Lei Wei, PhD
Lei Wei, PhD
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Background
Next-Generation Sequencing (NGS) provides a revolutionary platform in identifying tumorigenic events, whereas data analysis remains as a challenge. We focus on the development and application of NGS programs that accurately detect genomic alterations for cancer research and clinical application.
Our main approach is to perform intergrative analyses of large-scale, multi-dimentional data to unveal the molecular mechanism of disease initiation, progression and prognosis. Most commonly by using Whole Genome Sequencing (WGS) or Whole Exome Sequencing (WES), we are capable of performing genome wide detection of somatic acquired mutations, and inherited germline variants. Further analyses of recurring mutations will help reveal commonly shared mutations in the same cohort. Transcriptome sequencing (RNASeq) will provide additional insights that helps reveal the mechanism of tumorigenesis.
To understand the process of tumor progression, we will study clonal evolution by comparing multiple tumors from the same patient at multiple time points, and/or look into the heterogeneity inside the same tumor. The dynamic pattern will help identify commonly shared key mutations for tumor maintainance and De Novo mutations that are responsible for relapse.
A key application will be personalized medicine. Compared with traditional methods, NGS-based clinical sequencing provides a much more robust and cost-effective method to exam the entire mutation landscape in the tumor. Accurate characterization of individual tumor profile helps the decision making process, not only in finding more effective treatment, but also help avoid unnecessary risk to the patient.
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Kuhn E, Wu RC, Guan B, Wu G, Zhang J, Wang Y, Song L, Yuan X, Wei L, Roden RB, Kuo KT, Nakayama K, Clarke B, Shaw P, Olvera N, Kurman RJ, Levine DA, Wang TL, Shih IeM. Identification of molecular pathway aberrations in uterine serous carcinoma by genome-wide analyses. J Natl Cancer Inst 2012; 104(19):1503-1513. PMID: 22923510
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Holmfeldt L*, Wei L*, Diaz-Flores E, Walsh M, Zhang J, Ding L, Payne-Turner D, Churchman M, Andersson A, Chen SC, McCastlain K, Becksfort J, Ma J, Wu G, Patel SN, Heatley SL, Phillips LA, Song G, Easton J, Parker M, Chen X, Rusch M, Boggs K, Vadodaria B, Hedlund E, Drenberg C, Baker S, Pei D, Cheng C, Huether R, Lu C, Fulton RS, Fulton LL, Tabib Y, Dooling DJ, Ochoa K, Minden M, Lewis ID, To LB, Marlton P, Roberts AW, Raca G, Stock W, Neale G, Drexler HG, Dickins RA, Ellison DW, Shurtleff SA, Pui CH, Ribeiro RC, Devidas M, Carroll AJ, Heerema NA, Wood B, Borowitz MJ, Gastier-Foster JM, Raimondi SC, Mardis ER, Wilson RK, Downing JR, Hunger SP, Loh ML, Mullighan CG. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nature Genetics 2013; 45(3):242-252. PMID: 23334668 (*co-first authors)
Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I, Boop FA, Lu C, Kandoth C, Ding L, Lee R, Huether R, Chen X, Hedlund E, Nagahawatte P, Rusch M, Boggs K, Cheng J, Becksfort J, Ma J, Song G, Li Y, Wei L, Wang J, Shurtleff S, Easton J, Zhao D, Fulton RS, Fulton LL, Dooling DJ, Vadodaria B, Mulder HL, Tang C, Ochoa K, Mullighan CG, Gajjar A, Kriwacki R, Sheer D, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Baker SJ, Ellison DW, The St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat Genet 2013; 45(6):602-612. PMID: 23583981
Benavente CA, McEvoy JD, Finkelstein D, Wei L, Kang G, Wang YD, Neale G, Ragsdale S, Valentine V, Bahrami A, Temirov J, Pounds S, Zhang J, Dyer MA. Cross-species genomic and epigenomic landscape of retinoblastoma. Oncotarget 2013; 4(6):844-859. PMID: 23765217
Shah S, Schrader KA, Waanders E, Timms AE, Vijai J, Miething C, Wechsler J, Yang J, Hayes J, Klein RJ, Zhang J, Wei L, Wu G, Rusch M, Nagahawatte P, Ma J, Chen SC, Song G, Cheng J, Meyers P, Bhojwani D, Jhanwar S, Maslak P, Fleisher M, Littman J, Offit L, Rau-Murthy R, Fleischut MH, Corines M, Murali R, Gao X, Manschreck C, Kitzing T, Murty VV, Raimondi SC, Kuiper RP, Simons A, Schiffman JD, Onel K, Plon SE, Wheeler DA, Ritter D, Ziegler DS, Tucker K, Sutton R, Chenevix-Trench G, Li J, Huntsman DG, Hansford S, Senz J, Walsh T, Lee M, Hahn CN, Roberts KG, King MC, Lo SM, Levine RL, Viale A, Socci ND, Nathanson KL, Scott HS, Daly M, Lipkin SM, Lowe SW, Downing JR, Altshuler D, Sandlund JT, Horwitz MS, Mullighan CG, Offit K. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia. Nat Genet 2013; 45(10):1226-1231. PMID: 24013638
Jaffe JD, Wang Y, Chan HM, Zhang J, Huether R, Kryukov GV, Bhang HE, Taylor JE, Hu M, Englund NP, Yan F, Wang Z, Robert McDonald E 3rd, Wei L, Ma J, Easton J, Yu Z, Debeaumount R, Gibaja V, Venkatesan K, Schlegel R, Sellers WR, Keen N, Liu J, Caponigro G, Barretina J, Cooke VG, Mullighan C, Carr SA, Downing JR, Garraway LA, Stegmeier F. Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia. Nat Genet 2013; 45(11):138-191. PMCID: PMC4262138
Chen X, Stewart E, Shelat AA, Qu C, Bahrami A, Hatley M, Wu G, Bradley C, McEvoy J, Pappo A, Spunt S, Valentine MB, Valentine V, Krafcik F, Lang WH, Wierdl M, Tsurkan L, Tolleman V, Federico SM, Morton C, Lu C, Ding L, Easton J, Rusch M, Nagahawatte P, Wang J, Parker M, Wei L, Hedlund E, Finkelstein D, Edmonson M, Shurtleff S, Boggs K, Mulder H, Yergeau D, Skapek S, Hawkins DS, Ramirez N, Potter PM, Sandoval JA, Davidoff AM, Mardis ER, Wilson RK, Zhang J, Downing JR, Dyer MA; St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project. Targeting oxidative stress in embryonal rhabdomyosarcoma. Cancer Cell 2013; 24(6):710-724. PMID: 24332040
Chen X, Bahrami A, Pappo A, Easton J, Dalton J, Hedlund E, Ellison D, Shurtleff S, Wu G, Wei L, Parker M, Rusch M, Nagahawatte P, Wu J, Mao S, Boggs K, Mulder H, Yergeau D, Lu C, Ding L, Edmonson M, Qu C, Wang J, Li Y, Navid F, Daw NC, Mardis ER, Wilson RK, Downing JR, Zhang J, Dyer MA; St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project. Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma. Cell Reports 2014; 7(1):104-112. PMCID: PMC4096827
The St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project, Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nature Genetics 2014; 46(5):444-450. PMCID: PMC4056452
Huether R, Dong L, Chen X, Wu G, Parker M, Wei L, Ma J, Edmonson MN, Hedlund EK, Rusch MC, Shurtleff SA, Mulder HL, Boggs K, Vadordaria B, Cheng J, Yergeau D, Song G, Becksfort J, Lemmon G, Weber C, Cai Z, Dang J, Walsh M, Gedman AL, Faber Z, Easton J, Gruber T, Kriwacki RW, Partridge JF, Ding L, Wilson RK, Mardis ER, Mullighan CG, Gilbertson RJ, Baker SJ, Zambetti G, Ellison DW, Zhang J, Downing JR. The landscape of somatic mutations in epigenetic regulators across 1,000 paeddiatric cancer genomes. Nature Communications 2014; 5:3630. PMCID: PMC4119022
Philip NH, Dillon CP, Snyder AG, Fitzgerald P, Wynosky-Dolfi MA, Zwack EE, Hu B, Fitzgerald L, Mauldin EA, Copenhaver AM, Shin S, Wei L, Parker M, Zhang J, Oberst A, Green DR, Brodsky IE. Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-kB and MAPK signaling. Proc Natl Acad Sci U S A 2014; 111(20):7385-7390. PMCID: PMC4034241
Zhu Q, Hu Q, Shepherd L, Wang J, Wei L, Morrison CD, Conroy J, Glenn ST, Davis W, Kwan ML, Ergas IJ, Roh JM, Kushi LH, Ambrosone CB, Liu S, Yao S. The Impact of DNA Input Amount and DNA Source on the Performance of Whole-Exome Sequencing in Cancer Epidemiology. Cancer Epidemiol Biomarkers Prev 2015; May 19. pii: cebp.0205.2015. PMID: 25990554
Dang J*, Wei L*, de Ridder J, Su X, Rust AG, Roberts KG, Payne-Turner D, Cheng J, Ma J, Qu C, Wu G, Song G, Huether RG, Schulman B, Janke L, Zhang J, Downing JR, van der Weyden L, Adams DJ, Mullighan CG. Pax5 is a tumor suppressor in mouse mutagenesis models of acute lymphoblastic leukemia. Blood 2015; 125(23):3609-3617. (*co-first). PMCID: PMC4458800
Qin M, Liu B, Conroy JM, Morrison CD, Hu Q, Cheng Y, Murakami M, Odunsi AO, Johnson CS, Wei L, Liu S, Wang J. SCNVSim: somatic copy number variation and structure variation simulator. BMC Bioinformatics. 2015; 16(1):66. PMCID: PMC4349766
Liu B, Conroy JM, Morrison CD, Odunsi AO, Qin M, Wei L, Trump DL, Johnson CS, Liu S, Wang J. Structural variation discovery in the cancer genome using next generation sequencing: computational solutions and perspectives. Oncotarget 2015; 6(8):5477-5489. PMID: 25849937
Andersson AK, Ma J, Wang J, Chen X, Gedman AL, Dang J, Nakitandwe J, Holmfeldt L, Parker M, Easton J, Huether R, Kriwacki R, Rusch M, Wu G, Li Y, Mulder H, Raimondi S, Pounds S, Kang G, Shi L, Becksfort J, Gupta P, Payne-Turner D, Vadodaria B, Boggs K, Yergeau D, Manne J, Song G, Edmonson M, Nagahawatte P, Wei L, Cheng C, Pei D, Sutton R, Venn NC, Chetcuti A, Rush A, Catchpoole D, Heldrup J, Fioretos T, Lu C, Ding L, Pui CH, Shurtleff S, Mullighan CG, Mardis ER, Wilson RK, Gruber TA, Zhang J, Downing JR; for The St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. Nature Genetics 2015; 47(4):330-337. PMID: 25730765