Molecular Cancer Epidemiology Group We and our Endometrial Cancer Association Consortium (ECAC) collaborators have identified common genetic variation at 20 genomic regions that associate with endometrial cancer risk. Although we have identified potentially causal risk variants, at most regions we do not know which genes these variants target. However, at two regions we have used… READ MORE
Molecular Cancer Epidemiology Group There is promising evidence that genetic studies of cancer will advance the development of new therapies. For example, clinically approved drugs are more likely to target proteins that have been linked to disease traits through genome-wide association studies (GWAS) than proteins with no such links. Indeed, several drugs already used to… READ MORE
Molecular Cancer Epidemiology Laboratory Panel gene testing is increasingly applied to identify the underlying genetic cause of cancer in patients with suspected hereditary cancer. Identification of a pathogenic variant directly influences clinical management for patients and their at-risk relatives, setting the path for preventative and increasingly chemotherapeutic options. Unfortunately such testing often identifies variants with… READ MORE
Neutrophils are the most abundant immune cells in humans and are thought to promote tumour progression and therapy resistance. However, the underlying cellular and molecular mechanisms are incompletely understood. We have recently, identified a novel target to inhibit neutrophil migration into tumours and the tumour draining lymph node, thus improving cancer immunotherapy. We have unravelled… READ MORE
Our studies have identified the involvement of Bruton’s tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) in both skin and lung GVHD, and demonstrated that treatment with Ibrutinib, an FDA-approved irreversible inhibitor of BTK and ITK, delayed progression, improved survival, and ameliorated clinical and pathological manifestations of cGVHD.(5) Although BTK inhibition has been… READ MORE
We have identified CSF-1 and Th17/Tc17 derived IL-17 as key cytokines that promote sequestration and differentiaton of fibrogenic tissue macrophages, and the critical role of Ly6Clo monocyte derived macrophages, in driving cGVHD pathology. Although each represents a targetable entity, IL-17, CSF-1, TGFb and macrophages themselves all play important roles in homeostatic processes including mucosal immunity… READ MORE
The role of autophagy dependent regulatory T cells in the control of chronic graft versus host disease
In contrast to aGVHD, where increased understanding of its pathophysiology has led to improved immunomodulatory chemotherapy and cellular therapeutics, the pathophysiology of cGVHD remains poorly defined. The majority of SCT recipients (70 %) now develop cGVHD which represents the major cause of late non-relapse death following SCT. Unfortunately, there is currently no satisfactory therapy for… READ MORE
Large overlap between mental health disorders is observed. For example, a patient diagnosed with autism is more likely to develop schizophrenia, and those who suffer from depression have a higher chance of developing alcohol dependence. Genetic factors may contribute to the observed overlap. The study aims to: describe patterns of overlap between mental health disorders… READ MORE
What makes one at risk for having a mental health disorder? Investigating the regulatory role of genetic variants
The risk of developing a mental health disorder, such as schizophrenia, depression, autism, or drug/alcohol addiction is to a large extent influenced by genetic factors. More effective interventions could be developed if we understood the biological mechanisms of a disease. Large-scale genetic studies have revealed regions in DNA that contribute to disease risk, but the… READ MORE
Using Parasite mRNA-sequencing and mathematical modelling to study how Plasmodium responds to the host in vivo
In collaboration with mathematical modeller, Professor Miles P. Davenport (UNSW, Sydney), we will use experimental models of malaria to examine an exciting new mechanism by which the host appears to control Plasmodium parasite numbers in vivo. We will use parasite RNA-seq and mathematical models developed by Prof Davenport to determine the molecular basis of this new phenomenon.
Using single-cell transcriptomics to study T cell responses in the gut during Graft-versus Host Disease
In collaboration with Dr. Motoko Koyama, we are interested in how CD4+ T-cells in the gut differentiate into an array of different effector states (Th1/Th17/iTreg) during Graft-versus-host-Disease, a common and severe complication following allogeneic stem cell transplantation. Using scRNA-seq and TCR transgenic CD4+ T cells we will explore how this process occurs in vivo.