B.Sc. M.Sc. D.Phil.
- Associate Professor
- Supernumerary Fellow, University College
Understanding links between genes and brain dysfunction in psychiatric illness
My group's research aims to understand how individual genes impact on the complex brain functions that are altered in psychiatric disorders. I believe that understanding these links will help to explain why some people respond well to treatments, whilst others do not, and will ultimately lead to new and improved therapies.
In order to do this I use a wide range of experimental techniques, which allows me to study the function of these genes at all levels - from individual cells to the whole person. To achieve this, I collaborate with many other researchers within Oxford, elsewhere in the UK, and internationally.
My current research focuses on two main areas: the voltage-gated calcium channels (VGCCs) and the COMT gene.
In recent years, large-scale genetics studies have identified regions of the genome that are associated with risk for developing psychiatric disorders. The VGCC genes have emerged from these (and other) studies, as promising new drug targets for treating psychiatric illnesses. Calcium is an important signalling molecule in all cell types, and the VGCCs regulate its entry into electrically-active cells, like brain cells. My research investigates which VGCC subtypes are most relevant for psychiatric disorders. I am also exploring which VGCC subtypes are present in the brain, compared to the cardiovascular system, since brain VGCCs are likely to represent more selective drug targets for psychiatry.
In addition to my work on the VGCCs, I also have a strong interest in COMT. COMT influences the function of dopamine, a chemical messenger which is implicated in a number of psychiatric disorders and is critical to many different aspects of brain function in healthy people. We have shown that a drug that inhibits COMT increases dopamine levels in the brain and improves memory and attention. Most recently, we showed that a person’s genetic make-up determines whether the drug will improve memory or not. These findings show that inhibiting COMT could be beneficial for disorders in which patients suffer from problems with memory and attention, such as schizophrenia. They also emphasise that genetic factors can dramatically influence the response to a drug and suggest that in the future successful therapies may need to take a person’s individual genetic make-up into account. We are extending these findings by investigating COMT’s impact on brain functions beyond memory and attention, looking in particular their effect on people’s emotions and responses to rewards. In addition, we are also investigating how these links are altered by environmental factors, such as exposure to cannabis and stress.
We hope that by understanding the links between genes and psychiatric disorders we will not only shed light on the biological basis of these illnesses, but will also identify new treatment targets. My long-term goal is to use this knowledge to improve the lives of patients living with psychiatric disorders.
In addition to my research activities, I believe passionately in the importance of communicating the wonder and relevance of scientific advances as broadly as possible. I am privileged to have been awarded the Vice Chancellor's Award for Public Engagement in recognition of my work in this area, and to have been invited to give a TEDx talk as part of TEDx Whitehall 2018.
Currently, I am working with Eleanor Minney, a talented local artist, to develop artworks inspired my research. We are grateful to the Royal Society and the University of Oxford for funding our collaboration.