Janine LaSalle, Ph.D.

 Janine  LaSalle, Ph.D.

Position

  • Professor
  • Medical Microbiology and Immunology (M.I.N.D. Institute, Genome Center)

Epigenetics of Human Neurodevelopmental Disorders

Research Summary

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.

Teaching Interests:

Teaching Interests: Genetics, immunology

Courses Taught:

GGG 201a Genetic Analyses - Term(s): Fall

MMI 480A Medical Immunology - Term(s): Spring

OBG 420 Genetics and Reproduction - Term(s): Spring

Select Publications

Samaco RC, Hogart A, and LaSalle JM. 2005. Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Hum. Mol. Genet. 14:483-492.

Thatcher KN, Peddada S, Yasui DH, and LaSalle JM. 2005. Homologous pairing of 15q11-13 imprinted domains in brain is developmentally regulated but deficient in Rett and autism samples. Hum. Mol. Genet. 14:785-797.

LaSalle JM, Hogart A, Thatcher KN. 2005. Rett Syndrome: A Rosetta Stone for Understanding the Molecular Pathogenesis of Autism, in International Review of Neurobiology, D. Dhossche, ed. Elsevier Publishers. 71:131-165.

Thatcher KN and LaSalle JM. 2006. Dynamic changes in Histone H3 lysine 9 acetylation localization patterns during neuronal maturation require MeCP2. Epigenetics. 1:24-31. (inaugural issue, cover article)

Peddada S, Yasui DH, and LaSalle JM. 2006. Inhibitors of differentiation (ID1, ID2, ID3, ID4) genes are neuronal targets of MeCP2 that are elevated in Rett syndrome. Hum. Mol. Genet. 15:2003-2014. (cover article)

Nagarajan RP, Hogart A, Gwye Y, Martin M, and LaSalle JM. 2006. Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation Epigenetics, 4:172-182.

LaSalle JM. 2006. The Odyssey of MeCP2 and Parental Imprinting. Epigenetics. 2:5-10.

Hogart A, Nagarajan RP, Yasui DH, Patzel KA, and LaSalle JM. 2007. 15q11-13 GABAA receptor genes are biallelically expressed in brain yet are epigenetically dysregulated in autism-spectrum disorders. Hum. Mol. Genet. 16:691-703.

Yasui DH, Peddada S, Bieda MC, Vallero RO, Hogart A, Nagarajan RP, Thatcher KN, Farnham PJ, LaSalle JM. 2007. Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes. Proc. Natl. Acad. Sci. 104:19416-19421.

Nagarajan RP, Patzel KA, Martin M, Yasui DH, Swanberg SE, Hertz-Picciotto I, Hansen RL, Van de Water J, Pessah IN, Jiang R, Robinson WP, LaSalle JM. 2008. MECP2 promoter methylation and X chromosome inactivation in autism. Autism Res. 1:169-178.

Hogart A, Patzel KA, and LaSalle JM. 2008. Gender influences monoallelic expression of ATP10A in human brain. Hum. Genet. 124:235-242.

Hogart A, Leung KN, Wang NJ, Wu DJ, Driscoll J, Vallero RO, Schanen NC, LaSalle JM. 2008. Chromosome 15q11-13 duplication syndrome brain reveals epigenetic alterations in gene expression not predicted from copy number. J. Med. Genet., in press

Adegbola AA, Gonzales ML, Chess A, LaSalle JM, Cox GF. An unusually mild neurobehavioral phenotype associated with a novel p.P152A MECP2 mutation that reduces protein-heterochromatin binding. Hum Genet. In press

Swanberg SE, Nagarajan RP, Peddada S, Yasui DH, LaSalle JM. Reciprocal co-regulation of EGR2 and MECP2 is disrupted in Rett syndrome and autism. Hum. Mol Genet. In press

Affiliations

M.I.N.D. Institute

Cancer Center

Rowe Program in Human Genetics

Genome Center

Biochemistry and Molecular Biology

Biophysics

Genetics

Neuroscience