Department of Medical Microbiology and Immunology, School of Medicine
Perinatal Origins of Disparities Center
Environmental Health Sciences Center
My 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, as well as placenta and cord blood 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 genome-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, Health Disparities, and Epidemiology.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
- Integrative Genetics and Genomics
Specialties / Focus
- Animal Genomics
- Chromosome Biology
- Chromosome Dynamics and Nuclear Function
- Computational Biology
- Gene Regulation
- Genomics, Proteomics and Metabolomics
- Human Genetics and Genomics
- Integrated Genetics and Genomics
- Molecular Genetics
- Molecular Medicine
- Spectroscopy and Imaging
- Health Disparities
- GGG 290A Student Presentation Seminar, Fall (even years)
- PHA 250 Functional Genomics: from Bench to Bedside, Spring (even years)
- GGG 201A Advanced Genetic Analyses, Fall
- LaSalle Lab http://lasallelab.ucdavis.edu/
- Dag Yasui, Ph.D., Project Scientist; Ben Laufer, Ph.D., Postdoctoral Fellow; Kari Neier, Ph.D., Postdoctoral Fellow; Charles Mordaunt, Ph.D., Postdoctoral Fellow; Yihui Zhu, Graduate student, IGG; Oran Gutierrez, Graduate student, IGG; Osman Sharifi, Graduate student, BMCDB; Aron Judd Mendiola, Graduate student, BMCDB; Julia Jianu, Junior Specialist; Hyeyeon Hwang, Junior Specialist
- Editorial board, Human Molecular Genetics
- Editorial Board, Molecular Autism
- Brandewein Award in Genetic Research
- Editorial Board, Environmental Epigenetics
- Top Peer reviewer in Molecular Biology and Genetics, Publons
- American Society of Human Genetics
- International Society for Autism Research
- Society for Neuroscience
- 1993 PhD Immunology Harvard University
Mordaunt CE, Kieffer DA, Shibata N, Czlonkowska A, Litwin T, Weiss KH, Bowlus CL, Sarkar S, Cooper S, Wan Y-JY, Ali M, LaSalle JM*, Medici V*. 2019. The epigenomic signature of Wilson Disease. Epigenetics and Chromatin. 12:10.
Vogel Ciernia A, Laufer BI, Hwang H, Dunaway KD, Mordaunt CE, Coulson RL, Yasui DH, LaSalle JM. 2019. Epigenomic convergence of neural-immune risk factors in neurodevelopmental disorder cortex. Cerebral Cortex, in press
Laufer BI, Hwang H, Vogel Ciernia A, Mordaunt CE, LaSalle JM. 2019. Whole genome bisulfite sequencing of Down syndrome brain reveals regional DNA hypermethylation and novel disease insights. Epigenetics, 14: 677-684.
Zhu Y, Mordaunt CE, Yasui DH, Marathe R, Coulson R, Dunaway K, Walker C, Ozonoff S, Hertz-Picciotto I, Schmidt RJ, LaSalle JM. 2019. Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study. Hum. Mol. Genet., 28: 2659-2674.
Mordaunt CE, Park BY, Bakulski KM, Feinberg JI, Croen LA, Ladd-Acosta C, Newschaffer CJ, Volk HE, Ozonoff S, Hertz-Picciotto I, LaSalle JM*, Schmidt RJ*, Fallin D*. 2019. A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood. Mol. Autism, 10:36
Lopez SJ, Segal DJ, LaSalle JM. 2019. UBE3A: a ubiquitin ligase with genome-wide impact in neurodevelopmental disorders. Frontiers in Molecular Neuroscience. 11:476.
Mordaunt CE, Shibata N, Kieffer DA, Czlonkowska A, Litwin T, Weiss KH, Gotthardt DN, Olson K, Wei D, Cooper S, Wan Y-JY, Ali M, LaSalle JM*, Medici V*. 2018. Epigenetic changes of the thioredoxin system in the tx-j mouse model and in patients with Wilson disease. Hum. Mol. Genet., 27:3854-3869.
Coulson RL and LaSalle JM. 2018. Epigenetics of circadian rhythms in imprinted neurodevelopmental disorders. Prog Mol Biol Transl Sci. 157:67-92.
Vogel Ciernia A, Yasui DH, Pride MC, Durbin-Johnson B, Noronha A, Chang A, Ramsey JJ, Knotts T, Rutkowsky J, Crawley JN, LaSalle JM. 2018. MeCP2 isoform e1 mutant mice recapitulate motor and metabolic phenotypes of Rett syndrome. Hum. Mol. Genet., 27:4077-4093.
Coulson RL, Powell WT, Yasui DH, Dileep G, Resnick J, LaSalle JM. 2018. Prader-Willi locus Snord116 RNA processing requires an active endogenous allele and neuron-specific splicing by Rbfox3/NeuN. Hum. Mol. Genet., 27:4051-4060.
Coulson RL, Yasui DH, Dunaway K, Laufer BI, Vogel Ciernia A, Zhu Y, Mordaunt CE, Totah TS, LaSalle JM. 2018. Snord116-dependent diurnal rhythm of DNA methylation in mouse cortex. Nature Comm. 9:1616. PMID:29691382
Vogel Ciernia A, Laufer BI, Dunaway KW, Mordaunt CE, Coulson RL, Totah TS, Stolzenberg DS, Frahm JC, Singh-Taylor A, Baram TZ, LaSalle J, Yasui, DH. 2018. Experience-dependent neuroplasticity of the developing hypothalamus: integrative epigenomic approaches. Epigenetics, 13:318-330.
Vogel Ciernia A, Careaga M, Ashwood P*, LaSalle JM*. 2018. Microglia from offspring of dams with allergic asthma exhibit epigenomic alterations in genes dysregulated in autism. GLIA. 66:505-521. PMID:29134693
Lopez SJ, Dunaway K, Islam MS, Mordaunt C, Vogel Ciernia A, Meguro-Horike M, Horike SI, Segal DJ, and LaSalle JM. UBE3A-mediated regulation of imprinted genes and epigenome-wide marks in human neurons. Epigenetics. 2(11):982-990 . PMID:28925810
Vogel Ciernia A, Pride M, Durbin-Johnson B, Noronha A, Chang A, Yasui DH, Crawley JN, and LaSalle JM. 2017. Early motor phenotype detection in a female mouse model of Rett syndrome is improved by cross-fostering. Hum. Mol. Genet. 26(10):1839-1854. PMID:28334953
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.