6875 Boulevard Lasalle
Researcher, Douglas Institute
Assistant Professor, Department of Psychiatry, McGill University
Canada Research Chair in Psychiatric Genetics - Tier 2
Genetic and epigenetic variation associated with neurodevelopmental disorders.
There are two main themes in the lab:
1) Identification of genetic variation associated with neurodevelopmental disorders. This involves recruiting patients and their families, collecting blood, skin, and possibly other tissue samples, and using high throughput technologies to identify genetic variation. We work collaboratively with families that choose to share their stories with us.
Generally, we receive referrals from Children's hospitals in Canada where current genetic analyses at these facilities have failed to identify any variant of interest. We take a comprehensive approach to each case. Once a genetic variant that might cause disease has been identified by our group, we convert patient skin cells to neurons using state-of-the-art stem cell biology techniques which allows us to study the function of the genetic variant in brain-like cells. Working closely with the Brain Bank at the Douglas hospital, we ask families to consider brain donation as well, depending on their own particular circumstances, which can significantly improve our understanding of the biology of neurodevelopmental disease.
2) Epigenetic studies of genomic regulation. Using human brain tissue, blood samples, or neural stem cells we study how modifications to the genome such as DNA methylation regulate gene expression patterns and cell function.
Blumenthal I., Ragavendran A., Erdin S., Klei L., Sugathan A., Guide J. R., Manavalan P., Zhou J. Q., Wheeler V. C., Levin J. Z., Ernst C., Roeder K., Devlin B., Gusella J. F., Talkowski M. E. (2014). Transcriptional consequences of 16p11.2 deletion and duplication in mouse cortex and multiplex autism families, Am J Hum Genet, 94(6), 870-83.
Chen E. S., Gigek C. O., Rosenfeld J. A., Diallo A. B., Maussion G., Chen G. G., Vaillancourt K., Lopez J. P., Crapper L., Poujol R., Shaffer L. G., Bourque G., Ernst C. (2014). Molecular Convergence of Neurodevelopmental Disorders, Am J Hum Genet.
Chen G. G., Diallo A. B., Poujol R., Nagy C., Staffa A., Vaillancourt K., Lutz P. E., Ota V. K., Mash D. C., Turecki G., Ernst C. (2014). BisQC: an operational pipeline for multiplexed bisulfite sequencing, BMC Genomics, 15, 290.
Nagy C., Suderman M., Yang J., Szyf M., Mechawar N., Ernst C., Turecki G. (2014). Astrocytic abnormalities and global DNA methylation patterns in depression and suicide, Mol Psychiatry.
Ernst C., Morton C. C. (2013). Identification and function of long non-coding RNA, Front Cell Neurosci, 7, 168.
Lindgren A. M., Hoyos T., Talkowski M. E., Hanscom C., Blumenthal I., Chiang C., Ernst C., Pereira S., Ordulu Z., Clericuzio C., Drautz J. M., Rosenfeld J. A., Shaffer L. G., Velsher L., Pynn T., Vermeesch J., Harris D. J., Gusella J. F., Liao E. C., Morton C. C. (2013). Haploinsufficiency of KDM6A is associated with severe psychomotor retardation, global growth restriction, seizures and cleft palate, Human genetics, 132(5), 537-52.
Lopez J.P., Mamdani F., Labonte B., Beaulieu M.M., Yang J.P., Berlim M., Ernst C., Turecki G. (2013). Epigenetic regulation of BDNF expression according to antidepressant response, Mol Psychiatry, 18(4), 398-9.
Ruderfer D.M., Chambert K., Moran J., Talkowski M., Chen E.S., Gigek C., Gusella J.F., Blackwood D.H., Corvin A., Gurling H.M., Hultman C.M., Kirov G., Magnusson P., O'Donovan M.C., Owen M.J., Pato C., St Clair D., Sullivan P.F., Purcell S.M., Sklar P., Ernst C. (2013). Mosaic copy number variation in schizophrenia, Eur J Hum Genet.
Canada Research Chair (Tier 2)
Tier 2 Chairs, tenable for five years and renewable once, are for exceptional emerging researchers, acknowledged by their peers as having the potential to lead in their field.
AFSP Young Investigator Award
This award is given by the American Foundation for Suicide Prevention (AFSP) to encourage talented new investigators to enter the field of suicide research through grants that provide training support and mentoring.
CIHR Bisby Award
In the news
Potential molecular consequences of transgene integration: The R6/2 mouse example. Sci Rep. 2017;7:41120.
Medium throughput bisulfite sequencing for accurate detection of 5-methylcytosine and 5-hydroxymethylcytosine. BMC Genomics. 2017;18(1):96.
Strategies to advance drug discovery in rare monogenic intellectual disability syndromes. Int J Neuropsychopharmacol. 2017.
Association of a History of Child Abuse With Impaired Myelination in the Anterior Cingulate Cortex: Convergent Epigenetic, Transcriptional, and Morphological Evidence. Am J Psychiatry. 2017:appiajp201716111286.
DNA Methylation Dynamics and Cocaine in the Brain: Progress and Prospects. Genes (Basel). 2017;8(5).
Implication of LRRC4C and DPP6 in neurodevelopmental disorders. Am J Med Genet A. 2017;173(2):395-406.
Cover Image, Volume 173A, Number 2, February 2017. Am J Med Genet A. 2017;173(2):i.
A Rapid Pipeline to Model Rare Neurodevelopmental Disorders with Simultaneous CRISPR/Cas9 Gene Editing. Stem Cells Transl Med. 2017;6(3):886-896.
Neurons diversify astrocytes in the adult brain through sonic hedgehog signaling. Science. 2016;351(6275):849-54.
A de novo frameshift mutation in chromodomain helicase DNA-binding domain 8 (CHD8): A case report and literature review. Am J Med Genet A. 2016;170A(5):1225-35.
Proliferation and Differentiation Deficits are a Major Convergence Point for Neurodevelopmental Disorders. Trends Neurosci. 2016;39(5):290-9.
Lesch-Nyhan Syndrome: Models, Theories, and Therapies. Mol Syndromol. 2016;7(6):302-311.
Characterizing 5-hydroxymethylcytosine in human prefrontal cortex at single base resolution. BMC Genomics. 2015;16:672.
Biomarker discovery: quantification of microRNAs and other small non-coding RNAs using next generation sequencing. BMC Med Genomics. 2015;8:35.
A molecular model for neurodevelopmental disorders. Transl Psychiatry. 2015;5:e565.
Astrocytic abnormalities and global DNA methylation patterns in depression and suicide. Mol Psychiatry. 2015;20(3):320-8.
Investigation of genes important in neurodevelopment disorders in adult human brain. Hum Genet. 2015;134(10):1037-53.
Comparative analysis of self-injury in people with psychopathology or neurodevelopmental disorders. Pediatr Clin North Am. 2015;62(3):619-31.
Transcriptional consequences of 16p11.2 deletion and duplication in mouse cortex and multiplex autism families. Am J Hum Genet. 2014;94(6):870-83.
BisQC: an operational pipeline for multiplexed bisulfite sequencing. BMC Genomics. 2014;15:290.
Molecular convergence of neurodevelopmental disorders. Am J Hum Genet. 2014;95(5):490-508.