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

Photo of Christopher A. Walsh, MD, PhD

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


christopher.walsh@childrens.harvard.edu

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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

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 from Harvard Catalyst Profiles

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  • Ganz J, Maury EA, Becerra B, Bizzotto S, Doan RN, Kenny CJ, Shin T, Kim J, Zhou Z, Ligon KL, Lee EA, Walsh CA. Rates and patterns of clonal oncogenic mutations in the normal human brain. 2021. PubMed
  • Doan RN, Miller MB, Kim SN, Rodin RE, Ganz J, Bizzotto S, Morillo KS, Huang AY, Digumarthy R, Zemmel Z, Walsh CA. MIPP-Seq: ultra-sensitive rapid detection and validation of low-frequency mosaic mutations. BMC Med Genomics 2021; 14:47. PubMed
  • Bizzotto S, Dou Y, Ganz J, Doan RN, Kwon M, Bohrson CL, Kim SN, Bae T, Abyzov A, , Park PJ, Walsh CA. Landmarks of human embryonic development inscribed in somatic mutations. Science 2021; 371:1249-1253. PubMed
  • Dou Y, Kwon M, Rodin RE, Cortés-Ciriano I, Doan R, Luquette LJ, Galor A, Bohrson C, Walsh CA, Park PJ. Accurate detection of mosaic variants in sequencing data without matched controls. Nat Biotechnol 2020; 38:314-319. PubMed
  • Bohrson CL, Barton AR, Lodato MA, Rodin RE, Luquette LJ, Viswanadham VV, Gulhan DC, Cortés-Ciriano I, Sherman MA, Kwon M, Coulter ME, Galor A, Walsh CA, Park PJ. Linked-read analysis identifies mutations in single-cell DNA-sequencing data. Nat Genet 2019; 51:749-754. PubMed
  • Coulter ME, Dorobantu CM, Lodewijk GA, Delalande F, Cianferani S, Ganesh VS, Smith RS, Lim ET, Xu CS, Pang S, Wong ET, Lidov HGW, Calicchio ML, Yang E, Gonzalez DM, Schlaeger TM, Mochida GH, Hess H, Lee WA, Lehtinen MK, Kirchhausen T, Haussler D, Jacobs FMJ, Gaudin R, Walsh CA. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles. Cell Rep 2018; 24:973-986.e8. PubMed
  • Baizabal JM, Mistry M, García MT, Gómez N, Olukoya O, Tran D, Johnson MB, Walsh CA, Harwell CC. The Epigenetic State of PRDM16-Regulated Enhancers in Radial Glia Controls Cortical Neuron Position. Neuron 2018; 98:945-962.e8. PubMed
  • D'Gama AM, Woodworth MB, Hossain AA, Bizzotto S, Hatem NE, LaCoursiere CM, Najm I, Ying Z, Yang E, Barkovich AJ, Kwiatkowski DJ, Vinters HV, Madsen JR, Mathern GW, Blümcke I, Poduri A, Walsh CA. Somatic Mutations Activating the mTOR Pathway in Dorsal Telencephalic Progenitors Cause a Continuum of Cortical Dysplasias. Cell Rep 2017; 21:3754-3766. PubMed
  • Lodato MA, Rodin RE, Bohrson CL, Coulter ME, Barton AR, Kwon M, Sherman MA, Vitzthum CM, Luquette LJ, Yandava C, Yang P, Chittenden TW, Hatem NE, Ryu SC, Woodworth MB, Park PJ, Walsh CA. Aging and neurodegeneration are associated with increased mutations in single human neurons. Science 2017. PubMed
  • Sherman MA, Barton AR, Lodato MA, Vitzthum C, Coulter ME, Walsh CA, Park PJ. PaSD-qc: quality control for single cell whole-genome sequencing data using power spectral density estimation. Nucleic Acids Res 2017. PubMed
  • Evrony GD, Cordero DR, Shen J, Partlow JN, Yu TW, Rodin RE, Hill RS, Coulter ME, Lam AN, Jayaraman D, Gerrelli D, Diaz DG, Santos C, Morrison V, Galli A, Tschulena U, Wiemann S, Martel MJ, Spooner B, Ryu SC, Elhosary PC, Richardson JM, Tierney D, Robinson CA, Chibbar R, Diudea D, Folkerth R, Wiebe S, Barkovich AJ, Mochida GH, Irvine J, Lemire EG, Blakley P, Walsh CA. Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome. Genome Res 2017. PubMed
  • Jamuar SS, Schmitz-Abe K, D'Gama AM, Drottar M, Chan WM, Peeva M, Servattalab S, Lam AN, Delgado MR, Clegg NJ, Zayed ZA, Dogar MA, Alorainy IA, Jamea AA, Abu-Amero K, Griebel M, Ward W, Lein ES, Markianos K, Barkovich AJ, Robson CD, Grant PE, Bosley TM, Engle EC, Walsh CA, Yu TW. Biallelic mutations in human DCC cause developmental split-brain syndrome. Nat Genet 2017; 49:606-612. PubMed
  • Woodworth MB, Girskis KM, Walsh CA. Building a lineage from single cells: genetic techniques for cell lineage tracking. Nat Rev Genet 2017. PubMed
  • Jayaraman D, Kodani A, Gonzalez DM, Mancias JD, Mochida GH, Vagnoni C, Johnson J, Krogan N, Harper JW, Reiter JF, Yu TW, Bae BI, Walsh CA. Microcephaly Proteins Wdr62 and Aspm Define a Mother Centriole Complex Regulating Centriole Biogenesis, Apical Complex, and Cell Fate. Neuron 2016; 92:813-828. PubMed
  • Zhang X, Chen MH, Wu X, Kodani A, Fan J, Doan R, Ozawa M, Ma J, Yoshida N, Reiter JF, Black DL, Kharchenko PV, Sharp PA, Walsh CA. Cell-Type-Specific Alternative Splicing Governs Cell Fate in the Developing Cerebral Cortex. Cell 2016; 166:1147-1162.e15. PubMed
  • Evrony GD, Lee E, Park PJ, Walsh CA. Resolving rates of mutation in the brain using single-neuron genomics. Elife 2016. PubMed
  • D'Gama AM, Pochareddy S, Li M, Jamuar SS, Reiff RE, Lam AT, Sestan N, Walsh CA. Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms. Neuron 2015; 88:910-7. PubMed
  • Lodato MA, Woodworth MB, Lee S, Evrony GD, Mehta BK, Karger A, Lee S, Chittenden TW, D'Gama AM, Cai X, Luquette LJ, Lee E, Park PJ, Walsh CA. Somatic mutation in single human neurons tracks developmental and transcriptional history. Science 2015; 350:94-8. PubMed
  • Jamuar SS, Walsh CA. Genomic Variants and Variations in Malformations of Cortical Development. Pediatr. Clin. North Am. 2015; 62:571-585. 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
  • 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
  • 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
  • Hu WF, Pomp O, Ben-Omran T, Kodani A, Henke K, Mochida GH, Yu TW, Woodworth MB, Bonnard C, Raj GS, Tan TT, Hamamy H, Masri A, Shboul M, Al Saffar M, Partlow JN, Al-Dosari M, Alazami A, Alowain M, Alkuraya FS, Reiter JF, Harris MP, Reversade B, Walsh CA. Katanin p80 regulates human cortical development by limiting centriole and cilia number. Neuron 2014; 84:1240-57. 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
  • Jamuar SS, Lam AT, Kircher M, D'Gama AM, Wang J, Barry BJ, Zhang X, Hill RS, Partlow JN, Rozzo A, Servattalab S, Mehta BK, Topcu M, Amrom D, Andermann E, Dan B, Parrini E, Guerrini R, Scheffer IE, Berkovic SF, Leventer RJ, Shen Y, Wu BL, Barkovich AJ, Sahin M, Chang BS, Bamshad M, Nickerson DA, Shendure J, Poduri A, Yu TW, Walsh CA. Somatic mutations in cerebral cortical malformations. N Engl J Med 2014; 371:733-43. PubMed
  • Manzini MC, Xiong L, Shaheen R, Tambunan DE, Di Costanzo S, Mitisalis V, Tischfield DJ, Cinquino A, Ghaziuddin M, Christian M, Jiang Q, Laurent S, Nanjiani ZA, Rasheed S, Hill RS, Lizarraga SB, Gleason D, Sabbagh D, Salih MA, Alkuraya FS, Walsh CA. CC2D1A regulates human intellectual and social function as well as NF-κB signaling homeostasis. Cell Rep 2014; 8:647-55. 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
  • 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; 44:1260-4. 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
  • 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 2010; 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
  • 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 2008; 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
  • 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
  • Sun T, Walsh CA. Molecular approaches to brain asymmetry and handedness. Nat Rev Neurosci 2006; 7:655-62. 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, 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
  • 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, 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, Déscarie JC, Barkovich AJ, Walsh CA. G protein-coupled receptor-dependent development of human frontal cortex. Science 2004; 303:2033-6. PubMed
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HCC members that share similar concepts* with Christopher A. Walsh, MD, PhD but have yet to coauthor a publication with this researcher.

* Concepts are MeSH terms, automatically derived from member publications

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