A.J. Harwood, Prof Dr

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.  Prof Harwood aims: to establish the neurocellular phenotypes arising from these genetic changes; to understand the mechanisms underlying the origins of mental illness and to develop new therapeutic strategies. This is primarily through patient iPSC-derived in vitro cell studies. Current projects focus on epigenetic, neurodevelopmental and synaptic mechanisms associated with disease aetiology and drug action.

He is investigating four types of mechanism across a range of cell types differentiated from human induced pluripotent stem cells (iPSC). Epigenetic modulators have been associated with ASD, schizophrenia and epilepsy. By studying the effects of EHMT1 and the CHD family of proteins on neural gene gene regulation and synaptogenesis, he is probing at the cell level the role of neurodevelopment in the origins of mental health. This has revealed the gene regulatory pathway mediated by miRNA that controls the timing of neuronal development.

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, an emerging area of psychiatric nutrigenomics.

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. This expertise has led to the creation of the spin-out company MeOmics.

Following a BA in Zoology from the University of Oxford, his early career research focussed on the technology development for the emerging field of molecular cell biology. He was awarded a PhD in 1988 from the University of Edinburgh for his investigation gene targeting by mitotic homologous recombination in cultured mammalian cells. During sequential Fellowships at the ICRF (1988-1991) and MRC Laboratory of Molecular Biology, Cambridge, (1992-1994), he applied these methods to the study of signal transduction processes in the context of cell biology, establishing the role of cAMP-dependent protein kinase in spatial and temporal control during Dictyostelium development. He carried out the first large scale Dictyostelium functional genomics screens outside the US, leading to discovering the essential role of GSK-3 in cell and developmental biology.

In 1995 he was awarded a Wellcome Trust Senior Biomedical Fellowship to establish his own research group at the MRC Laboratory for Molecular Cell Biology (LMCB), holding a staff position in the Department of Biology at University College London (UCL. He was promoted to a personal chair in 2003. During this period, he continued to study GSK-3 and its inhibition by lithium, extending these studies to other mood stabilizers and signal pathways. His 2002 paper investigating the relationship between antimanic and neuronal cell biology is a seminal paper in the field of psychopharmacology (ref)

In 2005, he moved to the School of Biosciences at Cardiff University and was a co-founder of the University's Neuroscience and Mental Health Innovation Institute (NMHII), where he is a NMHII co-Director. In 2024, he joined Maastricht University, and holds his second Chair as a member of TGX and MHeNs.