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The origin and consequences of epigenetic alterations in cancer metastasis

The aim of this theme is to identify progressive epigenetic changes responsible for or involved in cancer metastasis. There is substantial interest in developing methylation-based biomarkers (as these are DNA based, they are stable and easily measurable). Further, unlike genetic changes, epigenetic changes are reversible and the growing efforts to develop combinatorial therapies (e.g. immunotherapy with epigenetic therapies) are already showing promising results. Improved understanding of functional epigenetic changes would significantly contribute to develop early cancer detection strategies and new epigenetic therapies to enhance patient outcomes.

Developing analytical tools for epigenomic analysis

Dr Chatterjee has played a lead role in establishing RRBS, being the first researcher to establish DMAP package sequencing-based DNA methylation analysis technique in Australasia, including the development of a pipeline for robust analysis of DNA methylation patterns in eukaryotic genomes. The pipeline is currently one of the fastest available for large-scale methylation analysis, and Dr Chatterjee has invested much time and effort into streamlining the RRBS technique. Further, Chatterjee Lab members developed the scan_tcga tool suite to retrieve and analyse TCGA data by specific patient subgroup.

Our groups work closely with local bioinformaticians for developing new analysis pipelines and streamlining existing strategies for epigenetic analysis. The Chatterjee Lab will continue to develop tools and statistical methods for accurate analysis of epigenomic datasets from next generation sequencing technologies (NGS).

Cellular and tissue specific epigenetics

We performed the first genome-wide study to provide single-nucleotide resolution DNA methylation profiles in human neutrophils and showed existence of widespread inter-individual variation in epigenetic marks in a normal population. This work provides a comprehensive resource for understanding the nature and mechanism of variable phenotypic traits and altered disease susceptibility due to variable DNA methylation patterns, and also has broader implications for the selection of DNA methylation based biomarkers.

We study the relationship and implications of inter-individual and tissue-specific methylation variations in humans. The Chatterjee Lab is also involved in performing an epigenome-wide association study (EWAS) on different blood cell populations in collaboration with the Jones Lab, Department of Surgical Sciences, University of Otago.

Environmental epigenetics

The Chatterjee Lab published the first single-nucleotide resolution DNA methylation map of adult male and female zebrafish brain and liver tissues. This work provided the epigenetic landscape of zebrafish and opened new avenues for using this model to further understand the biology of DNA methylation (such as sex determination mechanism in teleosts, effects of environmental pollutants in altered methylation, and phenotype).

Our group is involved in studying epigenetic and phenotypic effects of environmental pollutants in model organisms (zebrafish and clonal species mangrove rivulus). We collaborate with the Silvestre group in Belgium to study environmental epigenetics. Dr Chatterjee is also a visiting faculty member at the University of Namur in Belgium.

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