Research
Our lab research explores the molecular architecture of complex disorders at the individual and population level to better understand their treatable components in order to provide targeted therapy.
Most common health problems, and the distress, disability, and death associated with them, don’t have a single cause. These are known as complex disorders and include heart disease, inflammatory conditions, neurological disorders, psychiatric disorders and cancer. Their onset involves multiple risk factors that can vary dramatically from individual to individual, making accurate and effective treatment difficult. In each case the underlying biology and response to treatment can be quite different such that current therapies for these disorders are not targeted to all the relevant causal factors. Unfortunately, this often results in unsatisfactory outcomes, including the persistence of disease or unwanted side effects.
Our research also aims to identify the modifiable components of disease risk in individuals prior to disease onset to inform preventative health strategies that can potentially reduce the need for treatment altogether.
Below we describe some of our main research themes with links to papers.
Precision tools for drug repurposing
Our lab has recently developed a precision medicine tool for identifying drug repurposing targets for difficult to treat disorders. We call this tool Pharmagenic Enrichment Score or PES for short. PES is described in a number of recent publications including a nature reviews genetics article, and in greater detail here. This polygenic scoring approach enables the quantification and stratification of genomic risk in pharmacologically sensitive pathways, which could be used as a companion diagnostic to specifically match an individual’s genetic profile for complex disorders with the most appropriate treatment. A number of intriguing results have come from applying PES to complex disorders such as schizophrenia, lung function and pneumonia.
Several translational genomics projects are now underway to apply PES to other disorders for drug discovery and exploration of the systems biology of complex diseases.
Population genetics of complex disease
Our lab group has a number of ongoing and completed projects making use of big data and advanced statistical tools to explore medical disorders with complex genetic and environmental causes. Historically, this work has focused on neuropsychiatric disorders, but we are expanding this work into a broader set of complex disorders and traits including cancers and diabetes.
Some examples of what we have done include work led by Danielle Adams which has explored links between glycaemic traits and psychiatric disorders using Mendelian randomisation. We have utilised population genetics and bioinformatics to extract more biological insight from large data sets , for example gene level cross disorder analysis between schizophrenia and other psychiatric disorder, led by William Reay and between schizophrenia and substance use disorders. We have also contributed to the ENIGMA Consortium to determine the common variant contribution to the structure of the human cerebral cortex published in Science. This work was followed up Dylan Kiltschewskij, which identified a link between C-reactive protein and structure of the human cerebral cortex.
This research theme has included our involvement with the establishment and analysis of the Australian Schizophrenia Research Bank. We also continue to participate in a number of international collaborations which have yielded landmark publications including the Psychiatric Genomics Consortium’s schizophrenia GWAS which utilised data from the ASRB.
Neuropsychiatric medicine
We also continue to explore the molecular mechanisms for psychiatric and complex diseases through carefully designed laboratory experiments. Recent publications from this theme include work lead by Behnaz Khavari on the effect of reactive oxygen species on the transcriptome of differentiating neurons. And a number of projects lead by Michelle Barnett and Dylan Kiltschweskij on schizophrenia related miRNAs and transcriptomic and translational analysis of whole cell depolarization of differentiated neuroblast cultures.
Methodology
Our research group utilises a diverse set of techniques both in the wetlab and computational. If you are interested in these, our lab might be a good fit for you! A non-exhaustive list of these is included below:
Cell biology
Animal models, molecular cloning, PCR, qPCR, small RNA synthesis, DNA/RNA gel electrophoresis, bacterial and eukaryotic cell culture
Statistical genomics
GWAS, METAL, MAGMA, PGS, TWAS, LCV, MR
Systems biology
MAGMA, SEQ-GSEA, GO ontology enrichment tools
Programming/Scripting languages
R, python, SQL, Javascript
Machine learning
SVM, RF, BSNA
Functional genomics
DNA Sequencing, Transcriptomics, siRNA, CRISPR, Methylomics
Contact
The University of Newcastle acknowledges the traditional custodians of the lands within our footprint areas: Awabakal, Darkinjung, Biripai, Worimi, Wonnarua, and Eora Nations. We also pay respect to the wisdom of our Elders past and present.