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Full NameDr Gerard O'Keeffe
Department:Anatomy and Neuroscience
Organisation:University College Cork
- cell and developmental biology/regenerative medicine
- neuroscience and mental health
- Obstetrics and Gynaecology
- Child and Adolescent Psychiatry
Our central aim is to understand the factors important for brain health across the life-span in order to translate this information into new molecular therapies for neuroprotection and neuroregeneration. We are also interested in the molecular cross-talk between the brain and other physiological systems including the role of immune and placenta signals in regulating brain development.
Many of the molecular signals that are active during development can be utilised as therapies to protect the aging brain, so we also aim to use new understanding of molecular signalling to design and develop new therapies for neuroprotection in old age. We use an integrated approach that combines cell biology and bioinformatics approaches with in vivo modelling through to studies in humans. For selected examples of the types work see below.
O’Driscoll DJ, Felice VD, Kenny LC, Boylan GB, O'Keeffe GW. Mild prenatal hypoxia-ischemia leads to social deficits and central and peripheral inflammation in exposed offspring. Brain Behav Immun. 2018 Mar;69:418-427.
Straley ME, Van Oeffelen W, Theze S, Sullivan AM, O'Mahony SM, Cryan JF, O'Keeffe GW. Distinct alterations in motor & reward seeking behavior are dependent on the gestational age of exposure to LPS-induced maternal immune activation. Brain Behav Immun. 2017 Jul;63:21-34.
Title: Advancing Understanding of The Impacts of microRNA on ASD (AUTISMA).
Project: Autism Spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 59 children. Early intensive behavioural intervention can improve outcome, however, the narrow window available for effective intervention has often passed prior to diagnosis. Since 2008, the Cork BASELINE Birth Cohort study (www.baselinestudy.net) has followed mothers and their infants that were recruited at 20 weeks gestation. We have biobanked whole blood and serum from these children at birth. At 2 and 5 years we have studied their outcome using serial standardised developmental, behavioural and cognitive assessment. Any case of suspected ASD was confirmed by our local early intervention team.
miRNAs are small non-coding RNAs, that regulate gene expression by regulating specific mRNAs. Multiple miRNAs have been detected in the developing human brain and their predicted mRNA targets are implicated in ASD. miRNA’s are released by the cells in which they are formed, and circulate in the blood. There is early evidence that circulating miRNAs may be useful biomarkers in ASD. Studies of pre-pubertal children have shown altered expression of miRNAs in ASD samples. It is unknown if these altered miRNA profiles are present in younger children, or at birth. No previous study has examined miRNA profiling prior to ASD diagnosis.
Hypothesis: Differentially expressed circulating miRNAs are detectable at birth in children who progress to a diagnosis of ASD, and these will provide novel insight into the diagnosis and pathogenesis of ASD.
1. To determine the circulating miRNA expression profile at birth in children who progress to a diagnosis of ASD.
2. To identify the predicted downstream target genes and functional roles of those miRNAs clusters that are most altered in ASD.
Dr. Gerard O’Keeffe and Prof. Deirdre Murray, INFANT Centre, UCC and CUMH, Cork, Ireland.