GSFL:Research Projects

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We are interested in the application of genetics to the understanding and treatment of disease. Our main research themes are psychiatric genetics and pharmacogenomics. We have a dual approach to questions of interest, on the one hand using laboratory-based experimentation with cell lines and other model systems, and on the other using DNA samples collected in clinical trials and other studies. We can complement and extend findings from the laboratory based studies by genetic analysis in our study cohorts, thus providing an immediate test of predictions and hypotheses evolving in the laboartory.

Some of our current projects are as follows:

Genetics and pharmacogenetics of depression.

This project examines genetic susceptibility factors that contribute to onset of mood disorders such as depression and bipolar disorder. Much of our work involves analysis of candidate genes by mutation analysis, and where possible functional analysis, in parallel with genetic analysis of patients recruited into research studies for these disorders. By exploring natural genetic variants (polymorphisms) that may contribute to these illnesses, we hope to better understand the biological underpinnings of these conditions. In addition, we seek to understand how genetic differences can lead to different responses to treatment, an area of research called “pharmacogenetics”. These combined approaches may offer insights into improved prevention, treatment and management of these common and disabling mental disorders. Most of our psychiatric genetics work is carried out in collaboration with Professor Peter Joyce, and A/Prof Kennedy is a co-PI on Prof Joyce’s HRC Programme Grant (Mental Health Clinical Research). Pharmacogenomics of antidepressants.

We are exploring how antidepressant drugs alter the expression of genes, with the goal of better understanding the mechanisms of actions of these drugs, and perhaps better understanding the molecular biology of mood. For this work, we use neuronal cell cultures, expression microarray analysis, qPCR and reporter gene analyses. Pharmacogenomics of thiopurine drugs.

Thiopurine drugs are effective therapies for treating a wide range of conditions including inflammatory bowel disease, leukaemia, dermatological disorders, organ transplants and several other diseases. However, around 40% of patients fail to respond, experience side effects or are intolerant to these drugs. Genetic variability may account for such varied responses between individual patients. This project is examining genetic variability in enzymes that metabolise or interact with thiopurine drugs, with a focus on inflammatory bowel disease patients. Using this approach we have already identified several novel mechanisms of drug intolerance or adverse responses. Identification of these and other such pharmacogenetic variants will allow improved prediction of adverse effects or drug intolerance, with consequent safer and more effective prescription of these drugs. This work is a collaboration with Dr Rebecca Roberts (Autoimmune Disease Research Group), Dr Richard Gearry and A/Prof Murray Barclay (Dept of Medicine). Gene x environment interactions in health and development.

In collaboration with Prof. David Fergusson and John Horwood, we are exploring the interaction of genetic and environmental factors in human health and development. This project is centred on the Christchurch Health and Development Study [1], a thirty-year longitudinal study of >1000 Christchurch babies born in 1977.

Other pharmacogenetics projects.

We are engaged in a range of other pharmacogenetics projects, with more details available here [2].