Annie Ciernia

PhD

Affiliate Investigator, BC Children's Hospital

Early life experience not only shapes our brains and behaviors, but impacts our risk for developing disease throughout our life. But how do our genes and environment combine to shape our developing brains? Epigenetic mechanisms that control the expression of genes without altering the underlying genetic code allow for cellular adaptation to a changing environment. These fundamental mechanisms control cellular differentiation, producing the vast diversity of cells in the body. They are also likely disrupted in many neurodevelopmental and neuropsychiatric disorders. The cause of neurodevelopmental disorders is complex and involves both genetic and environmental risk factors. A multitude of early-life environmental exposures and maternal health conditions increase the risk of neurodevelopmental disorders, including maternal immune activation and pollutant exposure during pregnancy. Disruption of epigenetic processes regulating brain developmental has been proposed as a potential mechanism linking environmental and genetic risk. The Ciernia laboratory combines experimental and computational approaches to understand how epigenetic mechanisms regulate gene expression across our lifespan. The lab specifically focuses on mechanisms of epigenetic regulation in multiple brain cell populations across normal brain and immune system development and in rodent models of neurodevelopmental disorders such as Autism Spectrum Disorders (ASD). We test novel hypotheses linking genetic and environmental risk factors to altered patterns of gene expression, epigenomic regulatory pathways, cellular function and animal behavior. Findings from our research will increase our understanding of the basic mechanisms regulating gene expression in the brain and form the basis for future development of novel immune targeted therapeutics for neurodevelopmental disorders such as ASD.

Academic Affiliations

  • Assistant Professor, , Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia
  • Research Theme: Healthy Starts
  • Research Group(s): Neurodevelopmental and Neurological Disorders; Origins of Child Health and Disease

Contact Information

Location

Room 4550, 2215 Wesbrook Mall, Djavad Mowafaghian Centre for Brain Health, Vancouver, British Columbia, Canada, V6T 2A1

Tau is necessary for Pseudomonas aeruginosa-induced blood-brain barrier dysfunction

Communications Biology

Samantha D. Chaney and Allison J. Bauman and Evan-Angelo R. Butlig and Sima Al-Masri and Juliana Montoya Sanchez and Lauren H. McAdams and Peter H. Doan and Meredith S. Gwin and Troy Stevens and Annie V. Ciernia and Mike T. Lin and Amy R. Nelson

DOI: 10.1038/s42003-026-09703-x

02 / 2026

Characteristics of early career health researchers and experiences of burnout during the COVID-19 pandemic in Canada

Sarah Hewko and Kaarina Kowalec and Laura Anderson and Erin E. Mulvihill and Maria J. Aristizabal and Annie V. Ciernia and Santokh Dhillon and Antoine Dufour and Gareth E. Lim and Maxime Rousseaux and Ayesha Saleem and Lubna Daraz and Grace Lam

DOI: 10.1101/2024.11.13.622718

11 / 2024

Early-Life Gut Inflammation Drives Sex-Dependent Shifts in the Microbiome-Endocrine-Brain Axis

Biorxiv

Sullivan, O. and Sie, C. and Ng, K.M. and Cotton, S. and Rosete, C. and Hamden, J.E. and Singh, A.P. and Lee, K. and Choudhary, J. and Kim, J. and Yu, H. and Clayton, C.A. and Carranza Garcia, N.A. and Voznyuk, K. and Deng, B.D. and Plett, N. and Arora, S. and Ghezzi, H. and Huan, T. and Soma, K.K. and Yu, J.-P.J. and Tropini, C. and Ciernia, A.V.

DOI: 10.1101/2024.05.23.595618

The Two Faces of HDAC3: Neuroinflammation in Disease and Neuroprotection in Recovery

Epigenomics

Rosete, C. and Ciernia, A.V.

DOI: 10.1080/17501911.2024.2419357

Restricting lysine normalizes toxic catabolites associated with ALDH7A1 deficiency in cells and mice

Cell Reports

Johal, A.S. and Al-Shekaili, H.H. and Abedrabbo, M. and Kehinde, A.Z. and Towriss, M. and Koe, J.C. and Hewton, K.G. and Thomson, S.B. and Ciernia, A.V. and Leavitt, B. and Parker, S.J.

DOI: 10.1016/j.celrep.2024.115069

Repeated LPS induces training and tolerance of microglial responses across brain regions

Biorxiv

Kim, J. and Sullivan, O. and Lee, K. and Jao, J. and Tamayo, J. and Madany, A.M. and Wong, B. and Ashwood, P. and Ciernia, A.V.

DOI: 10.1101/2024.04.08.588502

Impact of maternal immune activation and sex on placental and fetal brain cytokine and gene expression profiles in a preclinical model of neurodevelopmental disorders

Journal of Neuroinflammation

Osman, H.C. and Moreno, R. and Rose, D. and Rowland, M.E. and Ciernia, A.V. and Ashwood, P.

DOI: 10.1186/s12974-024-03106-7

Quantification of Global Histone Post Translational Modifications Using Intranuclear Flow Cytometry in Isolated Mouse Brain Microglia

Journal of Visualized Experiments

Towriss, M. and Kim, J. and Ciernia, A.V.

DOI: 10.3791/65080

Development of a high-throughput pipeline to characterize microglia morphological states at a single-cell resolution

Biorxiv

Kim, J. and Pavlidis, P. and Ciernia, A.V.

DOI: 10.1101/2023.11.03.565581

Modelling Microglial Innate Immune Memory In Vitro: Understanding the Role of Aerobic Glycolysis in Innate Immune Memory

International Journal of Molecular Sciences

Towriss, M. and MacVicar, B. and Ciernia, A.V.

DOI: 10.3390/ijms24108967

Insights Into the Emerging Role of Baf53b in Autism Spectrum Disorder

Frontiers in Molecular Neuroscience

Rowland, M.E. and Jajarmi, J.M. and Osborne, T.S.M. and Ciernia, A.V.

DOI: 10.3389/fnmol.2022.805158

Histone deacetylase 3 regulates microglial function through histone deacetylation

Biorxiv

Meleady, L. and Towriss, M. and Kim, J. and Bacarac, V. and Rowland, M. and Ciernia, A.V.

DOI: 10.1101/2022.09.08.507183

Dysregulated gene expression associated with inflammatory and translation pathways in activated monocytes from children with autism spectrum disorder

Translational Psychiatry

Hughes, H.K. and Rowland, M.E. and Onore, C.E. and Rogers, S. and Ciernia, A.V. and Ashwood, P.

DOI: 10.1038/s41398-021-01766-0

Work hard, play hard: how sexually differentiated microglia work to shape social play and reproductive behavior

Frontiers in Behavioral Neuroscience

Sullivan, O. and Ciernia, A.V.

DOI: 10.3389/fnbeh.2022.989011

MGEnrichment: a web application for microglia gene list enrichment analysis

Justin Jao and Annie Vogel Ciernia

DOI: 10.1101/2021.06.10.447854

06 / 2021

Chromatin Dynamics and Genetic Variation Combine to Regulate Innate Immune Memory.

Journal of clinical & cellular immunology

PubMed: 34295572

07 / 2020

Epigenomic Convergence of Neural-Immune Risk Factors in Neurodevelopmental Disorder Cortex

Cerebral Cortex

A Vogel Ciernia and B I Laufer and H Hwang and K W Dunaway and C E Mordaunt and R L Coulson and D H Yasui and J M LaSalle

DOI: 10.1093/cercor/bhz115

03 / 2020

Optogenetic intervention of seizures improves spatial memory in a mouse model of chronic temporal lobe epilepsy

Epilepsia

Hannah K. Kim and Tilo Gschwind and Theresa M. Nguyen and Anh D. Bui and Sylwia Felong and Kristen Ampig and David Suh and Annie V. Ciernia and Marcelo A. Wood and Ivan Soltesz

DOI: 10.1111/epi.16445

03 / 2020

Genetic variants drive altered epigenetic regulation of endotoxin tolerance in BTBR macrophages

Annie Vogel Ciernia and Verena M. Link and Milo Careaga and Janine LaSalle and Paul Ashwood

DOI: 10.1101/2020.02.08.940296

02 / 2020

Genetic variants drive altered epigenetic regulation of endotoxin response in BTBR macrophages

Brain, Behavior, and Immunity

Ciernia, A.V. and Link, V.M. and Careaga, M. and LaSalle, J.M. and Ashwood, P.

DOI: 10.1016/j.bbi.2020.05.058

Abstract # 3247 Genetic variants drive altered epigenetic regulation of endotoxin tolerance in BTBR macrophages

Brain, Behavior, and Immunity

A. Vogel Ciernia and M. Careaga and J. LaSalle and P. Ashwood

DOI: 10.1016/j.bbi.2019.08.042

10 / 2019

MeCP2 isoform e1 mutant mice recapitulate motor and metabolic phenotypes of Rett syndrome.

Human molecular genetics

DOI: 10.1093/hmg/ddy301 PubMed: 30137367

12 / 2018

Whole genome bisulfite sequencing of Down syndrome brain reveals regional DNA hypermethylation and novel disorder insights

Benjamin I. Laufer and Hyeyeon Hwang and Annie Vogel Ciernia and Charles E. Mordaunt and Janine M. LaSalle

DOI: 10.1101/428482

09 / 2018

Epigenetic regulation of the circadian gene Per1 contributes to age-related changes in hippocampal memory.

Nature communications

DOI: 10.1038/s41467-018-05868-0 PubMed: 30127461

08 / 2018

Microglia from offspring of dams with allergic asthma exhibit epigenomic alterations in genes dysregulated in autism

Glia

Annie Vogel Ciernia and Milo Careaga and Janine M. LaSalle and Paul Ashwood

DOI: 10.1002/glia.23261

03 / 2018

Experience-dependent neuroplasticity of the developing hypothalamus: integrative epigenomic approaches

Epigenetics

Annie Vogel Ciernia and Benjamin I . Laufer and Keith W. Dunaway and Charles E. Mordaunt and Rochelle L. Coulson and Theresa S. Totah and Danielle S. Stolzenberg and Jaime C. Frahm and Akanksha Singh-Taylor and Tallie Z. Baram and Janine M. LaSalle and Dag H. Yasui

DOI: 10.1080/15592294.2018.1451720

03 / 2018

Epigenetic regulation of the circadian gene Per1 in the hippocampus mediates age-related changes in memory and synaptic plasticity

Biorxiv

Kwapis, J.L. and Alaghband, Y. and Kram{\'a}r, E.A. and L{\'o}pez, A.J. and Ciernia, A.V. and White, A.O. and Shu, G. and Rhee, D. and Michael, C.M. and Montellier, E. and Liu, Y. and Magnan, C.N. and Sassone-Corsi, P. and Baldi, P. and Matheos, D.P. and Wood, M.A.

DOI: 10.1101/301135

MeCP2 isoform e1 mutant mice recapitulate motor and metabolic phenotypes of Rett syndrome

Biorxiv

Ciernia, A.V. and Yasui, D.H. and Pride, M.C. and Durbin-Johnson, B. and Noronha, A. and Chang, A. and Knotts, T. and Rutkowsky, J. and Ramsey, J.J. and Crawley, J.N. and LaSalle, J.M.

DOI: 10.1101/357707

UBE3A-mediated regulation of imprinted genes and epigenome-wide marks in human neurons.

Epigenetics

DOI: 10.1080/15592294.2017.1376151 PubMed: 28925810

11 / 2017

Snord116-dependent diurnal rhythm of DNA methylation in mouse cortex

Rochelle L. Coulson and Dag H. Yasui and Keith Dunaway and Benjamin I. Laufer and Annie Vogel Ciernia and Charles E. Mordaunt and Theresa S. Totah and Janine M. LaSalle

DOI: 10.1101/184788

09 / 2017

Early motor phenotype detection in a female mouse model of Rett syndrome is improved by cross-fostering.

Human molecular genetics

DOI: 10.1093/hmg/ddx087 PubMed: 28334953

05 / 2017

Mutation of neuron-specific chromatin remodeling subunit BAF53b: rescue of plasticity and memory by manipulating actin remodeling.

Learning & memory (Cold Spring Harbor, N.Y.)

DOI: 10.1101/lm.044602.116 PubMed: 28416631

04 / 2017

Cumulative Impact of Polychlorinated Biphenyl and Large Chromosomal Duplications on DNA Methylation, Chromatin, and Expression of Autism Candidate Genes.

Cell reports

DOI: 10.1016/j.celrep.2016.11.058 PubMed: 27974215

12 / 2016

The landscape of DNA methylation amid a perfect storm of autism aetiologies.

Nature reviews. Neuroscience

DOI: 10.1038/nrn.2016.41 PubMed: 27150399

05 / 2016

Visual Attention to Dynamic Scenes of Ambiguous Provocation and Children's Aggressive Behavior.

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53

DOI: 10.1080/15374416.2016.1138412 PubMed: 27027935

03 / 2016

Promoter-Specific Effects of DREADD Modulation on Hippocampal Synaptic Plasticity and Memory Formation.

The Journal of Neuroscience

DOI: 10.1523/JNEUROSCI.3682-15.2016 PubMed: 27013687

03 / 2016

Conserved higher-order chromatin regulates NMDA receptor gene expression and cognition.

Neuron

DOI: 10.1016/j.neuron.2014.10.032 PubMed: 25467983

11 / 2014

Examining object location and object recognition memory in mice.

Current protocols in neuroscience

DOI: 10.1002/0471142301.ns0831s69 PubMed: 25297693

10 / 2014

Reflexive orienting in response to short- and long-duration gaze cues in young, young-old, and old-old adults

Attention, Perception, and Psychophysics

Gayzur, N.D. and Langley, L.K. and Kelland, C. and Wyman, S.V. and Saville, A.L. and Ciernia, A.T. and Padmanabhan, G.

DOI: 10.3758/s13414-013-0554-6

Neuron-specific chromatin remodeling: a missing link in epigenetic mechanisms underlying synaptic plasticity, memory, and intellectual disability disorders.

Neuropharmacology

DOI: 10.1016/j.neuropharm.2013.10.002 PubMed: 24140580

10 / 2013

Targeting H3K4 trimethylation in Huntington disease.

Proceedings of the National Academy of Sciences of the United States of America

DOI: 10.1073/pnas.1311323110 PubMed: 23872847

07 / 2013

The neuron-specific chromatin regulatory subunit BAF53b is necessary for synaptic plasticity and memory.

Nature neuroscience

DOI: 10.1038/nn.3359 PubMed: 23525042

03 / 2013

Differential roles for Nr4a1 and Nr4a2 in object location vs. object recognition long-term memory.

Learning & memory (Cold Spring Harbor, N.Y.)

DOI: 10.1101/lm.026385.112 PubMed: 23161447

11 / 2012

Molecular brake pad hypothesis: pulling off the brakes for emotional memory.

Reviews in the neurosciences

DOI: 10.1515/revneuro-2012-0050 PubMed: 23096102

01 / 2012

Timing of reflexive visuospatial orienting in young, young-old, and old-old adults

Attention, Perception, and Psychophysics

Langley, L.K. and Friesen, C.K. and Saville, A.L. and Ciernia, A.T.

DOI: 10.3758/s13414-011-0108-8

Signatures of Microglial Dysfunction across Autism Spectrum Disorders (ASD) Models

Gene expression patterns and cellular morphology changes in human post-mortem ASD brain indicate increased microglial activation. However, it is unclear how changes in microglial function contribute to ASD, and if the observed immune signatures are a cause or consequence of altered brain development. To parse the role of microglia in ASD we are examining both genetic and environmental mouse models to address: When do microglial abnormalities arise during brain development? and How do altered microglial-neuronal interactions impact cellular development?
We hypothesize that the microglial transcriptome is altered in ASD mouse models across development and at least a subset of microglial genes are commonly disrupted across models. To test this hypothesis, we are examining changes in microglial gene expression and morphology from genetic and environmental ASD risk mouse models at multiple developmental timepoints. The long-term goal of this work is to identify common pathways of dysfunction that are conserved across different mouse models and in human ASD that can serve as novel biomarkers or therapeutic targets.

Epigenomic Regulation of Microglial Development

The goal of this project is to characterize and causally test the interplay of multiple epigenomic regulatory mechanisms in coordinating microglial maturation during normal brain development. During maturation microglia must coordinate specific patterns of gene expression for migration, differentiation, and establishment of a homeostatic state in the brain. This precise regulation of gene expression requires interactions with the maturing nervous system and is orchestrated by epigenetic mechanisms that allow both dynamic control of gene expression and stable, long-term cellular differentiation. We are utilizing a variety of epigenomic sequencing techniques combined with advanced bioinformatic and statistical modelling to understand microglial gene regulation across development.

Chromatin Remodeling in Neurodevelopmental Disorders

Mutations in 12 of the 29 subunit genes that compose the BAF (Brg1 Associated Factor) chromatin remodelling complex have been identified in ASD and Intellectual Disability, making it one of the most common genetically implicated protein complexes in neurodevelopmental disorders. However, it is unclear how mutations in this epigenetic regulator lead to childhood disorders. My lab is examining Baf53b, a subunit that confers neuronal specificity to the neuronal version of the BAF complex (nBAF). Baf53b is expressed exclusively in neurons and is only found within the nBAF complex, making it an ideal target for genetic manipulations to elucidate nBAF’s role in brain development. My lab will test the hypothesis that conditional deletion of Baf53b within specific neuronal populations during brain development in mice disrupts chromatin regulation. We will link the gene regulatory functions of nBAF to the development of relevant behaviours and deficits in neuronal connectivity and synapse maturation, allowing us to pinpoint the cell types, time points and gene targets regulated by nBAF. Our findings will provide mechanistic insight into a unique, neuronal epigenetic mechanism that is critical for normal brain development and highly relevant to therapeutic development for numerous childhood disorders including ASD, ID and epilepsy.

Grants

2019-2024: Canadian Institutes of Health Research. Tier 2 Canada Research Chair in Understanding Gene Expression in the Brain. Role: PI Salary Award

2019-2022: SickKids Foundation in partnership with the Canadian Institutes of Health Research. New Investigator Research Grant: The Role of Baf53b in Regulating Neuronal Gene Expression, Synaptic Function and Autism Behaviours Across Development. Role: PI

2019-2024: Canadian Foundation for Innovation. John R. Evans Leaders Fund. Role: PI

2019-2024: UBC Start-up Funding with the Department of Biochemistry and Molecular Biology and the Djavad Mowafaghian Centre for Brain Health. Role: PI

2019-2024: Natural Sciences and Engineering Council of Canada. Discovery Grant: Epigenomic Regulation In Microglia. Role: PI

2020-2021: DMCBH Kickstart Award. Pilot award for examining endotoxin tolerance using in vivo imaging. Role: PI

2019-2020: Natural Sciences and Engineering Council of Canada. Discovery Launch Supplement. Role: PI

2018-2019: Brain and Behavior Research Foundation. NARSAD Young Investigator Award: The Role of MeCP2 Isoform 1 in Rett Syndrome Disease Progression. Role: PI

2018-2019: National Institutes of Mental Health. Research Scientist Development Award: Mapping Multi-Omics Networks in Microglia Across Autism Models. Role: PI

Honours & Awards

2019: Cold Spring Harbor Laboratory Leadership in Biosciences course fellowship

2018: University of California Davis Postdoctoral Excellence in Research Award

2018: Postdoctoral Research Conference Oral Presentation Second Place Award

2017: Allen Brain Institute Summer Workshop on the Dynamic Brain Faculty Choice Award

2017: Allen Brain Institute Summer Workshop on the Dynamic Brain Fellowship

2017: UC Davis Postdoctoral Scholars Association Travel Award

2017: UC Davis Psychology Conference Oral Presentation Winner

2017: Postdoctoral Research Conference Oral Presentation Winner

2016: Helmsley Scholarship to attend Cold Spring Harbor Laboratory Statistical Methods for Functional Genomics workshop

2014: Autism Research Training Fellowship Program, University of California, Davis MIND Institute

2013: UCI Center for Cognitive Neuroscience and Engineering Graduate Merit Fellowship

2013: James L. McGaugh Award for Excellence in Graduate Research in Neurobiology and Behavior

2013: American College of Neuropsychopharmacology (ACNP) Travel Award

2013: Renee Harwick Advanced CNLM Graduate Student Award

2013: Top Graduate Oral Presentation at the 24th Science Conference of the Graduate Women in Science

2013: ReMIND Outstanding Presentation at the Emerging Scientist Symposium

2012: Second Prize Data Blitz at the CNLM Conference on the Neurobiology of Learning and Memory

2012: Achievement Rewards for College Scientists (ARCS) Fellowship ($20,000 award)

2012: Graduate Student Chapter Travel Award, Society for Neuroscience

2012-2013: Aging Training Grant (T32-AG00096-29)

2012: Roger Russell’s Scholar Award in The Neurobiology of Learning and Memory

2011: Graduate Fellow Award, HHMI-UCI Teaching Fellows Program

2011: Edward Steinhaus Teaching Award

2009-2010: Cellular and Molecular Neuroscience Training Grant (T32-NS007444)

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