Photo of Christopher A. Walsh,  MD, PhD

Christopher A. Walsh, MD, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2923


christopher.walsh@childrens.harvard.edu

Christopher A. Walsh, MD, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Bullard Professor of Pediatrics and Neurology, Pediatrics, Harvard Medical School
  • Professor, Neurology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our lab is interested in fundamental mechanisms governing development of the cerebral cortex. We are interested in genes that control neuronal proliferation and cell fate selection, and are using positional cloning to identify genes that when mutated cause the human cerebral cortex to be too large or too small. Abnormalities of some of these genes are likely to be quite relevant to human neural tumors. We are also interested in genes that regulate neuronal migration, which provides a genetic system for analyzing cell migration in general.

Publications

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  • D'Gama AM, Geng Y, Couto JA, Martin B, Boyle EA, LaCoursiere CM, Hossain A, Hatem NE, Barry BJ, Kwiatkowski DJ, Vinters HV, Barkovich AJ, Shendure J, Mathern GW, Walsh CA, Poduri A. Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia. Ann Neurol 2015; 77:720-5. PubMed
  • Ahmed MY, Chioza BA, Rajab A, Schmitz-Abe K, Al-Khayat A, Al-Turki S, Baple EL, Patton MA, Al-Memar AY, Hurles ME, Partlow JN, Hill RS, Evrony GD, Servattalab S, Markianos K, Walsh CA, Crosby AH, Mochida GH. Loss of PCLO function underlies pontocerebellar hypoplasia type III. Neurology 2015. PubMed
  • Johnson MB, Wang PP, Atabay KD, Murphy EA, Doan RN, Hecht JL, Walsh CA. Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex. Nat Neurosci 2015. PubMed
  • Murn J, Zarnack K, Yang YJ, Durak O, Murphy EA, Cheloufi S, Gonzalez DM, Teplova M, Curk T, Zuber J, Patel DJ, Ule J, Luscombe NM, Tsai LH, Walsh CA, Shi Y. Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt. Genes Dev 2015; 29:501-12. PubMed
  • Cai X, Evrony GD, Lehmann HS, Elhosary PC, Mehta BK, Poduri A, Walsh CA. Single-cell, genome-wide sequencing identifies clonal somatic copy-number variation in the human brain. Cell Rep 2015; 10:645. PubMed
  • Evrony GD, Lee E, Mehta BK, Benjamini Y, Johnson RM, Cai X, Yang L, Haseley P, Lehmann HS, Park PJ, Walsh CA. Cell lineage analysis in human brain using endogenous retroelements. Neuron 2015; 85:49-59. PubMed
  • Cai X, Evrony GD, Lehmann HS, Elhosary PC, Mehta BK, Poduri A, Walsh CA. Single-Cell, Genome-wide Sequencing Identifies Clonal Somatic Copy-Number Variation in the Human Brain. Cell Rep 2014; 8:1280-9. PubMed
  • Zhang X, Ling J, Barcia G, Jing L, Wu J, Barry BJ, Mochida GH, Hill RS, Weimer JM, Stein Q, Poduri A, Partlow JN, Ville D, Dulac O, Yu TW, Lam AT, Servattalab S, Rodriguez J, Boddaert N, Munnich A, Colleaux L, Zon LI, Söll D, Walsh CA, Nabbout R. Mutations in QARS, Encoding Glutaminyl-tRNA Synthetase, Cause Progressive Microcephaly, Cerebral-Cerebellar Atrophy, and Intractable Seizures. Am J Hum Genet 2014; 94:547-58. PubMed
  • Bae BI, Tietjen I, Atabay KD, Evrony GD, Johnson MB, Asare E, Wang PP, Murayama AY, Im K, Lisgo SN, Overman L, Šestan N, Chang BS, Barkovich AJ, Grant PE, Topçu M, Politsky J, Okano H, Piao X, Walsh CA. Evolutionarily dynamic alternative splicing of GPR56 regulates regional cerebral cortical patterning. Science 2014; 343:764-8. PubMed
  • Poduri A, Evrony GD, Cai X, Walsh CA. Somatic mutation, genomic variation, and neurological disease. Science 2013; 341:1237758. PubMed
  • Yu TW, Chahrour MH, Coulter ME, Jiralerspong S, Okamura-Ikeda K, Ataman B, Schmitz-Abe K, Harmin DA, Adli M, Malik AN, D'Gama AM, Lim ET, Sanders SJ, Mochida GH, Partlow JN, Sunu CM, Felie JM, Rodriguez J, Nasir RH, Ware J, Joseph RM, Hill RS, Kwan BY, Al-Saffar M, Mukaddes NM, Hashmi A, Balkhy S, Gascon GG, Hisama FM, LeClair E, Poduri A, Oner O, Al-Saad S, Al-Awadi SA, Bastaki L, Ben-Omran T, Teebi AS, Al-Gazali L, Eapen V, Stevens CR, Rappaport L, Gabriel SB, Markianos K, State MW, Greenberg ME, Taniguchi H, Braverman NE, Morrow EM, Walsh CA. Using whole-exome sequencing to identify inherited causes of autism. Neuron 2013; 77:259-73. PubMed
  • Yang YJ, Baltus AE, Mathew RS, Murphy EA, Evrony GD, Gonzalez DM, Wang EP, Marshall-Walker CA, Barry BJ, Murn J, Tatarakis A, Mahajan MA, Samuels HH, Shi Y, Golden JA, Mahajnah M, Shenhav R, Walsh CA. Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation. Cell 2012; 151:1097-112. PubMed
  • Evrony GD, Cai X, Lee E, Hills LB, Elhosary PC, Lehmann HS, Parker JJ, Atabay KD, Gilmore EC, Poduri A, Park PJ, Walsh CA. Single-neuron sequencing analysis of l1 retrotransposition and somatic mutation in the human brain. Cell 2012; 151:483-96. PubMed
  • Mochida GH, Ganesh VS, de Michelena MI, Dias H, Atabay KD, Kathrein KL, Huang HT, Hill RS, Felie JM, Rakiec D, Gleason D, Hill AD, Malik AN, Barry BJ, Partlow JN, Tan WH, Glader LJ, Barkovich AJ, Dobyns WB, Zon LI, Walsh CA. CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development. Nat Genet 2012; 44:1260-1264. PubMed
  • Lehtinen MK, Zappaterra MW, Chen X, Yang YJ, Hill AD, Lun M, Maynard T, Gonzalez D, Kim S, Ye P, D'Ercole AJ, Wong ET, Lamantia AS, Walsh CA. The cerebrospinal fluid provides a proliferative niche for neural progenitor cells. Neuron 2011; 69:893-905. PubMed
  • Lizarraga SB, Margossian SP, Harris MH, Campagna DR, Han AP, Blevins S, Mudbhary R, Barker JE, Walsh CA, Fleming MD. Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors. Development 2010; 137:1907-17. PubMed
  • Shen J, Gilmore EC, Marshall CA, Haddadin M, Reynolds JJ, Eyaid W, Bodell A, Barry B, Gleason D, Allen K, Ganesh VS, Chang BS, Grix A, Hill RS, Topcu M, Caldecott KW, Barkovich AJ, Walsh CA. Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. Nat Genet 2010; 42:245-9. PubMed
  • Powers SE, Taniguchi K, Yen W, Melhuish TA, Shen J, Walsh CA, Sutherland AE, Wotton D. Tgif1 and Tgif2 regulate Nodal signaling and are required for gastrulation. Development 2009; 137:249-59. PubMed
  • Mochida GH, Mahajnah M, Hill AD, Basel-Vanagaite L, Gleason D, Hill RS, Bodell A, Crosier M, Straussberg R, Walsh CA. A truncating mutation of TRAPPC9 is associated with autosomal-recessive intellectual disability and postnatal microcephaly. Am J Hum Genet 2009; 85:897-902. PubMed
  • Manzini MC,Gleason D,Chang BS,Hill RS,Barry BJ,Partlow JN,Poduri A,Currier S,Galvin-Parton P,Shapiro LR,Schmidt K,Davis JG,Basel-Vanagaite L,Seidahmed MZ,Salih MA,Dobyns WB,Walsh CA. Ethnically diverse causes of Walker-Warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the Middle East. Hum Mutat 2008; 29:E231-41. PubMed
  • Pawlisz AS, Mutch C, Wynshaw-Boris A, Chenn A, Walsh CA, Feng Y. Lis1-Nde1 dependent neuronal fate control determines cerebral cortical size and lamination. Hum Mol Genet 2008; 17:2441-55. PubMed
  • Cubelos B,Sebastian-Serrano A,Kim S,Moreno-Ortiz C,Redondo JM,Walsh CA,Nieto M. Cux-2 controls the proliferation of neuronal intermediate precursors of the cortical subventricular zone. Cereb Cortex 2007; 18:1758-70. PubMed
  • Li S,Jin Z,Koirala S,Bu L,Xu L,Hynes RO,Walsh CA,Corfas G,Piao X. GPR56 regulates pial basement membrane integrity and cortical lamination. J Neurosci 2008; 28:5817-26. PubMed
  • Friocourt G, Liu JS, Antypa M, Rakic S, Walsh CA, Parnavelas JG. Both doublecortin and doublecortin-like kinase play a role in cortical interneuron migration. J Neurosci 2007; 27:3875-83. PubMed
  • Feng Y, Chen MH, Moskowitz IP, Mendonza AM, Vidali L, Nakamura F, Kwiatkowski DJ, Walsh CA. Filamin A (FLNA) is required for cell-cell contact in vascular development and cardiac morphogenesis. Proc Natl Acad Sci U S A 2006; 103:19836-41. PubMed
  • Basel-Vanagaite L, Muncher L, Straussberg R, Pasmanik-Chor M, Yahav M, Rainshtein L, Walsh CA, Magal N, Taub E, Drasinover V, Shalev H, Attia R, Rechavi G, Simon AJ, Shohat M. Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis. Ann Neurol 2006; 60:214-22. PubMed
  • Sun T, Walsh CA. Molecular approaches to brain asymmetry and handedness. Nat Rev Neurosci 2006; 7:655-62. PubMed
  • Neal J, Apse K, Sahin M, Walsh CA, Sheen VL. Deletion of chromosome 1p36 is associated with periventricular nodular heterotopia. Am J Med Genet A 2006; 140:1692-5. PubMed
  • Rajab A, Yoo SY, Abdulgalil A, Kathiri S, Ahmed R, Mochida GH, Bodell A, Barkovich AJ, Walsh CA. An autosomal recessive form of spastic cerebral palsy (CP) with microcephaly and mental retardation. Am J Med Genet A 2006; 140:1504-10. PubMed
  • Parrini E, Ramazzotti A, Dobyns WB, Mei D, Moro F, Veggiotti P, Marini C, Brilstra EH, Dalla Bernardina B, Goodwin L, Bodell A, Jones MC, Nangeroni M, Palmeri S, Said E, Sander JW, Striano P, Takahashi Y, Van Maldergem L, Leonardi G, Wright M, Walsh CA, Guerrini R. Periventricular heterotopia: phenotypic heterogeneity and correlation with Filamin A mutations. Brain 2006; 129:1892-906. PubMed
  • Sun T, Collura RV, Ruvolo M, Walsh CA. Genomic and evolutionary analyses of asymmetrically expressed genes in human fetal left and right cerebral cortex. Cereb Cortex 2006; 16 Suppl 1:i18-25. PubMed
  • Ferland RJ, Gaitanis JN, Apse K, Tantravahi U, Walsh CA, Sheen VL. Periventricular nodular heterotopia and Williams syndrome. Am J Med Genet A 2006; 140:1305-11. PubMed
  • Sheen VL, Ferland RJ, Neal J, Harney M, Hill RS, Banham A, Brown P, Chenn A, Corbo J, Hecht J, Folkerth R, Walsh CA. Neocortical neuronal arrangement in Miller Dieker syndrome. Acta Neuropathol 2006; 111:489-96. PubMed
  • Sheen VL, Ferland RJ, Harney M, Hill RS, Neal J, Banham AH, Brown P, Chenn A, Corbo J, Hecht J, Folkerth R, Walsh CA. Impaired proliferation and migration in human Miller-Dieker neural precursors. Ann Neurol 2006; 60:137-144. PubMed
  • Tsao JW, Neal J, Apse K, Stephan MJ, Dobyns WB, Hill RS, Walsh CA, Sheen VL. Cerebellar ataxia with progressive improvement. Arch Neurol 2006; 63:594-7. PubMed
  • Olson EC, Kim S, Walsh CA. Impaired neuronal positioning and dendritogenesis in the neocortex after cell-autonomous Dab1 suppression. J Neurosci 2006; 26:1767-75. PubMed
  • Chang BS, Apse KA, Caraballo R, Cross JH, Mclellan A, Jacobson RD, Valente KD, Barkovich AJ, Walsh CA. A familial syndrome of unilateral polymicrogyria affecting the right hemisphere. Neurology 2006; 66:133-5. PubMed
  • Deuel TA, Liu JS, Corbo JC, Yoo SY, Rorke-Adams LB, Walsh CA. Genetic interactions between doublecortin and doublecortin-like kinase in neuronal migration and axon outgrowth. Neuron 2006; 49:41-53. PubMed
  • Piao X, Chang BS, Bodell A, Woods K, Benzeev B, Topcu M, Guerrini R, Goldberg-Stern H, Sztriha L, Dobyns WB, Barkovich AJ, Walsh CA. Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes. Ann Neurol 2005; 58:680-7. PubMed
  • Hill RS, Walsh CA. Molecular insights into human brain evolution. Nature 2005; 437:64-7. PubMed
  • Sun T, Patoine C, Abu-Khalil A, Visvader J, Sum E, Cherry TJ, Orkin SH, Geschwind DH, Walsh CA. Early asymmetry of gene transcription in embryonic human left and right cerebral cortex. Science 2005; 308:1794-8. PubMed
  • Shen J, Walsh CA. Targeted disruption of Tgif, the mouse ortholog of a human holoprosencephaly gene, does not result in holoprosencephaly in mice. Mol Cell Biol 2005; 25:3639-47. PubMed
  • Feng Y, Walsh CA. Mitotic spindle regulation by Nde1 controls cerebral cortical size. Neuron 2004; 44:279-93. PubMed
  • Piao X, Hill RS, Bodell A, Chang BS, Basel-Vanagaite L, Straussberg R, Dobyns WB, Qasrawi B, Winter RM, Innes AM, Voit T, Ross ME, Michaud JL, D. G protein-coupled receptor-dependent development of human frontal cortex. Science 2004; 303:2033-6. PubMed
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