Laufey Amundadottir, Ph.D.
Laboratory of Translational Genomics
9609 Medical Center Drive
Rockville, MD 20850
Major advances have occurred in the last few years in our understanding of the genetics of common diseases. Genome-wide association studies, which assess hundreds of thousands of single nucleotide polymorphisms (SNPs) in large cohort and case-control studies, have provided new insights into the inherited factors that contribute to risk of developing cancer. These efforts have led to the discovery of thousands of chromosomal loci that significantly associate with one or more complex diseases or traits, including cancer. However, for most of the identified loci, the elucidation of the functional basis underlying disease risk is in the very early stages. This interface between gene mapping approaches and the function of risk variants is of special interest to my laboratory.
Gene Mapping in Pancreatic Cancer
Dr. Amundadottir co-leads PanScan, a GWAS of pancreatic cancer conducted within the framework of the NCI-sponsored Cohort Consortium. Collaborative efforts are conducted with the Pancreatic Cancer Case Control Consortium (PanC4), the PANcreatic Disease ReseArch (PANDoRA) consortium, the European Study on Pancreatic Cancer Genetics and Epidemology (PanGen-EU), and Chinese and Japanese pancreatic cancer GWAS efforts. The aim of these large international studies is to identify genetic factors that contribute to the risk of pancreatic cancer. Four GWAS phases have already been performed in close to 12,000 case and 17,000 control subjects from over 30 cohort and case-control studies from the U.S., Europe and Asia. This work has resulted in the discovery of fourteen common susceptibility loci for pancreatic cancer on chromosomes 1q32.1 (NR5A2, two independent loci), 2p14 (ETAA1), 3q28 (TP63), 5p15.33 (three independent risk loci in the TERT-CLPTM1L region), 7p14.1 (SUGCT), 7q23.2 (LINC-PINT), 8q24.1 (MYC/PVT1 region, two independent loci), 9q34.2 (ABO), 13q12.2 (PDX1), 13q22.1 (nongenic), 16q23.1 (BCAR1/CTRB1/CTRB2), 17q24.3 (LINC00673) and 22q12.1 (ZNRF3). Further GWAS phases, as well as studies that aim at uncovering less common and rare pancreatic cancer risk variants, are underway.
Functional Characterization of Pancreatic Cancer Risk Loci
My laboratory conducts fine-mapping of risk loci identified in PanScan and collaborative gene mapping efforts, as well as wet-lab studies to uncover functional variants at each locus and understand the mechanism by which they influence risk of pancreatic cancer. This work involves genomic and epigenomic approaches, with a focus on genome-wide expression quantitative trait locus (eQTL) analyses to investigate the genetics of gene expression in normal and tumor derived pancreatic tissue samples and correlate to pancreatic cancer risk alleles as well as Transcriptome Wide Association Studies (TWAS) for gene mapping. These transcriptome and epigenome datasets are generated in our laboratory and supplemented with publicly available datasets. Furthermore, my laboratory focuses on targeted functional analyses in specific pancreatic cancer susceptibility loci. This work includes analysis of gene expression in the vicinity of risk variants, investigation of transcriptional regulation and gene/protein function with the aim of connecting pancreatic cancer risk variants to target genes and molecular phenotypes to explain the underlying biology of the risk at each locus.
Dr. Amundadottir received a Ph.D. in cell biology in 1995 from Georgetown University in Washington, D.C. She conducted her postdoctoral training with Dr. Phil Leder in the Department of Genetics at Harvard Medical School in Boston, Massachusetts, then joined deCODE Genetics in Iceland in 1998 as the head of the Division of Cancer Genetics, where she led genome-wide linkage and association efforts in various cancers. Dr. Amundadottir joined the NCI in 2007 as a senior scientist and became a tenure-track investigator in the Laboratory of Translational Genomics in 2008. She received NIH scientific tenure and was promoted to senior investigator in 2017. Her work focuses on genome-wide association studies (GWAS) and other gene mapping approaches to identify germline variants associated with risk of pancreatic cancer and the functional approaches required to understand the biological mechanisms by which they influence risk of pancreatic cancer.
Jia J, Parikh H, Xiao W, Hoskins JW, Pflicke H, Liu X, Collins I, Zhou W, Wang Z, Powell J, Thorgeirsson SS, Rudloff U, Petersen GM, Amundadottir LT. An integrated transcriptome and epigenome analysis identifies a novel candidate gene for pancreatic cancer. BMC Med Genomics. 2013;6:33.
Wang Z, Zhu B, Zhang M, Parikh H, Jia J, Chung CC, Sampson JN, Hoskins JW, Hutchinson A, Burdette L, Ibrahim A, Hautman C, Raj PS, Abnet CC, Adjei AA, Ahlbom A, Albanes D, Allen NE, Ambrosone CB, Aldrich M, Amiano P, Amos C, Andersson U, Andriole G Jr, Andrulis IL, Arici C, Arslan AA, Austin MA, Baris D, Barkauskas DA, Bassig BA, Beane Freeman LE, Berg CD, Berndt SI, Bertazzi PA, Biritwum RB, Black A, Blot W, Boeing H, Boffetta P, Bolton K, Boutron-Ruault MC, Bracci PM, Brennan P, Brinton LA, Brotzman M, Bueno-de-Mesquita HB, Buring JE, Butler MA, Cai Q, Cancel-Tassin G, Canzian F, Cao G, Caporaso NE, Carrato A, Carreon T, Carta A, Chang GC, Chang IS, Chang-Claude J, Che X, Chen CJ, Chen CY, Chen CH, Chen C, Chen KY, Chen YM, Chokkalingam AP, Chu LW, Clavel-Chapelon F, Colditz GA, Colt JS, Conti D, Cook MB, Cortessis VK, Crawford ED, Cussenot O, Davis FG, De Vivo I, Deng X, Ding T, Dinney CP, Di Stefano AL, Diver WR, Duell EJ, Elena JW, Fan JH, Feigelson HS, Feychting M, Figueroa JD, Flanagan AM, Fraumeni JF Jr, Freedman ND, Fridley BL, Fuchs CS, Gago-Dominguez M, Gallinger S, Gao YT, Gapstur SM, Garcia-Closas M, Garcia-Closas R, Gastier-Foster JM, Gaziano JM, Gerhard DS, Giffen CA, Giles GG, Gillanders EM, Giovannucci EL, Goggins M, Gokgoz N, Goldstein AM, Gonzalez C, Gorlick R, Greene MH, Gross M, Grossman HB, Grubb R 3rd, Gu J, Guan P, Haiman CA, Hallmans G, Hankinson SE, Harris CC, Hartge P, Hattinger C, Hayes RB, He Q, Helman L, Henderson BE, Henriksson R, Hoffman-Bolton J, Hohensee C, Holly EA, Hong YC, Hoover RN, Hosgood HD 3rd, Hsiao CF, Hsing AW, Hsiung CA, Hu N, Hu W, Hu Z, Huang MS, Hunter DJ, Inskip PD, Ito H, Jacobs EJ, Jacobs KB, Jenab M, Ji BT, Johansen C, Johansson M, Johnson A, Kaaks R, Kamat AM, Kamineni A, Karagas M, Khanna C, Khaw KT, Kim C, Kim IS, Kim JH, Kim YH, Kim YC, Kim YT, Kang CH, Jung YJ, Kitahara CM, Klein AP, Klein R, Kogevinas M, Koh WP, Kohno T, Kolonel LN, Kooperberg C, Kratz CP, Krogh V, Kunitoh H, Kurtz RC, Kurucu N, Lan Q, Lathrop M, Lau CC, Lecanda F, Lee KM, Lee MP, Le Marchand L, Lerner SP, Li D, Liao LM, Lim WY, Lin D, Lin J, Lindstrom S, Linet MS, Lissowska J, Liu J, Ljungberg B, Lloreta J, Lu D, Ma J, Malats N, Mannisto S, Marina N, Mastrangelo G, Matsuo K, McGlynn KA, McKean-Cowdin R, McNeill LH, McWilliams RR, Melin BS, Meltzer PS, Mensah JE, Miao X, Michaud DS, Mondul AM, Moore LE, Muir K, Niwa S, Olson SH, Orr N, Panico S, Park JY, Patel AV, Patino-Garcia A, Pavanello S, Peeters PH, Peplonska B, Peters U, Petersen GM, Picci P, Pike MC, Porru S, Prescott J, Pu X, Purdue MP, Qiao YL, Rajaraman P, Riboli E, Risch HA, Rodabough RJ, Rothman N, Ruder AM, Ryu JS, Sanson M, Schned A, Schumacher FR, Schwartz AG, Schwartz KL, Schwenn M, Scotlandi K, Seow A, Serra C, Serra M, Sesso HD, Severi G, Shen H, Shen M, Shete S, Shiraishi K, Shu XO, Siddiq A, Sierrasesumaga L, Sierri S, Loon Sihoe AD, Silverman DT, Simon M, Southey MC, Spector L, Spitz M, Stampfer M, Stattin P, Stern MC, Stevens VL, Stolzenberg-Solomon RZ, Stram DO, Strom SS, Su WC, Sund M, Sung SW, Swerdlow A, Tan W, Tanaka H, Tang W, Tang ZZ, Tardon A, Tay E, Taylor PR, Tettey Y, Thomas DM, Tirabosco R, Tjonneland A, Tobias GS, Toro JR, Travis RC, Trichopoulos D, Troisi R, Truelove A, Tsai YH, Tucker MA, Tumino R, Van Den Berg D, Van Den Eeden SK, Vermeulen R, Vineis P, Visvanathan K, Vogel U, Wang C, Wang C, Wang J, Wang SS, Weiderpass E, Weinstein SJ, Wentzensen N, Wheeler W, White E, Wiencke JK, Wolk A, Wolpin BM, Wong MP, Wrensch M, Wu C, Wu T, Wu X, Wu YL, Wunder JS, Xiang YB, Xu J, Yang HP, Yang PC, Yatabe Y, Ye Y, Yeboah ED, Yin Z, Ying C, Yu CJ, Yu K, Yuan JM, Zanetti KA, Zeleniuch-Jacquotte A, Zheng W, Zhou B, Mirabello L, Savage SA, Kraft P, Chanock SJ, Yeager M, Landi MT, Shi J, Chatterjee N, Amundadottir LT. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33. Hum Mol Genet. 2014;23(24):6616-33.
Wolpin BM, Rizzato C, Kraft P, Kooperberg C, Petersen GM, Wang Z, Arslan AA, Beane-Freeman L, Bracci PM, Buring J, Canzian F, Duell EJ, Gallinger S, Giles GG, Goodman GE, Goodman PJ, Jacobs EJ, Kamineni A, Klein AP, Kolonel LN, Kulke MH, Li D, Malats N, Olson SH, Risch HA, Sesso HD, Visvanathan K, White E, Zheng W, Abnet CC, Albanes D, Andreotti G, Austin MA, Barfield R, Basso D, Berndt SI, Boutron-Ruault MC, Brotzman M, Büchler MW, Bueno-de-Mesquita HB, Bugert P, Burdette L, Campa D, Caporaso NE, Capurso G, Chung C, Cotterchio M, Costello E, Elena J, Funel N, Gaziano JM, Giese NA, Giovannucci EL, Goggins M, Gorman MJ, Gross M, Haiman CA, Hassan M, Helzlsouer KJ, Henderson BE, Holly EA, Hu N, Hunter DJ, Innocenti F, Jenab M, Kaaks R, Key TJ, Khaw KT, Klein EA, Kogevinas M, Krogh V, Kupcinskas J, Kurtz RC, LaCroix A, Landi MT, Landi S, Le Marchand L, Mambrini A, Mannisto S, Milne RL, Nakamura Y, Oberg AL, Owzar K, Patel AV, Peeters PH, Peters U, Pezzilli R, Piepoli A, Porta M, Real FX, Riboli E, Rothman N, Scarpa A, Shu XO, Silverman DT, Soucek P, Sund M, Talar-Wojnarowska R, Taylor PR, Theodoropoulos GE, Thornquist M, Tjønneland A, Tobias GS, Trichopoulos D, Vodicka P, Wactawski-Wende J, Wentzensen N, Wu C, Yu H, Yu K, Zeleniuch-Jacquotte A, Hoover R, Hartge P, Fuchs C, Chanock SJ, Stolzenberg-Solomon RS, Amundadottir LT. Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nat Genet. 2014;46(9):994-1000.
Jia J, Bosley AD, Thompson A, Hoskins JW, Cheuk A, Collins I, Parikh H, Xiao Z, Ylaya K, Dzyadyk M, Cozen W, Hernandez BY, Lynch CF, Loncarek J, Altekruse SF, Zhang L, Westlake CJ, Factor VM, Thorgeirsson S, Bamlet WR, Hewitt SM, Petersen GM, Andresson T, Amundadottir LT. CLPTM1L promotes growth and enhances aneuploidy in pancreatic cancer cells. Cancer Res. 2014;74(10):2785-95.
Hoskins JW, Jia J, Flandez M, Parikh H, Xiao W, Collins I, Emmanuel MA, Ibrahim A, Powell J, Zhang L, Malats N, Bamlet WR, Petersen GM, Real FX, Amundadottir LT. Transcriptome analysis of pancreatic cancer reveals a tumor suppressor function for HNF1A. Carcinogenesis. 2014;35(12):2670-8.
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This page was last updated on October 20th, 2020