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Dr William Davies

Dr William Davies

Senior Lecturer, Division of Psychological Medicine and Clinical Neurosciences

School of Medicine

School of Psychology

Email
daviesw4@cardiff.ac.uk
Telephone
+44 (0)29 2087 0152
Campuses
10.20, Tower Building, 70 Park Place, Cardiff, CF10 3AT
Users
Available for postgraduate supervision

Overview

Research themes: Neuroscience, Endocrinology and Genetics

I am interested in the (epi)genetic and endocrine mechanisms underlying sex differences in brain function and behaviour. My work focusses on the role of genes on the sex chromosomes (i.e. the X and Y), which are asymmetrically inherited between the sexes: females inherit two X chromosomes (one from each parent), whereas males inherit just one X chromosome (invariably from their mother) and a Y chromosome from their father. Principal aims of my research are: a) to understand why the sexes are differentially vulnerable to common and disabling developmental  disorders such as autism and ADHD, b) to understand the pathophysiology underlying psychological disorders associated with pregnancy and childbirth, and c) to help develop more effective sex-specific therapies.

As Human Tissue Officer for School of Psychology, and a member of the University's Human Tissue Research Governance Committee, I am responsible for ensuring that any research involving human tissue samples is conducted lawfully.

Location summary

I am based  in the Schools of Psychology (PSYCH) and Medicine (MEDIC) at Cardiff  University. I am a member of the Behavioural Genetics Group (PSYCH/MEDIC), the MRC Centre for Neuropsychiatric Genetics and Genomics (MEDIC), the Division of Psychological  Medicine and Clinical Neurosciences (MEDIC) and the Neuroscience and Mental Health Research Institute (PSYCH/MEDIC).

Teaching summary

PSYCH

  • Module Co-ordinator (Biological Psychology and Individual Differences)
  • Deputy Module Co-ordinator (Behavioural Genetics)
  • Year 2 Developmental Psychology Practical Supervisor
  • Personal and Academic Tutor
  • Final Year Project Supervisor

MEDIC

  • Year 1 Case-based Learning Facilitator
  • Platform for Clinical Sciences Facilitator
  • Lecturer (The Scientific Basis of Psychological Medicine)
  • Intercalated B.Sc in Psychology Lecturer and Project Supervisor
  • Personal and Academic Mentor

PSYCH/MEDIC

  • Ph.D Supervisor and Mentor

Biography

Undergraduate education

  • M.Biochem (1st Class) Hons. (University of Bath)

Postgraduate education

  • Ph.D (Behavioural Neuroscience) (University of Cambridge)
  • Postgraduate  Certificate in University Teaching and Learning (Module 1) (Cardiff University)

Employment

  • 2012-present:  Senior Lecturer, Cardiff University, UK
  • 2007-2012: RCUK Fellow, Cardiff University, UK
  • 2006-2007: Wellcome Trust 'Value in People’ Fellow, Cardiff University, UK
  • 2003-2006: Postdoctoral scientist, The Babraham Insitute, Cambridge, UK

Honours and awards

Awards/external committees

  • Associate Editor: Frontiers in Neurogenomics
  • Editorial Board member: Endocrinology, World Journal of Psychiatry
  • British Council Biological and Medical Sciences Review Panel member
  • Genetics Society Cardiff University representative
  • Fellow, Higher Education Academy
  • 'Excellence in Undergraduate Teaching' Award (2020)
  • EMBL Workshop Fellowship
  • Winner, National Brain-Science Writing Prize (Researcher category)
  • The Florence P. Haseltine Award for Outstanding Poster Presentation, 6th Annual Sex and Gene Expression Conference,Winston-Salem, USA
  • British Neuroscience Association Postgraduate Prize
  • Oon Khye Beng Ch’hia Tsio Studentship for Preventive Medicine, Downing College, University of Cambridge

Publications

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2019

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1999

Research topics and related papers

Our work employs a wide variety of experimental techniques including: operant and spontaneous assays of behaviour in rodents, anatomical and biochemical analysis of body tissues, assays of gene and protein expression, measurement of endocrine markers, genetic modification and genetic analysis, neuropsychological testing, and online survey approaches.

1. The role of steroid sulfatase in brain and behavioural phenotypes in man and mouse

Our previous work in mice and humans has suggested that the X-linked gene STS, which encodes the neurosteroid-modulating enzyme steroid sulfatase, may influence a wide range of cognitive and behavioural functions, notably attention. Ongoing work in rodent models and clinical populations aims to further specify psychological processes that are sensitive to the effects of steroid sulfatase (dys)function, and to clarify the neurobiological mechanisms through which steroid sulfatase (dys)function may impinge upon cognitive processes. This work is of direct relevance to the rare disorder X-linked ichthyosis (caused by steroid sulfatase deficiency), and may also shed light upon the mechanisms underlying idiopathic developmental disorders and postpartum mood disorders.

Medical and neurobehavioural phenotypes in X-linked ichthyosis associated genetic deletion carriers in the UK Biobank: Brcic et al. (2020) Journal of Medical Genetics 0:1–7. doi:10.1136/jmedgenet-2019-106676; lay summaries of this paper available here and here

A short video on our work examining the association between behaviour and mental health and X-linked ichthyosis: https://www.youtube.com/watch?v=9YRhGK8Qp0c

Behaviour and mental health in female carriers of genetic mutations associated with X-linked ichthyosis: Cavenagh et al. (2019) PLoS ONE 14(2):e0212330

STS, maternal behaviour and mental health: Davies (2018) Journal of Molecular Endocrinology 61(2):T199-T210

STS deficiency and psychosis: Malik et al. (2017) Journal of Medical Case Reports 11(1):267

Genetic variation in STS and cognition in healthy males: Humby et al. (2017) Brain and Behavior 7(3):e00646

Behaviour and mental health in males with X-linked ichthyosis: Chatterjee et al. (2016) PloS ONE 11(10):e0164417

STS deficiency and response inhibition in mice: Davies et al. (2014) Neuropsychopharmacology (2014) 39(11):2622-32

STS deficiency and brain gene expression and neurochemistry in mice: Trent  et al. (2014) Molecular Autism 5(1):21

STS deficiency and hippocampal function in mice: Trent et al  (2013) Psychoneuroendocrinology 38(8):1370-80

STS deficiency and neurochemistry in mice: Trent et al (2012) Neuropsychopharmacology 37(5):1267-74

STS deficiency and behaviour in mice: Trent et al (2012) Psychoneuroendocrinology 37(2):221-9

Genetic variation in STS and symptoms and cognition in boys with ADHD: Stergiakouli et al (2011) Genes Brain & Behavior 10(3):334-44

STS deficiency and attention in mice: Davies et al (2009) Biological Psychiatry 66(4):360-7

2.  Genetic and endocrine mechanisms underlying sex differences in brain development, behaviour and physiology

Females inherit two X chromosomes (one from each parent) whereas males inherit a single X chromosome (invariably from their mother) and a Y chromosome from their father. This asymmetry of inheritance across the genders gives rise to three main genetic mechanisms that could either underpin male-female differences in  physiology directly, or via effects on hormones including androgens and oestrogens: i) expression of Y-linked genes in males only (including the testis-determining  gene SRY), ii) higher expression of X-linked genes which escape X-inactivation  in female tissues, and iii) differential expression of X-linked genes that are subject to the epigenetically-mediated process of genomic imprinting. Our collaborative work, in rodent models (e.g. 39,XO mouse and Four Core Genotypes  model), in clinical populations, and in healthy participants and tissues aims to investigate the extent and specificity with which each of these three mechanisms contributes to sex differences in physiology. This work is likely to inform our understanding of the molecular pathophysiology underlying sex chromosome aneuploidies such as Turner and Klinefelter syndromes, and sex-biased developmental disorders such as ADHD and autism.

Sex differences in gene expression in human fetal brain: O'Brien et al. (2019) bioRxiv https://doi.org/10.1101/483636

Early-life androgen exposure and religiosity: Richards et al. (2018) Transpersonal Psychology Review 20(1):23-36

Familial patterns of a somatic marker of early-life androgen exposure: Richards et al. (2017) Early Human Development 112:14-19

A review of the overlap between RASopathies and Turner syndrome: Green et al. (2017) Journal of Neurodevelopmental Disorders 9:25

X chromosome effects on cardiac morphology in mice: Hinton.et  al. (2015) Journal of Cardiovascular Development and Disease 2(3):190-199

Genetic and endocrine mechanisms influencing ADHD risk: Davies (2014) Frontiers in Neuroendocrinology 35(3):331-46

Sex chromosome complement and endocrine effects on behaviour in mice: Kopsida et  al (2013) PLOS ONE 8(8):e73699

Investigating sex-linked genetic effects on behaviour in mice: Davies  (2013) Brain Research Bulletin 92:12-20

A review of sex-linked effects on attention and impulsivity: Trent & Davies (2012) Biological Psychology 89(1):1-13

The Y chromosome and brain function: Kopsida et al (2009) The Open Neuroendocrinology Journal 2: 20-30

Brain and behavioural phenotypes in the 39,XO mouse: Lynn et al (2007) Behavioural Brain Research 172(2):173-182

X-monosomy effects on attention in mice: Davies et al (2007) Biological  Psychiatry 61(12):1351-1360

Brain and behavioural effects of X-linked imprinted genes: Davies et al (2006) BioEssays 28(1):35-44

A review of gonadal hormone-independent sex-linked genetic effects on brain and behaviour: Davies & Wilkinson (2006) Brain Research 1126(1):36-45

An X-linked parent-of-origin cognitive effect in mice and a new candidate X-linked imprinted gene: Davies et al (2005) Nature Genetics 37(6):625-629

X-monosomy effects on anxiety-related behaviour in mice: Isles et al (2004) Human Molecular Genetics 13(17):1849-1855

3. Understanding the biological basis of postpartum mood disorder risk

New mothers can be affected by a number of psychiatric conditions which range in severity and prevalence. We are particularly interested in postpartum psychosis (PP), a rare but extremely serious psychiatric disorder affecting mothers shortly after childbirth and characterised by delusions, mood swings, anxiety and cognitive disorganisation. Despite its severity, the neurobiology underpinning PP risk is very poorly-understood, partially as a consequence of not having suitable animal models available. Our work in rodent models and clinical populations aims to identify and characterise plausible biological risk pathways for PP, ultimately with a view to developing better treatments and predictive biomarkers.

A new molecular risk pathway for postpartum mood disorders: clues from steroid sulfatase-deficient individuals Thippeswamy & Davies (2020) Preprint

CCN proteins as candidate mediators of postpartum mood disorder risk Davies (2019) Frontiers in Psychiatry 10:876

Brain gene expression in a novel mouse model of postpartum mood disorder: Humby & Davies (2019) Translational Neuroscience 10:168-174

A new hypothesis for postpartum psychosis risk: Dazzan et al. (2018) Trends in Molecular Medicine 24(11):26-34

STS, maternal behaviour and mental health: Davies (2018) Journal of Molecular Endocrinology 61(2):T199-T210

Investigating the pathophysiology of postpartum psychosis: Davies (2017) World Journal of Psychiatry 7(2):77-88

A new mouse model of postpartum psychosis: Humby et al. (2016) Psychoneuroendocrinology 74:363-370

STS deficiency and postpartum psychosis: Davies (2012) Trends in Molecular Medicine 18(5):256-62

4. Developing rodent tasks of cognition: understanding sex differences in gambling behaviour

We have developed a number of new operant tasks to assess cognition in rodents, many of which are analogues of neuropsychological tasks used to assess cognition in humans, and several of which have now been adapted for use with touchscreen apparatus to allow sophisticated stimulus presentation. We are currently interested in using these tasks to understand the biological basis of  gambling predisposition, and in particular, to understand why the prevalence of gambling behaviour, and the progression to pathological gambling, differs between males and females.

A new mouse behavioural assay of gambling behaviour and effects of serotonergic and cognition-enhancing drugs: Humby et al. (2020) Psychopharmacology doi: 10.1007/s00213-020-05496-x

Investigating factors influencing gambling proneness: Van den Bos et al. (2013) Neuroscience and Biobehavioral Reviews 37(10):2454-71

A new mouse behavioural assay of attention: Humby et al. (1999) European Journal of Neuroscience 11(8):2813-23

5. Investigating links between immune system manipulation and brain and behaviour

Many psychiatric and neurological disorders are associated with changes in the immune system function; however, the link between immune system changes and brain/behavioural function is only just beginning to be clarified. We are interested in the role of a particular type of immune cell (regulatory T-cells, Tregs) on brain and behaviour. Tregs are immunosuppressive, and can also stimulate myelination processes - we suspect that their depletion will result in phenotypes associated with mood and psychotic disorders (including in the postpartum period), and are using mouse models to address this hypothesis. 

6. Testing new  genetic rodent models of psychiatric disorder: the impact of sex

I am co-supervisor or Ph.D mentor for numerous projects examining the behavioural and cognitive effects of manipulating genetic risk loci for psychiatric disorders (notably ZNF804A/Zfp804a, Cyfip1, Fmr1, Setd1a and Cacna1c) in rodent models; I am particularly interested in whether these manipulations give rise to sex-specific effects and whether they can shine a light upon biological mechanisms which act to mediate the 'female protective effect’ against  developmental disorders.

Funding

MRC Centre for Neuropsychiatric Genetics and Genomics Co-PI (£3.4M)

Wellcome Trust Integrative Neuroscience Ph.D scheme Co-PI (£2.3M)

MRC New Investigator Research Award (£430K)

Research Councils UK Fellowship in Translational Research in Experimental Medicine (£125K)

MRC Centre for Neuropsychiatric Genetics and  Genomics and Neuroscience and Mental Health Research Institute Seedcorn Funding  (£10K)

Research group

I work closely with the other PIs within the  Behavioural Genetics Group at Cardiff University, and supervise, co-supervise and mentor, numerous graduate and undergraduate students within this group.

Research collaborators

Dr Trevor Humby and Professor Lawrence Wilkinson (Cardiff University, UK)

Jack Underwood, Kimberley Kendall, Xavier Caseras and George Kirov (Cardiff University, UK) 

Professor Andrew Thompson (Cardiff University, UK)

Professor Awen Gallimore (Cardiff University, UK)

Dr Evangelia Stergiakouli (University of Bristol, UK)

Professor Paola Dazzan and Dr Monserrat Fuste-Boadella (Institute of  Psychiatry, Psychology and Neuroscience, Kings College London, UK)

Dr Gareth Richards (University of Newcastle, UK)

Dr James Turner and Mr Obah Ojarikre (Crick  Institute, UK)

Dr Tamar Green (Stanford University, USA)

Dr Wafaa Eyaid (King Abdullah International Medical  Research Center, Saudi Arabia)

Professor Dan Rujescu (University of Halle,  Germany)

Dr Tommaso Cassano (University of Foggia, Italy)

Supervision

Postgraduate research interests

We are interested in how, and why, the genders differ in terms of their behaviour and in their vulnerability to different psychological conditions. We are especially interested in understanding the biological mechanisms underpinning risk of developmental disorders such as ADHD and autism (which are diagnosed far more frequently in males than females) and pregnancy and childbirth-related psychiatric disorders such as postpartum psychosis, which affects women shortly after childbirth.

We use a wide variety of experimental approaches in rodent models and in healthy and clinical human populations, and focus particularly upon the brain and  behavioural effects of genes on the sex chromosomes (i.e. the X and Y) which  are asymmetrically inherited between males and females.

These studies may have important implications for understanding why men and women behave differently, for why the genders are differentially vulnerable to certain disorders, and for developing more effective sex-specific therapies and biomarkers.

If you are interested in applying for a PhD, or for further information regarding my postgraduate research, please contact me directly (contact details available on the 'Overview' page), or submit a formal application.

Current students

Georgina Wren: 'Psychological issues in congenital skin disorders'

Eleanor Bird: 'Investigating links between regulatory T-cell depletion and psychosis'

Past projects

Phoebe Lynn: 'The influence of sex-linked genetic  mechanisms on brain and behaviour in mice’

Eleni Kopsida: 'Behavioural effects of manipulations of the Y-linked Sry gene in rodents’