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    John Landers PhD

    TitleAssociate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentNeurology
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB
    Worcester MA 01605
    Phone508-856-6221
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentNeuroscience

        Overview 
        Narrative

        Biography:

        1986-1990B.S. Rensselaer Polytechnic Institute

        1990-1995Ph.D. University of Pennsylvania

        1995-1997Postdoctoral Research Associate Massachusetts Institute of Technology

        1997-1999Postdoctoral Research Fellow Massachusetts Institute of Technology

        1999-2005Vice President & Chief Scientific OfficerPolyGenyx, Inc.

        2003-2008Assistant Professor of Neurology Harvard Medical School, MGH

        2003-Director of ALS Genetics Day Neuromuscular Research Laboratory

        2008-Associate Professor of Neurology UMASSMedical School

        Research Description:

        Genetics of Familial and Sporadic ALS

        Landers

        Amyotrophic lateral sclerosis (ALS) is a uniformly lethal, age-dependent neurodegenerative disorder with a typical survival of 2 to 5 years. Our laboratory is focused on using high-throughput genomic technologies to identify the genes involved in the development of sporadic and familial ALS. Most recently, our lab has utilized high-density SNP arrays to analyze over 300,000 DNA polymorphisms within ~4,000 subjects to test for their association to sporadic ALS. Through our efforts, we have identified KIFAP3, a kinesin II complex member responsible for fast anterograde axonal transport, as a modifier of survival in sporadic ALS. Homozygotes for the favorable allele located in the promoter region of KIFAP3 display a survival advantage of 14.0 months, a substantial increment (~30%) in this disease. Currently, our efforts are focused on understanding how KIFAP3 influences survival and how we can use this information to aid in the development of strategies to extend the lifespan of ALS patients.



        Rotation Projects

        Rotation Projects:

        1. Characterization of gene which influences survival in sporadic ALS patients.
        2. Characterization of 2 newly identified familial ALS genes.
        3. Development of a new mouse model for familial ALS.
        4. Positional cloning of novel genes which cause familial ALS.



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Calini D, Corrado L, Del Bo R, Gagliardi S, Pensato V, Verde F, Corti S, Mazzini L, Milani P, Castellotti B, Bertolin C, Sorarù G, Cereda C, Comi GP, D'Alfonso S, Gellera C, Ticozzi N, Landers JE, Ratti A, Silani V. Analysis of hnRNPA1, A2/B1, and A3 genes in patients with amyotrophic lateral sclerosis. Neurobiol Aging. 2013 Nov; 34(11):2695.e11-2.
          View in: PubMed
        2. Deng M, Wei L, Zuo X, Tian Y, Xie F, Hu P, Zhu C, Yu F, Meng Y, Wang H, Zhang F, Ma H, Ye R, Cheng H, Du J, Dong W, Zhou S, Wang C, Wang Y, Wang J, Chen X, Sun Z, Zhou N, Jiang Y, Liu X, Li X, Zhang N, Liu N, Guan Y, Han Y, Han Y, Lv X, Fu Y, Yu H, Xi C, Xie D, Zhao Q, Xie P, Wang X, Zhang Z, Shen L, Cui Y, Yin X, Cheng H, Liang B, Zheng X, Lee TM, Chen G, Zhou F, Veldink JH, Robberecht W, Landers JE, Andersen PM, Al-Chalabi A, Shaw C, Liu C, Tang B, Xiao S, Robertson J, Zhang F, van den Berg LH, Sun L, Liu J, Yang S, Ju X, Wang K, Zhang X. Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis. Nat Genet. 2013 Apr 28; 45(6):697-700.
          View in: PubMed
        3. van Blitterswijk M, Wang ET, Friedman BA, Keagle PJ, Lowe P, Leclerc AL, van den Berg LH, Housman DE, Veldink JH, Landers JE. Characterization of FUS Mutations in Amyotrophic Lateral Sclerosis Using RNA-Seq. PLoS One. 2013; 8(4):e60788.
          View in: PubMed
        4. Li S, Sheng J, Hu JK, Yu W, Kishikawa H, Hu MG, Shima K, Wu D, Xu Z, Xin W, Sims KB, Landers JE, Brown RH, Hu GF. Ribonuclease 4 protects neuron degeneration by promoting angiogenesis, neurogenesis, and neuronal survival under stress. Angiogenesis. 2013 Apr; 16(2):387-404.
          View in: PubMed
        5. Ingre C, Landers JE, Rizik N, Volk AE, Akimoto C, Birve A, Hübers A, Keagle PJ, Piotrowska K, Press R, Andersen PM, Ludolph AC, Weishaupt JH. A novel phosphorylation site mutation in profilin 1 revealed in a large screen of US, Nordic, and German amyotrophic lateral sclerosis/frontotemporal dementia cohorts. Neurobiol Aging. 2013 Jun; 34(6):1708.e1-6.
          View in: PubMed
        6. Tiloca C, Ticozzi N, Pensato V, Corrado L, Del Bo R, Bertolin C, Fenoglio C, Gagliardi S, Calini D, Lauria G, Castellotti B, Bagarotti A, Corti S, Galimberti D, Cagnin A, Gabelli C, Ranieri M, Ceroni M, Siciliano G, Mazzini L, Cereda C, Scarpini E, Sorarù G, Comi GP, D'Alfonso S, Gellera C, Ratti A, Landers JE, Silani V. Screening of the PFN1 gene in sporadic amyotrophic lateral sclerosis and in frontotemporal dementia. Neurobiol Aging. 2013 May; 34(5):1517.e9-1517.e10.
          View in: PubMed
        7. Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1. Neurobiol Aging. 2013 Jan; 34(1):357.e7-19.
          View in: PubMed
        8. Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron DM, Kost JE, Gonzalez-Perez P, Fox AD, Adams J, Taroni F, Tiloca C, Leclerc AL, Chafe SC, Mangroo D, Moore MJ, Zitzewitz JA, Xu ZS, van den Berg LH, Glass JD, Siciliano G, Cirulli ET, Goldstein DB, Salachas F, Meininger V, Rossoll W, Ratti A, Gellera C, Bosco DA, Bassell GJ, Silani V, Drory VE, Brown RH, Landers JE. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature. 2012 Aug 22; 488(7412):499-503.
          View in: PubMed
        9. Diekstra FP, Saris CG, van Rheenen W, Franke L, Jansen RC, van Es MA, van Vught PW, Blauw HM, Groen EJ, Horvath S, Estrada K, Rivadeneira F, Hofman A, Uitterlinden AG, Robberecht W, Andersen PM, Melki J, Meininger V, Hardiman O, Landers JE, Brown RH, Shatunov A, Shaw CE, Leigh PN, Al-Chalabi A, Ophoff RA, van den Berg LH, Veldink JH. Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS. PLoS One. 2012; 7(4):e35333.
          View in: PubMed
        10. Ramos EM, Keagle P, Gillis T, Lowe P, Mysore JS, Leclerc AL, Ratti A, Ticozzi N, Gellera C, Gusella JF, Silani V, Alonso I, Brown RH, Macdonald ME, Landers JE. Prevalence of Huntington's disease gene CAG repeat alleles in sporadic amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler. 2012 May; 13(3):265-9.
          View in: PubMed
        11. van Es MA, Schelhaas HJ, van Vught PW, Ticozzi N, Andersen PM, Groen EJ, Schulte C, Blauw HM, Koppers M, Diekstra FP, Fumoto K, Leclerc AL, Keagle P, Bloem BR, Scheffer H, van Nuenen BF, van Blitterswijk M, van Rheenen W, Wills AM, Lowe PP, Hu GF, Yu W, Kishikawa H, Wu D, Folkerth RD, Mariani C, Goldwurm S, Pezzoli G, Van Damme P, Lemmens R, Dahlberg C, Birve A, Fernández-Santiago R, Waibel S, Klein C, Weber M, van der Kooi AJ, de Visser M, Verbaan D, van Hilten JJ, Heutink P, Hennekam EA, Cuppen E, Berg D, Brown RH, Silani V, Gasser T, Ludolph AC, Robberecht W, Ophoff RA, Veldink JH, Pasterkamp RJ, de Bakker PI, Landers JE, van de Warrenburg BP, van den Berg LH. Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis. Ann Neurol. 2011 Dec; 70(6):964-73.
          View in: PubMed
        12. Duff RM, Tay V, Hackman P, Ravenscroft G, McLean C, Kennedy P, Steinbach A, Schöffler W, van der Ven PF, Fürst DO, Song J, Djinovic-Carugo K, Penttilä S, Raheem O, Reardon K, Malandrini A, Gambelli S, Villanova M, Nowak KJ, Williams DR, Landers JE, Brown RH, Udd B, Laing NG. Mutations in the N-terminal Actin-Binding Domain of Filamin C Cause a Distal Myopathy. Am J Hum Genet. 2011 Jun 10; 88(6):729-40.
          View in: PubMed
        13. Bosco DA, Landers JE. Genetic determinants of amyotrophic lateral sclerosis as therapeutic targets. CNS Neurol Disord Drug Targets. 2010 Dec; 9(6):779-90.
          View in: PubMed
        14. Shatunov A, Mok K, Newhouse S, Weale ME, Smith B, Vance C, Johnson L, Veldink JH, van Es MA, van den Berg LH, Robberecht W, Van Damme P, Hardiman O, Farmer AE, Lewis CM, Butler AW, Abel O, Andersen PM, Fogh I, Silani V, Chiò A, Traynor BJ, Melki J, Meininger V, Landers JE, McGuffin P, Glass JD, Pall H, Leigh PN, Hardy J, Brown RH, Powell JF, Orrell RW, Morrison KE, Shaw PJ, Shaw CE, Al-Chalabi A. Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study. Lancet Neurol. 2010 Oct; 9(10):986-94.
          View in: PubMed
        15. Blauw HM, Al-Chalabi A, Andersen PM, van Vught PW, Diekstra FP, van Es MA, Saris CG, Groen EJ, van Rheenen W, Koppers M, Van't Slot R, Strengman E, Estrada K, Rivadeneira F, Hofman A, Uitterlinden AG, Kiemeney LA, Vermeulen SH, Birve A, Waibel S, Meyer T, Cronin S, McLaughlin RL, Hardiman O, Sapp PC, Tobin MD, Wain LV, Tomik B, Slowik A, Lemmens R, Rujescu D, Schulte C, Gasser T, Brown RH, Landers JE, Robberecht W, Ludolph AC, Ophoff RA, Veldink JH, van den Berg LH. A large genome scan for rare CNVs in amyotrophic lateral sclerosis. Hum Mol Genet. 2010 Oct 15; 19(20):4091-9.
          View in: PubMed
        16. Ticozzi N, LeClerc AL, Keagle PJ, Glass JD, Wills AM, van Blitterswijk M, Bosco DA, Rodriguez-Leyva I, Gellera C, Ratti A, Taroni F, McKenna-Yasek D, Sapp PC, Silani V, Furlong CE, Brown RH, Landers JE. Paraoxonase gene mutations in amyotrophic lateral sclerosis. Ann Neurol. 2010 Jul; 68(1):102-7.
          View in: PubMed
        17. Bogaert E, Goris A, Van Damme P, Geelen V, Lemmens R, van Es MA, van den Berg LH, Sleegers K, Verpoorten N, Timmerman V, De Jonghe P, Van Broeckhoven C, Traynor BJ, Landers JE, Brown RH, Glass JD, Al-Chalabi A, Shaw CE, Birve A, Andersen PM, Slowik A, Tomik B, Melki J, Robberecht W, Van Den Bosch L. Polymorphisms in the GluR2 gene are not associated with amyotrophic lateral sclerosis. Neurobiol Aging. 2012 Feb; 33(2):418-20.
          View in: PubMed
        18. van Blitterswijk M, Landers JE. RNA processing pathways in amyotrophic lateral sclerosis. Neurogenetics. 2010 Jul; 11(3):275-90.
          View in: PubMed
        19. Ticozzi N, Leclerc AL, van Blitterswijk M, Keagle P, McKenna-Yasek DM, Sapp PC, Silani V, Wills AM, Brown RH, Landers JE. Mutational analysis of TARDBP in neurodegenerative diseases. Neurobiol Aging. 2011 Nov; 32(11):2096-9.
          View in: PubMed
        20. Wain LV, Pedroso I, Landers JE, Breen G, Shaw CE, Leigh PN, Brown RH, Tobin MD, Al-Chalabi A. The role of copy number variation in susceptibility to amyotrophic lateral sclerosis: genome-wide association study and comparison with published loci. PLoS One. 2009; 4(12):e8175.
          View in: PubMed
        21. van Es MA, Veldink JH, Saris CG, Blauw HM, van Vught PW, Birve A, Lemmens R, Schelhaas HJ, Groen EJ, Huisman MH, van der Kooi AJ, de Visser M, Dahlberg C, Estrada K, Rivadeneira F, Hofman A, Zwarts MJ, van Doormaal PT, Rujescu D, Strengman E, Giegling I, Muglia P, Tomik B, Slowik A, Uitterlinden AG, Hendrich C, Waibel S, Meyer T, Ludolph AC, Glass JD, Purcell S, Cichon S, Nöthen MM, Wichmann HE, Schreiber S, Vermeulen SH, Kiemeney LA, Wokke JH, Cronin S, McLaughlin RL, Hardiman O, Fumoto K, Pasterkamp RJ, Meininger V, Melki J, Leigh PN, Shaw CE, Landers JE, Al-Chalabi A, Brown RH, Robberecht W, Andersen PM, Ophoff RA, van den Berg LH. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nat Genet. 2009 Oct; 41(10):1083-7.
          View in: PubMed
        22. Broom WJ, Johnson DV, Garber M, Andersen PM, Lennon N, Landers J, Nusbaum C, Russ C, Brown RH. DNA sequence analysis of the conserved region around the SOD1 gene locus in recessively inherited ALS. Neurosci Lett. 2009 Sep 29; 463(1):64-9.
          View in: PubMed
        23. Landers JE, Melki J, Meininger V, Glass JD, van den Berg LH, van Es MA, Sapp PC, van Vught PW, McKenna-Yasek DM, Blauw HM, Cho TJ, Polak M, Shi L, Wills AM, Broom WJ, Ticozzi N, Silani V, Ozoguz A, Rodriguez-Leyva I, Veldink JH, Ivinson AJ, Saris CG, Hosler BA, Barnes-Nessa A, Couture N, Wokke JH, Kwiatkowski TJ, Ophoff RA, Cronin S, Hardiman O, Diekstra FP, Leigh PN, Shaw CE, Simpson CL, Hansen VK, Powell JF, Corcia P, Salachas F, Heath S, Galan P, Georges F, Horvitz HR, Lathrop M, Purcell S, Al-Chalabi A, Brown RH. Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2009 Jun 2; 106(22):9004-9.
          View in: PubMed
        24. Shi L, Landers JE. High-throughput mutation screening using a single amplification condition. Methods Mol Biol. 2009; 520:195-204.
          View in: PubMed
        25. Chow CY, Landers JE, Bergren SK, Sapp PC, Grant AE, Jones JM, Everett L, Lenk GM, McKenna-Yasek DM, Weisman LS, Figlewicz D, Brown RH, Meisler MH. Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. Am J Hum Genet. 2009 Jan; 84(1):85-8.
          View in: PubMed
        26. Simpson CL, Lemmens R, Miskiewicz K, Broom WJ, Hansen VK, van Vught PW, Landers JE, Sapp P, Van Den Bosch L, Knight J, Neale BM, Turner MR, Veldink JH, Ophoff RA, Tripathi VB, Beleza A, Shah MN, Proitsi P, Van Hoecke A, Carmeliet P, Horvitz HR, Leigh PN, Shaw CE, van den Berg LH, Sham PC, Powell JF, Verstreken P, Brown RH, Robberecht W, Al-Chalabi A. Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration. Hum Mol Genet. 2009 Feb 1; 18(3):472-81.
          View in: PubMed
        27. Landers JE, Shi L, Cho TJ, Glass JD, Shaw CE, Leigh PN, Diekstra F, Polak M, Rodriguez-Leyva I, Niemann S, Traynor BJ, McKenna-Yasek D, Sapp PC, Al-Chalabi A, Wills AM, Brown RH. A common haplotype within the PON1 promoter region is associated with sporadic ALS. Amyotroph Lateral Scler. 2008 Oct; 9(5):306-14.
          View in: PubMed
        28. Jordan B, Charest A, Dowd JF, Blumenstiel JP, Yeh Rf RF, Osman A, Housman DE, Landers JE. Genome complexity reduction for SNP genotyping analysis. Proc Natl Acad Sci U S A. 2002 Mar 5; 99(5):2942-7.
          View in: PubMed
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