A description of our research for non-scientists can be found here.
The Faller lab is studying the role that RNA translation plays in models of cancer. In recent years it has become clear that cancer cells use multiple mechanisms to up-regulate oncogenes and down-regulate tumour suppressor genes. Much of the focus of this research has been on modulators of transcription; however we now estimate that transcriptional control only explains 30% to 40% of protein level variation. One of the major reasons for this discrepancy is thought to be differences in RNA translation.
Colorectal cancer (CRC) is the second most common cause of cancer mortality, with around 700,000 deaths annually. While this number has been steadily decreasing over the last 4 decades, this has largely been as a result of screening programs, and our treatment options have lagged behind.
Our lab uses mouse models of CRC to study the effect that changes in RNA translation have on this disease. We have previously shown that CRC cells require increased RNA translation in order to proliferate. We also showed that by blocking this RNA translation we could protect mice from the disease. Our aim is now to fully understand the role that RNA translation plays, in order to identify therapeutic targets and potentially develop drugs that can target this process.
We have also pinpointed the elongation phase of RNA translation as being a crucial level of regulation in CRC. Interestingly, this regulation via elongation is specific for a subset of pro-proliferative RNAs. We want to understand why certain genes are regulated in this manner and others not. If we can understand this mechanism it may provide us with a rationale for targeting abnormal elongation in cancer with chemotherapy. Alternatively, by understanding which particular genes are regulated like this, it may be possible to target them instead. For example, we have shown that Cyclin D3 is controlled by elongation, while other highly homologous family members (Cyclin D1 and Cyclin D2) are not. Given its role as a regulator of the cell cycle, we are now trying to elucidate the importance of Cyclin D3 in the context of cancer.
Our lab aims to combine the use of innovative technologies with state-of-the-art mouse models, in order to give us a much more thorough understanding of the role that RNA translation plays in cancer, while at the same time identifying many new, exciting therapeutic targets for the disease.