Annie Ciernia

 
Prospective Graduate Students / Postdocs

This faculty member is currently not actively recruiting graduate students or Postdoctoral Fellows, but might consider co-supervision together with another faculty member.

Assistant Professor

Research Interests

Autism
Brain development
Epigenetics
Gene-Environment Interactions
Neurodevelopmental disorders

Relevant Thesis-Based Degree Programs

Affiliations to Research Centres, Institutes & Clusters

Research Options

I am interested in and conduct interdisciplinary research.
 
 

Research Methodology

Next generation sequencing
animal behaviour
molecular biology
bioinformatics

Graduate Student Supervision

Master's Student Supervision

Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.

Inhibition of Hdac3 during immune stimulus ameliorates sex-specific depressive-like behaviour and aberrant microglial morphology in the amygdala (2023)

Major depressive disorder (MDD) or ‘depression’ is a common illness worldwide that affects 3.8% of the population. Globally, women are diagnosed with depression twice as often as men; an effect with both biological and socioeconomic underpinnings. Rodent models have elucidated various sex differences in the neurobiology of depression in the brain. Although brain inflammation is a hallmark symptom of depression in both human and rodent studies, none of the currently prescribed antidepressants target inflammation. In the brain, microglia are primary regulators of inflammation as they activate inflammatory machinery in response to environmental changes. Acutely, microglial responses are beneficial but chronic microglial- driven inflammation can lead to brain and behavioural impairment. Thus, untapped therapeutic potential lies in understanding the mechanistic switch between acute, beneficial responses and chronic, aberrant responses of microglia. One way that microglial activity is controlled is through epigenetic regulation of gene expression. Histone deacetylases (Hdacs) are one class of enzymes that control gene expression by removing acetyl groups from lysine residues on histone tails, facilitating DNA-histone contacts. Hdac3 is the most widely expressed Hdac in the brain, and pharmacological inhibition of Hdac3’s deacetylase activity has neuroprotective and functional recovery benefits in models of ischemic stroke and spinal cord injury. The current study aimed to investigate the sex-specific neuroprotective effects of Hdac3 inhibition during 5 days of lipopolysaccharide (LPS) immune challenge; a common mouse model of depression. Hdac3 inhibition during the LPS immune challenges ameliorated LPS-induced depressive like behaviour on the sucrose preference test in females and tail suspension test in males. Microglial morphology analysis demonstrated increased branching and junctions in the lateral and basolateral amygdala of female LPS-treated mice compared to PBS controls. This phenotype was rescued with RGFP966 treatment. Overall, this research demonstrates the neuroprotective effects of Hdac3 inhibition during a microglial-mediated neuroimmune response and presents Hdac3 as a potential epigenetic therapeutic target to control microglial function in MDD.

View record

Investigating the role of histone deacetylase 3 in microglial response to lipopolysaccharide (2022)

As the innate immune cell of the central nervous system, microglia play critical roles in the development and homeostasis of the brain. Microglia are active surveyors of their microenvironment and respond to pathogens through release of pro-inflammatory cytokines, phagocytosis of diseased or dying cells, and release of reactive nitrogen species. How microglia dynamically shift patterns of gene expression to respond to environmental cues is regulated by epigenetic mechanisms including the transcriptional activating modification histone acetylation. Histone acetylation disrupts chromatin contacts to increase accessibility of DNA to transcription factors and machinery at genomic regulatory regions including promoters (marked by H3K9ac) and enhancers (marked by H3K27ac). Dynamic regulation of histone acetylation is performed by ‘writer’ histone acetyltransferase (HAT) and ‘eraser’ histone deacetylase (HDAC) enzymes. Growing evidence supports therapeutic benefits of HDAC inhibition on dampening inflammatory processes, including Hdac3 inhibition in peripheral macrophages. This research aims to interrogate a possible immunomodulatory role of Hdac3 using an immortalized mouse microglial model through changes in global and promoter specific histone acetylation, gene expression, and microglia-relevant functions. To test this hypothesis, we utilized the BV2 microglia cell line combined with pre-treatment of a Hdac3-specific inhibitor (RGFP966) or pan-Hdac inhibitor (SAHA) followed by an immune stimulation of lipopolysaccharide (LPS). BV2 microglia treated with increasing durations of LPS (1, 3, 6, 24 hours) showed increased global histone acetylation of both H3K27 and H3K9, as well as increased expression of pro-inflammatory cytokines Il-6, Tnfa, Il-1b. Hdac inhibition of BV2 microglia resulted in increased global H3K27ac, indicating successful inhibition of Hdac activity. Furthermore, Hdac3-specific inhibition induced baseline increases in expression of pro-inflammatory cytokines Il-1b and Tnfa, as well as anti-inflammatory gene targets Cxcl16, Il-10, Arg1, and Tlr4. A subset of these genes were hyper-induced by Hdac3 inhibition after LPS stimulation. Functionally Hdac3-inhibition reduced LPS-induced nitric oxide production, suggesting an anti-inflammatory polarization of the microglia. Additionally, at 24 hours Hdac3 inhibition induced phagocytosis to similar levels as LPS treated microglia. Together, these results affirm Hdac3 as a valuable target for microglia immunomodulation, with possible therapeutic impacts such as dampening the release of neuroinflammatory reactive nitrogen species.

View record

 
 

If this is your researcher profile you can log in to the Faculty & Staff portal to update your details and provide recruitment preferences.

 
 

Read tips on applying, reference letters, statement of interest, reaching out to prospective supervisors, interviews and more in our Application Guide!