A5069495397- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Receptor Mechanisms and Signaling
- Tryptophan and brain disorders
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Diet and metabolism studies
- Functional Brain Connectivity Studies
- Genetic Associations and Epidemiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Neuroendocrine regulation and behavior
- Birth, Development, and Health
- Hormonal Regulation and Hypertension
- Neuropeptides and Animal Physiology
- Bioinformatics and Genomic Networks
- Health, Environment, Cognitive Aging
- Migration, Health and Trauma
- Alzheimer's disease research and treatments
- Ion channel regulation and function
- Memory and Neural Mechanisms
- Signaling Pathways in Disease
- Neurogenesis and neuroplasticity mechanisms
- Neurotransmitter Receptor Influence on Behavior
- Posttraumatic Stress Disorder Research
The University of Sydney
2024-2025
McGill University
2024
Douglas Mental Health University Institute
2024
University of Wollongong
2014-2024
Max Planck Institute of Psychiatry
2016-2023
Illawarra Health and Medical Research Institute
2013-2023
UNSW Sydney
2015-2018
Schizophrenia Research Institute
2012-2018
Max Planck Society
2017
Identification and characterisation of novel targets for treatment is a priority in the field psychiatry. FKBP5 gene with decades evidence suggesting its pathogenic role subset psychiatric patients, potential to be leveraged as therapeutic target these individuals. While it widely reported that FKBP5/FKBP51 mRNA/protein (FKBP5/1) expression impacted by disease state, risk genotype age, not known which cell types sub-anatomical areas human brain this occurs. This knowledge critical propel...
Abstract Aging is a complex biological process and represents the largest risk factor for neurodegenerative disorders. The disorders also increased in individuals with psychiatric Here, we characterized age-related transcriptomic changes brain by profiling ~800,000 nuclei from orbitofrontal cortex 87 without diagnoses replicated findings an independent cohort 32 individuals. affects all cell types, LAMP5 + LHX6 interneurons, cell-type abundant primates, far most affected. Disrupted synaptic...
Alterations of postsynaptic density (PSD)95-complex proteins in schizophrenia ostensibly induce deficits synaptic plasticity, the molecular process underlying cognitive functions. Although some PSD95-complex have been previously examined hippocampus schizophrenia, status other equally important molecules is unclear. This especially true cornu ammonis (CA)1 hippocampal subfield, a region that critically involved pathophysiology illness. We thus performed quantitative immunoblot experiment to...
Exposure to chronic stress, either repeated severe acute or moderate sustained is one of the strongest risk factors for development psychopathologies such as post-traumatic stress disorder and depression. Chronic linked with several lasting biological consequences, particularly endocrine system but also affecting intermediate phenotypes brain structure function, immune behavior. Although genetic predisposition confers a proportion risk, most relevant molecular mechanisms determining those...
<h3>Background:</h3> Metabotropic glutamate receptors 2/3 (mGluR2/3) and 5 (mGluR5) are novel therapeutic targets for major depression (MD), bipolar disorder (BD) schizophrenia. We aimed to determine whether mGluR2/3 mGluR5 binding in the anterior cingulate cortex (ACC), a brain region essential regulation of mood, cognition emotion, were differentially altered these pathologies. <h3>Methods:</h3> Using postmortem human brains derived from 2 cohorts, [<sup>3</sup>H]LY341495...
Abstract Humanized mouse models can be used to explore human gene regulatory elements (REs), which frequently lie in non-coding and less conserved genomic regions. Epigenetic modifications of REs, also the context x environment interactions, have not yet been explored humanized models. We applied high-accuracy measurement DNA methylation (DNAm) via targeted bisulfite sequencing (HAM-TBS) investigate DNAm three tissues/brain regions (blood, prefrontal cortex hippocampus) mice carrying...
ABSTRACT An increasingly compelling body of literature indicates the glucocorticoid receptor cochaperone FK506-binding protein 51 (FKBP51) is a promising target for novel psychiatric therapeutics. However, mechanisms regulating corresponding FKBP5 gene directly in human brain remain largely unknown yet are needed to facilitate development precise mechanism-based treatment approaches. Here, we examined DNA methylation patterns postmortem samples from dorsolateral prefrontal cortex individuals...
Psychiatric disorders like schizophrenia, bipolar disorder, and major depressive disorder exhibit substantial genetic clinical overlap. However, their molecular architecture remains elusive due to polygenic nature complex brain cell interactions. We integrated data with susceptibility investigate gene expression chromatin accessibility in the orbitofrontal cortex of 92 postmortem human samples at single-nucleus (sn) level. Using snRNA-seq snATAC-seq, we analyzed ~800,000 400,000 nuclei,...
Background: Schizophrenia is a complex neuropsychiatric disorder with strong genetic component. Genome-wide association studies (GWAS) have identified numerous risk variants, but their functional impact on gene regulation remains largely unknown. A major challenge lies in interpreting the function of non-coding which comprise majority GWAS hits, making it difficult to determine consequences, particularly identifying target genes and cell types involved. Methods: We investigated disruption...
Abstract Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated psychiatric disorders, such as schizophrenia. mGluR1 mGluR5 expressed homodimers, which is important for their functionality pharmacology. We examined the protein expression of dimeric monomeric mGluR1α prefrontal cortex (PFC) hippocampus throughout development (juvenile/adolescence/adulthood) perinatal phencyclidine (PCP) model Under control conditions, dimer...
Severe stress exposure causes the loss of dendritic spines on cortical pyramidal neurons and induces psychiatric-like symptoms in rodent models. These effects are strongest following early-life most persistent apical dendrites. However, long-term impacts temporal human brain remain poorly understood. Using a novel postmortem cohort psychiatric cases with severe experienced childhood, adulthood, or no stress, matched controls, we aimed to determine impact timing neuron structure orbitofrontal...
Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex cleaves amyloid precursor protein. Alterations calcium (Ca2+) homeostasis and glutamate signaling are implicated pathogenesis FAD, however it has been difficult to assess humans whether or not these phenotypes result tau pathology. This study aimed early FAD measuring Ca2+ response induced pluripotent stem cell (iPSC)-derived neurons bearing ionotropic...