Offices and Labs
Profile IntroductionMy laboratory is interested in the role epigenetics in human autism-spectrum disorders. Epigenetics is the study of heritable changes in chromosomes that are not encoded in the DNA sequence, including DNA methylation and chromatin organization. The clinical applications of our research include understanding the pathogenesis of the neurodevelopmental disorders autism, Rett syndrome, Prader-Willi syndrome, Dup15q, and Angelman syndrome. We are currently using mouse models to investigate the epigenetic pathways in Rett and Prder-Willi syndrome. We also utilize human postmortem brain and placenta samples from individuals with autism spectrum disorders to investigate the epigenetic mark of DNA methylation genome-wide using high-throughput sequencing and bioinformatic approaches. We have several projects designed to look at DNA methylation at the interface of genetic and environmental interactions in idiopathic autism spectrum disorders.
Epigenetics of autism-spectrum disorders
Our laboratory is interested in the role of epigenetics in human autism-spectrum disorders. Epigenetics is the study of heritable changes in chromosomes that are not encoded in the DNA sequence, including DNA methylation and chromatin organization. The clinical applications of our research include understanding the pathogenesis of the neurodevelopmental disorders autism, Rett syndrome, Prader-Willi syndrome, Dup15q syndrome, and Angelman syndrome. We take a “Rosetta’s stone” approach to decoding the elusive etiology of autism by looking for clues in the epigenetic pathways disrupted in rare genetic disorders on the autism spectrum. Our laboratory also investigates how early life exposures and experiences impact the DNA methylome using genom-wide approaches. In addition, we are interested in the functions of noncoding RNA at the heart of the Prader-Willi locus that are expressed in postnatal neurons and regulate circadian genes and diurnal cycles of cellular metabolism. We also are investigating the impact common organic pollutants on DNA methylation and chromatin organization in 15q11-13 duplication syndrome. We have several ongoing collaborations that seek to integrate genetics with fields of Neuroscience, Nutrition, Toxicology, and Epidemiology.
Department and Center Affiliations
CBS Grad Group Affiliations
Specialties / Focus
- Chromosome Biology
- Human Genetics and Genomics
- Computational Biology
- Animal Genomics
- Integrated Genetics and Genomics
- Molecular Medicine
- Chromosome Dynamics and Nuclear Function
- Molecular Genetics
- Gene Regulation
- Genomics, Proteomics and Metabolomics
Dag Yasui, Ph.D., Project Scientist; Annie Vogel Ciernia, Ph.D., Postdoctoral Fellow; Rochelle Coulson, Graduate student, Genetics; Yihui Zhu, Graduate student, IGG; Charles Mourdant, Graduate student, BMCDB; Jesse Lopez, Graduate student, IGG; Theresa Totah, Junior Specialist; Tianna Grant, Junior Specialist, PREP scholar
Crary-Dooley FK, Tam ME, Dunaway KW, Hertz-Picciotto I, Schmidt RJ, LaSalle JM. 2017. A comparison of existing global DNA methylation assays to low-coverage whole genome bisulfite sequencing for epidemiology studies. Epigenetics. Jan 5:0. doi: 10.1080/15592294.2016.1276680. [Epub ahead of print] PMID:28055307
Dunaway KW, Gorrha S, Malelski L, Urraca N, Lein PJ, Korf I, Reiter LT, LaSalle JM. 2016. Dental pulp stem cells model early life and imprinted DNA methylation patterns. Stem Cells. doi: 10.1002/stem.2563. [Epub ahead of print] PMID:28032673
Schroeder DI, Schmidt RJ, Crary FK, Walker CK, Ozonoff S, Tancredi DJ, Hertz-Picciotto I, LaSalle JM. Placental methylome analysis from a prospective autism study. Mol Autism, 7:51 PMID: 28018572
Schmidt RJ, Schroeder DI, Crary FK, Barkoski JM, Tancredi DJ, Walker CK, Ozonoff S, Hertz-Picciotto I, LaSalle JM. 2016. Self-reported pregnancy exposures and placental DNA methylation in the MARBLES prospective autism sibling study. Environmental Epigenetics, doi: 10.1093/eep/dvw024
Medici V, Kieffer DA, Shibata NM, Chima H, Kim K, Canovas A, Medrano JF, Islas-Trejo AD, Kharbanda KK, Olson K, Su RJ, Islam MS, Syed R, Keen CL, Miller AY, Rutledge JC, Halsted CH, LaSalle JM. 2016. Wilson Disease: epigenetic effects of choline supplementation on phenotype and clinical course in a mouse model. 64. Epigenetics. 11(11):804-818. PMID: 27611852
Veeraragavan S, Wan Y-W, Connolly DR, Hamilton SM, Ward CS, Soriano S, Pitcher MR, McGraw CM, Huang SG, Green JR, Yuva LA, Liang AJ, Neul JL, Yasui DH, LaSalle JM, Liu Z, Paylor R, Samaco RC. 2016. Loss of MeCP2 in the rat models regression, impaired sociability and transcriptional deficits of Rett syndrome. Hum Mol Genet. 25:3284-3302. PMID:27365498
Dunaway KW, Islam MS, Coulson RL, Lopez SJ, Vogel Ciernia A, Chu RG, Yasui DH, Pessah IN, Lott P, Mordaunt C, Meguro-Horike M, Horike S, Korf I, LaSalle JM. 2016. Cumulative impact of polychlorinated biphenyl and large chromosomal duplications on DNA methylation, chromatin, and expression of autism genes. Cell Reports. 17:3035-3048. PMID: 27974215
Rube HT, Lee W, Hejna M, Chen H, Yasui DH, LaSalle JM, Song JS, Gong Q. 2016. Sequence features accurately predict genome-wide MeCP2 binding in vivo. Nature Communications, 7:11025. PMID: 27008915
Vogel Ciernia A, LaSalle JM. 2016. The landscape of DNA methylation amidst a perfect storm of autism etiologies. Nature Reviews Neuroscience, 17:411-23.
Crawley JN, Heyer WD, LaSalle JM. 2016. Autism and cancer share risk genes, pathways and drug targets. Trends in Genetics. 32:139-146. 32:139-46.
LaSalle JM, Reiter LT, Chamberlain SJ. 2015. Epigenetic regulation of UBE3A and roles in human neurodevelopmental disorders. Epigenomics, 7:1213-28.
Powell WT and LaSalle JM. 2015. Epigenetic mechanisms in diurnal cycles of metabolism and neurodevelopment. Hum. Mol. Genet. pii: ddv234. Epub 2015 Jun 23.
Schroeder DI, Jayashankar K, Douglas KC, Thirkill TL, York D, Dickinson PJ, Williams LE, Samollow PB, Ross PJ, Bannasch DL, Douglas GC, LaSalle JM. 2015. Early developmental and evolutionary origins of gene body DNA methylation patterns in mammalian placentas. PLOS Genet. Aug 4;11(8):e1005442
Lee W, Yun J-M, Woods R, Dunaway K, Yasui DH, LaSalle JM, Gong Q. 2014. MeCP2 Regulates Activity-dependent Transcriptional Responses and Olfactory Circuitry Refinement. Hum. Mol. Genet., 23:6366-6374.
Yasui DH, Gonzales ML, Aflatooni JO, Crary FK, Hu DJ, Gavino BJ, Golub MS, Vincent JB, Carolyn Schanen N, Olson CO, Rastegar M, Lasalle JM. 2014. Mice with an isoform-ablating Mecp2 exon 1 mutation recapitulate the neurologic deficits of Rett syndrome. Hum Mol Genet. 23:2447-2458
Schroeder DI, Blair J, Lott P, Yu HO, Hing, D, Crary F, Ashwood P, Walker C, Korf I, Robinson WP, and LaSalle JM. 2013. The human placental methylome. Proc. Natl. Acad. Sci., 110:6037-6042.
Yasui DH, Xu H, Dunaway KW, LaSalle JM, Jin LW, and Maezawa I. 2013. MeCP2 modulates gene expression pathways in astrocytes. Molecular Autism. 4:3.
LaSalle JM. 2013. Epigenomic strategies at the interface of genetic and environmental risk factors for autism. J Hum Genet. 58:396-401
LaSalle JM, Powell WT, and Yasui DH. Epigenetic Layers and Players Underlying Neurodevelopment. Trends in Neurosciences. 36:460-470
Powell WT, Coulson RL, Crary FK, Gonzales ML, Adams S, Ach RA, Tsang P, Yamada NA, Yasui DH, Chedin F, and LaSalle JM. Topotecan stabilizes R-loops to inhibit transcription in the Prader-Willi/Angelman imprinted locus. Proc. Natl. Acad. Sci. 110:13938-13943.
LaSalle JM. 2013. Autism genes keep turning up chromatin. OA Autism. 19:15.
Medici V, Shibata NM, Kharbanda KK, Islam MS, Keen CL, Kim K, Tillman B, French SW, Halsted CH, Lasalle JM. 2013. Maternal choline modifies fetal liver copper, gene expression, DNA methylation, and neonatal growth in the tx-j mouse model of Wilson disease. Epigenetics. Nov 12;9(2). [Epub ahead of print]
Powell WT, Coulson RL, Crary FK, Wong SG, Ach RA, Tsang P, Yamada NA, Yasui DH, and LaSalle JM. 2013. A Prader-Willi locus lncRNA cloud modulates diurnal genes and energy expenditure. Hum. Mol Genet. 22:4318-4328.
Schroeder DI, LaSalle JM. 2013. How has the study of the human placenta aided our understanding of partially methylated genes? Epigenomics. 2013 Dec;5(6):645-54.