Janine LaSalle

image of Janine LaSalle

Professor

Departments

Genome Center
M.I.N.D. Institute
Microbiology - Medicine

Offices and Labs

3428 Tupper Hall
754-7598

Profile Introduction

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, and Angelman syndrome. Our laboratory has recently focused on a protein that binds to methylated DNA, methyl CpG binding protein 2 (MeCP2). The gene for MECP2 is on the X chromosome and is mutated in Rett syndrome and other neurodevelopmental disorders. We are currently testing the role of MeCP2 in the regulation of gene expression and the organization of parentally imprinted chromosomes. We are also investigating the role of MeCP2 in chromatin dynamics of neuronal ontogeny during post-natal neuronal maturation in the cerebral cortex.

Degrees

1993 PhD Immunology Harvard University

Research Contribution

understanding the interplay of genetics, environmental factors, and epigenetics on human neurodevelopment and human health

Research Interests

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 focuses on understanding the neuronal methylome and a protein that binds to methylated DNA, methyl CpG binding protein 2 (MeCP2). The gene for MECP2 is on the X chromosome and is mutated in Rett syndrome and other neurodevelopmental disorders. 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. 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.

Awards

Editorial board, Human Molecular Genetics
Editorial Board, Molecular Autism
Brandewein Award in Genetic Research

Department and Center Affiliations

UC Davis Cancer Center
UC Davis M.I.N.D. Institute
Rowe Program in Human Genetics
Genome Center

ProfessionalSocieties

American Society of Human Genetics
International Society for Autism Research
Society for Neuroscience

CBS Grad Group Affiliations

Neuroscience
Biophysics
Integrated Genetics and Genomics (Chair)
Biochemistry, Molecular, Cellular and Developmental Biology

Specialties / Focus

Neuroscience
  • Cellular and Molecular Neurobiology
  • Development and Plasticity
  • Medical Neuroscience
Integrated Genetics and Genomics
  • Chromosome Biology
  • Human Genetics
Biochemistry, Molecular, Cellular and Developmental Biology
  • Molecular Medicine
  • Chromosome Dynamics and Nuclear Function
  • Development

Publications

2/14/2014 12:37:59 PM
  • Mitchell MM, Lleo A, Zammataro, L, Mayo MJ, Invernizzi P, Bach N, Shimoda S, Gordon S, Podda M, Gershwin ME, Selmi C, LaSalle JM. 2011. Epigenetic investigation of variably X chromosome inactivated genes in monozygotic female twins discordant for primary biliary cirrhosis. Epigenetics. Jan 25;6(1).
  • Leung KN, Chamberlain SJ, Lalande M, and LaSalle JM. 2011. Neuronal chromatin dynamics of imprinting in development and disease. Journal of Cellular Biochemistry, 112:365-373.
  • Singleton MK, Gonzales ML, Leung, KN, Yasui DH, Schroeder DI, Dunaway K, LaSalle JM. 2011. MeCP2 is required for global heterochromatic and nucleolar changes during activity-dependent neuronal maturation. Neurobiology of Disease, 43(1):190-200.
  • Schroeder DI, Lott P, Korf I, and LaSalle JM. 2011. Large-scale methylation domains mark a functional subset of neuronally expressed genes. Genome Res. (10):1583-91.
  • Meguro-Horike M, Yasui DH, Powell W, Schroeder DI, Oshimura M, LaSalle JM, and Horike S. 2011 15q11-q13 homologous pairing and transcription are impaired in a novel neuronal model of 15q duplication syndrome. Hum Mol Genet, (19):3798-810.
  • Yasui DH, Scoles HA, Horike S, Meguro-Horike M, Dunaway KW, Schroeder DI, LaSalle JM. 2011. 15q11.2-q13.3 chromatin analysis reveals epigenetic regulation of CHRNA7 with deficiencies in Rett and autism brain. Hum. Mol Genet. (20):4311-23.
  • LaSalle JM. 2011. A genomic point-of-view on environmental factors influencing the human brain methylome. Epigenetics, (7):862-9.
  • Scoles HA, Urraca N, Chadwick SW, Reiter LT, LaSalle JM. 2011. Increased copy number for methylated maternal 15q duplications leads to changes in gene and protein expression in human cortical samples. Mol. Autism, 2(1):19.
  • Martins-Taylor K, Schroeder DI, LaSalle JM, Lalande M, Xu R-H. 2012. Role of DNMT3B in the regulation of early neural and neural crest specifiers. Epigenetics. 7:71-82.
  • Woods R, Vallero RO, Golub M, Suarez JK, Ta TA, Yasui DH, Chi L-H, Kostyniak PJ, Pessah, IN, Berman RF, LaSalle JM. 2012. Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation. Hum. Mol Genet, 21:2399-2411.
  • Gonzales ML, Adams S, Dunaway KW, LaSalle JM. 2012. Phosphorylation of distinct sites in MeCP2 modifies cofactor associations and the dynamics of transcriptional regulation. Mol Cell Biol, 32:2894-2903.
  • Mitchell MM, Woods R, Chi L-H, Schmidt RJ, Pessah IN, Kostyniak PJ, LaSalle JM. 2012. Levels of select PCB and PBDE congeners in human post-mortem brain reveal possible environmental epigenetic involvement in 15q11-q13 duplication autism spectrum disorder. Environ. Mol. Mutagenesis, 53:589-598.
  • 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
  • Medici V, Shibata NM, Kharbanda KK, Lasalle JM, Woods R, Liu S, Engelberg JA, Devaraj S, Török NJ, Jiang JX, Havel PJ, Lönnerdal B, Kim K, Halsted CH. 2012. Wilson disease: Changes in methionine metabolism and inflammation affect global DNA methylation in early liver disease. Hepatology, Sep 4. doi: 10.1002/hep.26047. [Epub ahead of print]
  • 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.
  • 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. 2014 Jan 9. [Epub ahead of print]
  • 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.

Labs

LaSalle Lab website
  • Dag Yasui, Ph.D., Project Scientist Diane Schroeder, Ph.D., Postdoctoral Fellow Saharul Islam, Ph.D., Postoctoral Fellow, Autism Research Training Program Rochelle Coulson, Graduate student, Genetics Keith Dunaway, Graduate student, Genetics Florence Crary, Junior specialist Justin Aflatooni, Junior Specialist

Teaching Interests

Genetics
website

Courses

GGG 290A Student Presentation Seminar (Fall 2012)
PHA 250 Functional Genomics: from Bench to Bedside (Spring 2012)