Lei Wei, PhD
Lei Wei, PhD
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.
Wei L*, Murphy, BL*, Wu G*, Parker M, Easton J, Gilbertson RJ, Zhang J, Roussel MF. Exome sequencing analysis of murine medulloblastoma models identifies Wdr11 as a potential tumor suppressor in Group 3 tumors. Oncotarget. 2017 Jul 27. doi: 10.18632/oncotarget.19642
Zhang J, McCastlain K, Yoshihara H, Xu B, Chang Y, Churchman ML, Wu G, Li Y, Wei L, Iacobucci I, Liu Y, Qu C, Wen J, Edmonson M, Payne-Turner D, Kaufmann KB, Takayanagi SI, Wienholds E, Waanders E, Ntziachristos P, Bakogianni S, Wang J, Aifantis I, Roberts KG, Ma J, Song G, Easton J, Mulder HL, Chen X, Newman S, Ma X, Rusch M, Gupta P, Boggs K, Vadodaria B, Dalton J, Liu Y, Valentine ML, Ding L, Lu C, Fulton RS, Fulton L, Tabib Y, Ochoa K, Devidas M, Pei D, Cheng C, Yang J, Evans WE, Relling MV, Pui CH, Jeha S, Harvey RC, Chen IL, Willman CL, Marcucci G, Bloomfield CD, Kohlschmidt J, Mrózek K, Paietta E, Tallman MS, Stock W, Foster MC, Racevskis J, Rowe JM, Luger S, Kornblau SM, Shurtleff SA, Raimondi SC, Mardis ER, Wilson RK, Dick JE, Hunger SP, Loh ML, Downing JR, Mullighan CG; St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project. Deregulation of DUX4 and ERG in acute lymphoblastic leukemia. Nat Genet. 2016 Dec;48(12):1481-1489. doi: 10.1038/ng.3691.
Wei L*, Chintala S*, Ciamporcero E*, Ramakrishnan S, Elbanna M, Wang J, Hu Q, Glenn ST, Murakami M, Liu L, Cortes Gomez E, Sun Y, Conroy J, Miles KM, Malathi K, Ramaiah S, Anbarasu A, Woloszynska-Read A, Johnson CS, Conroy J, Liu S, Morrison CD, Pili R. Genomic profiling is predictive of response to cisplatin treatment but not to PI3K inhibition in bladder cancer patient-derived xenografts. Oncotarget. 2016 Nov 3. doi: 10.18632/oncotarget.13062.
Wei L*+, Papanicolau-Sengos A*, Liu S*, Wang J*, Conroy JM*, Glenn ST, Brese E, Hu Q, Miles KM, Burgher B, Qin M, Head K, Omilian AR, Bshara W, Krolewski J, Trump DL, Johnson CS, Morrison CD+. Pitfalls of improperly procured adjacent non-neoplastic tissue for somatic mutation analysis using next-generation sequencing. BMC Med Genomics. 2016 Oct 19;9(1):64. (*co-first +co-corresponding)
Wei L*, Wang J* Lampert E, Schlanger S, DePriest AD, Hu Q, Gomez EC, Murakam M, Glenn ST, Conroy J, Morrison C, Azabdaftari G, Mohler JL, Liu S, Heemers HV. Intratumoral and Intertumoral Genomic Heterogeneity of Multifocal Localized Prostate Cancer Impacts Molecular Classifications and Genomic Prognosticators. European Urology. 2016 Jul 20. pii: S0302-2838(16)30406-7. doi: 10.1016/j.eururo.2016.07.008.
Wei L*, Liu S*, Conroy J*, Wang J*, Papanicolau-Sengos A*, Glenn ST, Murakami M, Liu L, Hu Q, Conroy J, Miles KM, Nowak DE, Liu B, Qin M, Bshara W, Omilian AR, Head K, Bianchi M, Burgher B, Darlak C, Kane J, Merzianu M, Cheney R, Fabiano A, Salerno K, Talati C, Khushalani NI, Trump DL, Johnson CS, Morrison CD. Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib. Cold Spring Harb Mol Case Stud. 2015 Oct;1(1):a000380. doi: 10.1101/mcs.a000380.
Wang J, Papanicolau-Sengos A, Chintala S, Wei L, Liu B, Hu Q, Miles KM, Conroy JM, Glenn ST, Costantini M, Magi-Galluzzi C, Signoretti S, Choueiri T, Gallucci M, Sentinelli S, Fazio VM, Poeta ML, Liu S, Morrison C, Pili R. Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation. Oncotarget. 2016 Apr 28. doi: 10.18632/oncotarget.9093.
Ma L, Qin M, Liu B, Hu Q, Wei L, Wang J, Liu S. cnvCurator: an interactive visualization and editing tool for somatic copy number variations. BMC Bioinformatics. 2015 Oct 15;16:331. doi: 10.1186/s12859-015-0766-y.
Wei L*+, Liu LT*, Conroy JR, Hu Q, Conroy JM, Morrison CD, Johnson CS, Wang J, Liu S+. MAC: identifying and correcting annotation for multi-nucleotide variations. BMC Genomics. 2015 Aug 1;16:569. doi: 10.1186/s12864-015-1779-7. (*co-first +co-corresponding)
Zhu 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.
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 Apr 8. pii: blood-2015-02-626127. (*co-first)
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 Feb 28;16(1):66. doi: 10.1186/s12859-015-0502-7.
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 Mar 20;6(8):5477-89.
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 Mar 2. doi: 10.1038/ng.3230.
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-κB and MAPK signaling. Proc Natl Acad Sci U S A. 2014 May 20;111(20):7385-90. doi: 10.1073/pnas.1403252111.
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 paediatric cancer genomes. Nature Communications. 2014 Apr 8;5:3630. doi: 10.1038/ncomms4630.
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 Apr 6. doi: 10.1038/ng.2938.
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 Apr 2. pii: S2211-1247(14)00165-X. doi:10.1016/j.celrep.2014.03.003.
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 Dec 9;24(6):710-24. doi: 10.1016/j.ccr.2013.11.002.
Fu Y, Ding D, Wei L, Jiang H, Salvi R. Ouabain-induced apoptosis in cochlear hair cells and spiral ganglion neurons in vitro. Biomed Res Int. 2013;2013:628064. doi: 10.1155/2013/628064.
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. Nature Genetics. 2013 Nov;45(11):1386-91. doi: 10.1038/ng.2777.
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. Nature Genetics. 2013 Oct;45(10):1226-31. doi: 10.1038/ng.2754.
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 Jun;4(6):844-59.
The St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project, 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. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nature Genetics. 2013 Jun;45(6):602-12. doi: 10.1038/ng.2611.
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 Mar;45(3):242-52. (*co-first)
Hussin J, Sinnett D, Casals F, Idaghdour Y, Bruat V, Saillour V, Healy J, Grenier JC, de Malliard T, Busche S, Spinella JF, Larivière M, Gibson G, Andersson A, Holmfeldt L, Ma J, Wei L, Zhang J, Andelfinger G, Downing JR, Mullighan CG, Awadalla P. Rare allelic forms of PRDM9 associated with childhood leukemogenesis. Genome Research. 2013 Mar;23(3):419-30.
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 IM. Identification of molecular pathway aberrations in uterine serous carcinoma by genome-wide analyses. J Natl Cancer Inst. 2012 Oct 3;104(19):1503-13.
Roberts KG, Morin RD, Zhang J, Hirst M, Zhao Y, Su X, Chen SC, Payne-Turner D, Churchman ML, Harvey RC, Chen X, Kasap C, Yan C, Becksfort J, Finney RP, Teachey DT, Maude SL, Tse K, Moore R, Jones S, Mungall K, Birol I, Edmonson MN, Hu Y, Buetow KE, Chen IM, Carroll WL, Wei L, Ma J, Kleppe M, Levine RL, Garcia-Manero G, Larsen E, Shah NP, Devidas M, Reaman G, Smith M, Paugh SW, Evans WE, Grupp SA, Jeha S, Pui CH, Gerhard DS, Downing JR, Willman CL, Loh M, Hunger SP, Marra MA, Mullighan CG. Novel genetic alterations activating kinase and cytokine receptor signaling in high risk acute lymphoblastic leukemia. Cancer Cell. 2012 Aug 14;22(2):153-66.
Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L, Phoenix TN, Hedlund E, Wei L, Zhu X, Chalhoub N, Baker SJ, Huether R, Kriwacki R, Curley N, Thiruvenkatam R, Wang J, Wu G, Rusch M, Hong X, Becksfort J, Gupta P, Ma J, Easton J, Vadodaria B, Onar-Thomas A, Lin T, Li S, Pounds S, Paugh S, Zhao D, Kawauchi D, Roussel MF, Finkelstein D, Ellison DW, Lau CC, Bouffet E, Hassall T, Gururangan S, Cohn R, Fulton RS, Fulton LL, Dooling DJ, Ochoa K, Gajjar A, Mardis ER, Wilson RK, Downing JR, Zhang J, Gilbertson RJ. Novel mutations target distinct subgroups of medulloblastoma. Nature. 2012 Aug 2;488(7409):43-8.
Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012 Jan 11;481(7380):157-63.
Wang J, Mullighan CG, Easton J, Roberts S, Heatley SL, Ma J, Rusch MC, Chen K, Harris CC, Ding L, Holmfeldt L, Payne-Turner D, Fan X, Wei L, Zhao D, Obenauer JC, Naeve C, Mardis ER, Wilson RK, Downing JR, Zhang J. CREST maps somatic structural variation in cancer genomes with base-pair resolution. Nature Methods. 2011 Jun 12;8(8):652-4.
Wei L, Ding D, Salvi R. Salicylate-induced degeneration of cochlea spiral ganglion neurons-apoptosis signaling. Neuroscience. 2010 Jun 16; 168(1):288-99.
Wei L, Ding D, Sun W, Xu-Friedman MA. Salvi R. Effects of sodium salicylate on spontaneous and evoked spike rate in the dorsal cochlear nucleus. Hearing Research. 2010 Aug; 267(1-2):54-60.