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Adrian Harwood  PhD, FRSB

Professor Adrian Harwood

PhD, FRSB

Co-Director of Research, Co-Director of the Neuroscience and Mental Health Innovation Institute

School of Biosciences

Email
HarwoodAJ@cardiff.ac.uk
Telephone
+44 29206 88492
Campuses
Hadyn Ellis Building, Room Room 3.33, Maindy Road, Cardiff, CF24 4HQ
Comment
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Overview

Research overview

I am neuro-cell biologist based in the Neuroscience and Mental Health Research Institute (NMHRI), and School of Biosciences. I have extensive experience in molecular signalling systems and cell analysis in neuronal and model cell systems.

My current work focuses on the molecular and cellular interactions that underlie genetic risk for psychiatric conditions and dementia. Current projects focus on cell signalling, synaptic function, neurodevelopment  and epigenetic mechanisms, and how they modulate neuronal and glial cell function and drug sensitivity. I am using human stem cell and CRISPR technologies to create new model systems for the study of neuropsychiatric disorders and their pharmacological analysis, and have developed human cell-based assays using Multi-Electrode Array techniques to monitor altered neuronal network activity arising from genetic mutation.  In doing so, my work aims to both develop new therapeutic strategies and provide basic insight into the cellular mechanisms underlying mental health.

Publication

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Patents

Research

Neurodevelopmental disorders (NDDs), such as schizophrenia and autism spectrum disorders (ASD) are common, chronic psychiatric conditions that contribute substantially to the global disease burden. Genetic studies are now identifying a series of genes that increase the risk of developing these conditions. Furthermore, considerable genetic risk also exists for the major conditions of bipolar disorder and dementia.  My research aims: to establish the neurocellular phenotypes arising from these genetic changes; to understand the mechanisms underlying the origins mental illness and to develop new therapeutic strategies. Current projects focus on epigenetic, neurodevelopmental and synaptic mechanisms associated with disease aetiology and drug action.

We are investigating three types of mechanism across a range of cell types differentiated from human induced pluripotent stem cells (iPSC). A number of epigenetic modulators have been associated with ASD, schizophrenia and epilepsy. We are studying the effects of EHMT1 and the CHD family of proteins on neurodevelopment, gene regulation and synaptogenesis. In addition to structural and metabolic process, certain lipids and fatty acids are essential for cell signalling. We are investigating the interaction of lipids and the bipolar risk gene Fatty Acid Desaturase 2 (FADS2) and their effects on stem cell proliferation, neurodevelopment and synaptic function.

Genes encoding synaptic proteins that mediate glutamate and GABA signalling are strongly associated with neuropsychiatric disorders. We are using combinations of CRISPR, genomic and Multi-Electrode Array (MEA) technology in human stem cells to create new model systems for the study of these disorders and novel pharmacological intervention.

Current grants

  • Wellcome Trust Strategic Award (WTSA): DEFINE: Defining Endophenotypes from Integrated Neurosciences.
  • The Waterloo Foundation:  Future minds
  • MINDDS (Maximising research Impacts for Neurodevelopmental Disorders). European COST Action
  • Cardiff University-Takeda Industrial Partnership

Collaborations

  • Jeremy Hall, NMHRI, Cardiff University
  • John Atack, Medicines Discovery Institute (MDI), Cardiff University
  • Julie Williams, UK Dementia Research Institute (DRI) Centre, Cardiff University
  • Vivi Heine, VU University Medical Center, Amsterdam
  • Patrick Sullivan, Karolinska Institutet, Stockholm.

Biography

Following my BA in Zoology from the University of Oxford, I investigated gene targeting by mitotic homologous recombination in cultured mammalian cells at the University of Edinburgh under the supervision of Chris Bostock, being awarded a PhD in 1988.

My further research focused on the study of signal transduction processes in the context of cell biology. Initially, I held a Research Fellowships at the ICRF Clare Hall Laboratories (1988-1991) in the group of Jeff Williams. During this period, I pioneered the study of cAMP-dependent protein kinase in Dictyostelium, establishing the basic role of this important kinase in spatial and temporal control during development. I also established a number of key technologies for Dictyostelium research, including the use of lacZ marker genes. I was awarded a MRC Post-doctoral Fellowship at the MRC Laboratory of Molecular Biology, Cambridge, (1992-1994) in the group of Rob Kay. Here, I carried out the first REMI mutagenesis screens outside the US, leading to discovering the essential role of GSK-3 in cell and developmental biology of Dictyostelium.

In 1995 I was awarded a Wellcome Trust Senior Biomedical Fellowship and established my own research group at the MRC Laboratory for Molecular Cell Biology (LMCB), holding a staff position in the Dept of Biology at University College London. I was promoted to Reader in 2001 and a personal chair in 2003. During this period, I continued to study GSK-3 signalling in Dictyostelium and developed an international reputation in the area of Wnt signaling. I discovered the first beta-catenin and the existence of adherens junctions outside the metazoa, published in Nature. In addition, my Cell paper on GSK-3 was a cornerstone for the discovery that lithium inhibits GSK-3. I have continued to investigate the role of lithium on cellular signaling pathways, investigating both GSK-3 and inositol phosphate signaling in both Dictyosteliumand neurons. My 2002 Nature paper is a seminal paper in the field of psychopharmacology, showing that inositol phosphate signaling is a common target of the majority of mood stabilizers.

In 2005, I moved to the School of Biosciences at Cardiff University, and was a co-founder of the University's Neuroscience and Mental Health Research Institute (NMHRI). I have continued to develop my research in on the neurocellular basis of psychiatric disorders and the mechanism of action of mood stabilizers, building a new group focussed on human iPSC.

Professional memberships

I am a member of the Collegium Internationale Neuro-Psychopharmacologicum (CINP), and a Fellow of the Royal Society of Biology (FSB), associate Editor of Molecular Biotechnology and an academic editor for Scientific Reports and an editorial board member of Cells.

Academic positions

Within the School of Biosciences, I was Group Leader of the Molecular Cell Biology Research Group (2005-2007) and Neuroscience (2011) was Head of Innovation, Partnership and Engagement from 2009-2013. I am currently co-Director of Research, and a co-Director of NMHRI.

I am also the Action Chair of the European COST Action CA16210 MINDDS

Committees and reviewing

I currently am a sift and interview panel member for the UKRI Future Leaders Fellowship programme and a member of the Network Advisory Group (NAG) of the UKRI-ESRC Mental Health networks.

I regularly referee grant applications for UK and international funders.