Download BIOGRAPHICAL SKETCH Janine M. LaSalle, Ph. D. Professor

Principal Investigator/Program Director (Last, First, Middle):
BIOGRAPHICAL SKETCH
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NAME
POSITION TITLE
Janine M. LaSalle, Ph. D.
Professor
eRA COMMONS USER NAME
jmlasalle
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
Randolph-Macon College, Ashland, VA
Harvard University, Boston, MA
HHMI, Children’s Hospital, Harvard Medical
School, Boston, MA
A. Personal Statement
DEGREE
(if applicable)
B.S.
Ph.D.
Postdoctoral
YEAR(s)
1988
1993
1993-96
FIELD OF STUDY
Biology
Immunology
Human Genetics
The goal of the proposed research is to investigate epigenetic etiologies of human autism spectrum
disorders, particularly associated with human chromosome 15q11-13. I have been involved since my
postdoctoral training at Harvard in innovative research understanding chromatin dynamics of the 15q11-13
region and its relevance to parental imprinting and human neurodevelopmental disorders. Over the past
13 years, my laboratory has performed pioneering research in the emerging field of “Autism Epigenetics”
by demonstrating overlapping pathways of gene dysregulation between Rett syndrome, 15q11-13
deletion/duplication disorders, and idiopathic autism. We have pioneered the use of human postmortem
brain samples for epigenetic studies through a variety of novel methodologies including laser scanning
cytometry, tissue microarrays, fluorescence in situ hybridization, and DNA methylation analyses to
demonstrate overlapping epigenetic defects in multiple disorders. We were the first to perform combined
epigenomic analyses of MeCP2 and DNA methylation of promoters genome-wide in a human neuronal cell
line. The proposed studies expand upon the epigenomic analyses of cell lines and autism post-mortem
brain samples. In summary, I have demonstrated a productive track record in the challenging but
emerging field of autism epigenetics and my expertise and experience make me uniquely qualified for the
proposed project.
B. Positions and Honors
Professional Background
1996-1997
Instructor of Pediatrics, Genetics Division
Children's Hospital, Harvard Medical School
1997-2003
Assistant Professor, Medical Microbiology and Immunology, Rowe Program in Human
Genetics, School of Medicine, University of California, Davis
2003-2007
Associate Professor, Medical Microbiology and Immunology, Rowe Program in Human
Genetics, School of Medicine, University of California, Davis
2007-present
Professor, Medical Microbiology and Immunology, Rowe Program in Human Genetics,
School of Medicine, University of California, Davis
Honors, Awards, Professional Memberships, and Scientific Committees
1988
Magna Cum Laude, Phi Beta Kappa
1988
National Science Foundation graduate fellowship
1993
Clinical Immunology Society, Science Recognition Award for New Investigators
1993
Howard Hughes Medical Institute postdoctoral fellowship
1994
American Society of Human Genetics, Award Recipient for Postdoctoral Basic Research
1999
March of Dimes, Basil O’Connor Award
1999-present
American Society of Human Genetics
PHS 398/2590 (Rev. 09/04)
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Principal Investigator/Program Director (Last, First, Middle):
2003-present
2005-2010
2006-present
2007-present
2008-present
2009-present
2009-present
2009-present
2009-present
2009-present
2010
International Society for Autism Research
Member, Developmental Brain Disorders Study Section, NIH
Editorial Board, Human Molecular Genetics
Society for Neuroscience
IDEAS Professional Advisory Board (Isodicentric 15 Exchange, Advocacy & Support)
Editorial Board, Molecular Autism
Scientific Advisory Board, International Rett Syndrome Foundation
European Science Foundation Pool of Reviewers
UC Davis Genome Center, full member
NICHD National Children’s Study, Autism Speaks subgroup on environmental exposures
Children’s Hospital of Philadelphia, Center for Autism Research, Distinguished Lecture
C. Selected peer-reviewed publications
15 most relevant publications (selected from 51)
LaSalle JM and M. Lalande, 1996. Homologous association of oppositely imprinted chromosomal domains.
Science. 272:725-728. PMCID: 8614834
LaSalle JM., R. Ritchie, H. Glatt, and M. Lalande. 1998. Clonal heterogeneity at allelic methylation sites
diagnostic for Prader-Willi and Angelman syndromes. Proc. Natl. Acad. Sci. 95:1675-1680. PMCID:
9465075
Balmer D and LaSalle JM. 2001. Clonal maintenance of imprinted expression of SNRPN and IPW in normal
lymphocytes: Correlation with allele-specific methylation of SNRPN intron 1 but not intron 7. Hum.
Genet.;108:116-122. PMCID: 11281449
Balmer D, Arredondo J, Samaco RC, and LaSalle JM. 2002. MECP2 mutations in Rett syndrome adversely
affect lymphocyte growth but do not affect imprinted gene expression in blood or brain. Hum. Genet.,
110:545-552. PMCID: 12107440
Samaco RC, Nagarajan RP, Braunschweig D, and LaSalle JM. 2004. Multiple pathways regulate MeCP2
expression in normal human brain development and exhibit defects in autism-spectrum disorders. Hum.
Mol. Genet. 13:629-639. PMCID: 14734626
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. PMCID: 15615769
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. PMCID: 15689352
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.
PMCID: 17486179
Hogart A, Nagarajan RP, Patzel KA, Yasui DH, LaSalle JM. 2007. 15q11-13 GABAA receptor genes are
normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum
disorders. Hum. Mol. Genet. 16:691-703. PMCID: 17339270
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. PMCID: 18042715
Wang NJ, Parokonny AS, Thatcher KN, Driscoll J, Malone BM, Sigman M, LaSalle JM, Schanen NC. 2008.
Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15, BMC
Genetics, 9:2. PMCID: 18177502
Hogart A, Patzel KA, and LaSalle JM. 2008. Gender influences monoallelic expression of ATP10A in human
brain. Hum. Genet., 124:235-242. PMID: 18726118, NIHMSID # 88432, in process
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., 46:86-93. PMCID: 18835857
Swanberg SE, Nagarajan RP, Peddada S, Yasui DH, LaSalle JM. 2009. Reciprocal co-regulation of EGR2
and MECP2 is disrupted in Rett syndrome and autism. Hum. Mol Genet. 18:525-534. PMCID: 19000991
Leung KN, Vallero RO, DuBose AJ, Resnick JL, LaSalle JM. 2009. Imprinting regulates mammalian snoRNAencoding chromatin decondensation and neuronal nucleolar size. Hum. Mol. Genet., 18:4227-4238.
PMCID: 19656775
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Principal Investigator/Program Director (Last, First, Middle):
D. Research Support.
Active
Epigenetic etiologies of autism-spectrum disorders
P.I., J.M. LaSalle
NIH 1R01HD048799
8/10/05 to 5/30/10 (3/1/10 to 2/28/10 no cost extension)
The major goals of this project are 1) to determine the effect of MeCP2 on gene expression within 15q11-13; 2)
to determine the mechanism by which MeCP2 organizes and regulates gene expression within 15q11-13; 3) to
screen for defects in MeCP2 and 15q11-13 gene expression in autism brain samples.
Epigenetic Interaction of MECP2 and Organic Pollutants in Neurodevelopment
P.I., J. M. LaSalle
NIH 1R01ES015171
9/21/06 to 8/30/10
The major goals of this project are 1) to investigate behavioral effects of perinatal exposure to PCB 95 and
PBDE 47 in wild-type and Mecp2308 mice; 2) to investigate epigenetic effects on expression levels of MECP2,
UBE3A, and GABRB3; 3) to investigate epigenetic alterations in brain and blood samples from children with
autism and mental retardation and correlate with levels of POPs; 4) test the heritability of epigenetic alterations
caused by POP exposure.
The Role of MECP2 in Rett Syndrome
P.I., J. M. LaSalle, Ph.D.
NIH 2R01HD041462
7/1/02 to 3/31/12
The major goals of this project are 1) determine dynamic changes in sub-nuclear localization, protein
association, and post-translational modifications and differences between MeCP2e1 and MeCP2e2 isoforms;
2) investigate dynamic developmental changes in nuclear protein association and sub-nuclear localization of
MeCP2 target genes; 3) identify novel target genes of MeCP2 by a genomic ChIP-chip approach and test their
relevance to the pathogenesis of RTT.
Interdisciplinary Training for Autism Researchers
P.I., S.L. Rogers, Ph.D.
T32 MH73124
Faculty trainer, J.M. LaSalle, Ph.D
NIH Kirschstein-NRSA postdoctoral training grant
9/29/04 – 7/31/14
The M.I.N.D. Institute at the University of California-Davis is offering a postdoctoral training program to
prepare Ph.D. and M.D. fellows for careers in autism research. The goal of this program is to train truly
interdisciplinary autism research scientists. The M.I.N.D. Institute and UC Davis provide a unique environment
for conducting postdoctoral research on aspects of autism.
Past three years
The Role of MECP2 in Rett Syndrome
P.I., J. M. LaSalle, Ph.D.
Autism Speaks Bridge Funding Award
02/01/08 to 1/31/09
The major goals of this project are to determine dynamic changes in sub-nuclear localization, protein
association, and post-translational modifications and differences between MeCP2e1 and MeCP2e2 isoforms.
Investigation of Novel MeCP2 Target Genes Regulating Neuronal Maturation
P.I., J.M. LaSalle
Rett Syndrome Research Foundation
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Principal Investigator/Program Director (Last, First, Middle):
10/1/05 to 9/30/08
The major goals of this project are 1) to characterize the effect of MeCP2 deficiency on the ID family of
transcriptional regulators; 2) to determine the functional relevance of ID regulatory proteins to the
pathogenesis of Rett syndrome.
iCys Laser Scanning Cytometer for UC Davis Core
P.I., J. M. LaSalle
NIH 1S10RR024747
05/01/08 to 04/31/09
This is a shared instrumentation grant to support the purchase of the next generation laser scanning cytometer
for the UC Davis core facility.
Epigenetics of X-linked Genes in PBC: Does X Mark the Spot?
P.I., C. Selmi
Collaborator, J.M. LaSalle
NIH 1R21 DK075400-01
7/01/06 to 6/30/09
The major goals of this project are 1) to determine if altered expression of 125 differentially inactivated X-linked
genes are found in monozygotic female twins discordant for the autoimmune disorder primary biliary cirrhosis
(PBC); 2) to determine the methylation patterns of X-linked genes differentially expressed in affected and
unaffected twins by bisulfite sequencing.
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