Janine M. Lasalle, Ph.D. Dr. Lasalle Is a Professor of Microbiology And

Janine M. LaSalle, Ph.D.

Janine M. LaSalle, Ph.D., Professor, Department of Medical Microbiology and Immunology and Rowe Program in Human Genetics, School of Medicine

Education B.S., Biology, Randolph-Macon College, 1988 Ph.D., Immunology, Harvard University, 1993

Biography Dr. LaSalle is a Professor of Microbiology and Immunology at the University of California, Davis, with memberships in the Genome Center, Rowe Program in Human Genetics, and the MIND Institute. Dr. LaSalle serves on the editorial board of the journal Human Molecular Genetics and Molecular Autism, scientific advisory boards of the International Rett Syndrome Foundation and Dup15q Alliance Foundation. The research focus in Dr. LaSalle’s laboratory is on epigenetics of neurodevelopmental disorders, including autism, Rett syndrome, Prader-Willi syndrome, Angelman syndrome, and 15q duplication syndrome. Dr. LaSalle’s laboratory has developed multiple innovative approaches for epigenetic investigations using genetic mouse models, neuronal cultures, and postmortem human brain. Dr. LaSalle’s laboratory has been successful in the use of genomic and epigenomic technologies to investigate the role of MeCP2 in the pathogenesis of Rett syndrome and autism spectrum disorders. Dr. LaSalle is the chair of the Genetics Graduate Group, and a member of three other graduate groups, including Biochemistry, Molecular, and Celluar Developmental Biology, Neuroscience, and Biophysics Her graduate students and postdoctoral fellows have received several prestigious awards from the National Science Foundation, National Institutes of Health, and Autism Speaks. Dr. LaSalle’s laboratory has been continuously funded by the NIH since 1999 and is currently funded by NICHD, NINDS, NIEHS, and the Prader-Willi Foundation.

Publications 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. MECP2 promoter methylation and X chromosome inactivation in autism. Autism Res 1:169-178, 2008.

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

Hogart A, Leung KN, Wang NJ, Wu DJ, Driscoll J, Vallero RO, Schanen NC, LaSalle JM. Chromosome 15q11-13 duplication syndrome brain reveals epigenetic alterations in gene expression not predicted from copy number. J Med Genet 46:86-93, 2009.

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 124:615-623, 2009.

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 18:525-34, 2009.

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Maezawa I, Swanberg S, Harvey D, LaSalle JM, and Jin LW. Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J. Neurosci. 29:5051-5061, 2009.

LaSalle JM and Yasui DH. 2009. The evolving role of MeCP2 in Rett syndrome and autism. Epigenomics, 1:119-130.

Leung KN, Vallero RO, DuBose AJ, Resnick JL, LaSalle JM. 2009. Imprinting regulates snoRNA-encoding chromatin and neuronal nucleolar size. Hum. Mol Genet. 18:4227-4238.

Gonzales ML and LaSalle JM. 2010. The Role of MeCP2 in Brain Development and Neurodevelopmental Disorders. Current Psychiatry Reports, 12:127-134.

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.

Artuso R, Papa FT, Filomena P, Grillo E, Mucciolo M, Yasui DH, Dunaway KW, Di Sciglio V, Mencarelli MA, Pollazzon M, Zappella M, Hayek G, Mari F, Renieri A, LaSalle JM, Ariani F. 2011. Investigation of modifier genes within copy number variations in Rett syndrome. J. Hum. Genet., 56(7):508-15.

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.

LaSalle JM. 2011. A genomic point-of-view on environmental factors influencing the human brain methylome. Epigenetics, (7):862-9.

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.

Scoles HA, Urraca N, Chadwick SW, Reiter LT, LaSalle JM. 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. 7:1. ______The MIND Institute______

Woods R, Vallero RO, Golub M, Suarez JK, Ta TA, Yasui DH, Chi L-H, Kostyniak PJ, Pessah, IN, Berman RF, LaSalle JM. Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation. Hum. Mol Genet, in press.

Presentations Epigenetics of Autism: The Interface Between Genetic and Environmental Risks, American Association for the Advancement of Science (AAAS) Meeting, Vancouver, B.C., February 16-20, 2012

Epigenetics at the interface of genetic and environmental risk factors for autism spectrum disorders. Autism Speaks Meeting on Environmental Epigenetics of Autism Spectrum Disorders, Washington D.C., December 8, 2011. The Evolving Role of MeCP2 in Neurodevelopmental Disorders, NIDA Mini-Symposium on Biological Mechanisms of Addition, Washington D.C., November 11, 2011. University of Connecticut Health Sciences Center, Brandwein Award Lecture, Hartford, CT, June 1, 2011 “Epigenetics in Autism-spectrum Disorders” Neuroepigenomics: a Tribute to Dr. Erminio Costa, University of Chicago, Chicago, IL, May 5- 6, 2011 “Chromatin Dynamics of Proximal 15q in Autism-spectrum Disorders.” Autism and Epigenetics: What’s the connection? Nemours duPont Hospital for Children, Translational Science Seminar Series, Wilmington, DE, April, 2011. Keystone Symposium on Environmental Epigenomics and Disease Susceptibility, Asheville, NC, March 2011 “Epigenetics at the interface of genetic and environmental risk factors for autism spectrum disorders” Society of Toxicology National Meeting, Washington D.C., Symposium on “Autism: Genetic, Epigenetic, and Environmental Factors Influencing Neuronal Networks,” Washington, DC, March 2011, “Long-lasting behavioral interaction between perinatal PBDE exposure and Mecp2308 mutation” George Washington University, Washington D.C., March 2011, “Epigenetics at the interface of genetic and environmental risk factors for autism spectrum disorders” Waisman Center Research Colloquium, University of Wisconson, Madison, WI. October 7, 2010. “Epigenetics at the interface of genetic and environmental risk factors for autism spectrum disorders”

Quantitative Imaging Cytometry Symposium, Boston MA, “The iCys Imaging Cytometer in the epigenetic toolbox for autism research.” August 7-8, 2010. Genetic and Environmental Toxicology Association of Northern California, Summer Symposium on Epigenomics and Human Health, Oakland, CA, “The Epigenetic Interface of Genetic and Environmental Risk Factors in Autism-spectrum Disorders.” July 20, 2010. Medical Microbiology and Immunology Seminar Series, Emerging Challenges. Davis, CA, “Autism and Epigenetics: What’s the Connection?” April 30, 2010. NIH Symposium on Chromatin Dynamics in Development and Disease, Bethesda, M.D., “Chromatin Dynamics of 15q11-14 in Autism-Spectrum Disorders.” April 7-9, 2010.

______The MIND Institute______

3 International Conference on the Social Brain: Autism and Neuroethics, Kanazawa University 150th Aniversary Symposium on March 24-25, 2010, Kanazawa, Japan. “Autism Epigenetics” Children’s Hospital of Philadelphia, Center for Autism Research, Distinguished Lecture Series, “Chromatin Dynamics of 15q11-14 in Autism-Spectrum Disorders” March 4, 2010. American Society of Nephrology conference on Epigenetics: Regulating the Genome in Development and Disease, October 2009, San Diego, CA, “Epigenetics and Autism” European Working Group on Rett Syndrome, September 2009, Busto Arsizio, Italy, “Understanding MeCP2 targets through a combination of genomic and specific gene analyses.”

Research Funding Principal Investigator: The Role of MECP2 in Rett Syndrome, NICHD. 7/1/02 - 5/30/12, $210,995 annual direct. The major goals of this project are 1) to determine differences in subnuclear localization and differential protein association during neuronal maturation; 2) to investigate changes in nuclear protein association and subnuclear localization of MeCP2 target genes; and 3) to identify novel targets of MeCP2 by genomic chromatin immunoprecipitation approaches and test the relevance of each target gene to the pathogenesis of RTT.

Principal Investigator: Noncoding RNAs at the heart of Prader-Willi syndrome, NINDS, 7/1/11-6/30/16, $218,750 annual direct. The major goals of this proposal are 1) to determine the developmental roles of R-loop and host lncRNA cloud formations in chromatin dynamics of the Prader-Willi locus; 2) perform a transgenic rescue mouse experiment in a PWS mouse model; and 3) to perform a mouse/human comparative mechanistic analysis of PWS ncRNAs.

Community Service Epigenetic Mechanisms in Autism Spectrum Disorders, California EPA OEHHA Distinguished Lectures: Advances in Toxicology and Risk Assessment, Inaugural Series: Epigenetics and Environmental Diseases, Sacramento, CA, May 2008 Ad hoc reviewer for Nature Neuroscience, Nature Methods, Neuron, PLOS Genetics, Journal of Neuroscience, Journal of Biological Chemistry, Nucleic Acids Research, Neurobiology of Disease, Epigenetics, European Journal of Human Genetics, Journal of Medical Genetics, Journal of Molecular Medicine Ad hoc reviewer for Medical Research Council, Departmental of Defense Autism Concept Award Panel, Italian Telethon Foundation, Institut national de la sante et de la recharge medicale (INSERM), Autism Speaks Environmental RFA, International Rett Syndrome Foundation Appointed, European Science Foundation Pool of Reviewers Reviewer, Romanian Research Assessment Exercise Session Co-Chair, International Rett Syndrome Symposium Session Co-Chair, Epigenetics Platform Session, International Congress of Human Genetics

Awards and Honors Herbert and Esther Bennett Brandwein Award in Genetic Research International Rett Syndrome Foundation, Scientific Advisory Board (appointee) Dup15q Alliance, Professional Advisory Board (appointee)

______The MIND Institute______