Adrian Harwood

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 has 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 inDictyostelium, 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 Dictyostelium and 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 into the neurocellular basis of psychiatric disorders and the mechanism of action of mood stabilizers. I am a regular speaker at the BAP, CINP and ACNP, and a member of the CINP and Fellow of the Society of Biology (FSB).

Research Interest

Psychiatric disorders, such as schizophrenia, autism (ASD) and bipolar disorder are common, chronic conditions that contribute substantially to the global disease burden. Genetic studies are now identifying a series of genes that increase the risk of developing theses disorders. My research is aimed at understanding the neurocellular phenotypes of these genetic changes, with the aim of understanding the cell mechanisms underlying mental illnesses, and developing new therapeutic strategies. Current projects focus on mechanisms of epigenetic, cell signalling, cytoskeletal regulation and cell motility regulation that modulate cell behaviour and drug sensitivity. We are investigating three types of mechanism revealed through psychiatric genetics and use cell model systems that range from human stem cells to Dictyostelium. A number of epigenetic modulators have been associated with autism, schizophrenia and epilepsy. We are studying the effects of EHMT1 and the CHD family of proteins on neurodevelopment, gene regulation and cell behaviour. Genes encoding synaptic proteins that mediate glutamate and GABA signalling are associated with neuropsychiatric disorders, and we are using CRISPR technology in human stem cells to create new model systems for the study of these disorders and novel pharmacological intervention. Genes for the regulators of actin dynamics and cell adhesion are a third group associated with psychiatric conditions, and we are using neurocellular systems and Dictyostelium, a good model for chemotaxis, to establish cellular phenotypes and disease mechanism. Finally, we are studying the molecular mechanism of action of lithium and valproate, two widely used drugs in the treatment of bipolar mood disorder.