Our research aims to understand the epigenetic regulation of transposable elements and how their dysregulation contributes to the generation and development of cancer. In particular, we investigate their roles as gene regulators and triggers of anti-tumour immunity in blood cancers.
Our research aims to understand the epigenetic regulation of transposable elements and how their dysregulation contributes to the generation and development of blood cancers. In particular, we investigate their roles as gene regulators and triggers of anti-tumour immunity in blood cancers. Our long-term vision is to address how we can utilise transposable elements as a gateway to develop new and effective treatments for cancer.
Transposable elements (TEs) are mobile DNA segments that have expanded within the human genome throughout evolution. TEs have evolved cis-regulatory sequences to exploit the host cellular machinery to promote their own transcription and replication. Whilst the vast majority of TEs in the human genome have been rendered immobile due to mutation, many have retained their regulatory function. Given their selfish nature, TEs have dispersed vast amounts of cis-regulatory sequences and transcriptional units across the genome, providing an abundant source of transcriptional modulatory elements.
Epigenetic dysregulations are hallmarks of cancer and that provides a particularly fertile ground for TE activation. In fact, we revealed the first examples of TEs activated as oncogenic enhancers in acute myeloid leukaemia (AML), which conferred a proliferative advantage to the cells (Deniz et al, Nat. Comms., 2020). In contrast, genome-wide epigenetic changes in cancer cells could also potentially activate TEs that regulate the expression of tumour suppressor genes, leading to loss of cancer cell fitness; or trigger anti-tumour immune responses leading to the destruction of cancer cells via “viral mimicry”.
Using AML as a model system, the overarching goal of the Deniz Lab is to comprehensively delineate the molecular and cellular functions of TEs in the cancer genome and characterise the epigenetic mechanisms that define their diverse activities. To achieve this aim, we will:
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