We are interested in the application of genetics to the understanding and treatment of disease. Our main research themes are pharmacogenomics, psychiatric genetics, and the genetics of complex disease. Our laboratory is a key part of the Carney Centre for 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 laboratory.
Pharmacogenomics of drug responses and adverse drug reactions
Genetic differences between people can impact on their responses to therapeutic drugs. We are exploring genes which may contribute to such variation in outcomes of drug treatment. Depending on the nature of the drug response or reaction, we will either home in on specific genes that control metabolism of drugs, or apply more advanced and comprehensive genomic methods, to identify potential genetic differences that may explain these differences in the outcomes of drug treatment. This work is part of a research study called UDRUGS (Understanding Drug Reactions and Unusual Responses by Genome Sequencing), that involves patients with various serious adverse drug reactions or unusual drug responses, for a range drugs.
Pharmacogenomics of mood disorders
We are examining the effects of drugs used for treatment of mood disorders, such as valproate acid or lithium, on patterns of gene expression. Much of this work is being carried out in the serotonergic cell line RN46A. Genes that are regulated by these drugs may be important in therapeutic responses, and looking at patterns of gene expression change may provide insights into the mechanisms of action of these drugs.
Gene x environment interactions in health and development
Professor Martin Kennedy is a co-investigator with Associate Professors John Horwood and Joseph Boden on an HRC programme grant centred on Christchurch Health and Development Study (CHDS), a forty year longitudinal study of >1000 Christchurch babies born in 1977. The focus of the Gene Structure and Function Lab involvement in this programme is analysis of gene by environment interactions, pathway analysis of genetic variants in various phenotypes, and analysis of structural variation and its relevance to personality and mental health.
As part of the Genes, Environment, Development Initiative (GEDI) funded by the National Institute on Drug Abuse (NIDA) USA, and in collaboration with Drs Jane Costello (Duke) and Patrick Sullivan (UNC), we have obtained gene chip (Illumina 660W Quad) SNP genotype data on 780 CHDS participants. These data are primarily being used to investigate genetic and environmental influences on addiction, but we are also interested in other collaborative studies that might make use of this body of data and the longitudinal information collected over 30 years for the CHDS.
G-quadruplex structures in DNA
We are exploring the role of unusual DNA structures called DNA quadruplexes, particularly with regard to the process of genomic imprinting. These structures form in single stranded DNA and RNA, and involve bonding between “G” bases in an unusual manner. It is clear that these structures form in DNA and RNA within cells, and they play many important functions, although much remains to be learnt about the full range of their roles in the cell. This work is supported by a grant from the Marsden Fund.
Anorexia Nervosa Genetics New Zealand
Professor Martin Kennedy and Dr Jenny Jordan (Department of Psychological Medicine, UOC) have contributed New Zealand samples to the Australasian arm of a large international study (ANGI) which seeks to understand genetic factors that predispose to the eating disorder Anorexia nervosa.