Wang H, He KY, Broeckel U, Hanis C, Kardia S, Redline S, Cooper RS, Tang H, Zhu X.) BMC Genomics. 2020 Jul 11;21(1):476 PMID: 32652930 PMCID: PMC7353720 SCOPUS ID: 2-s2.0-85087904658 07/13/2020