• The Altas of Variant Effects Alliance – As part of these studies we are developing high-throughput methods to systematically and comprehensively identify all pathogenic alleles of cancer-associated genes. We are using techniques such as saturation genome editing at scale.
• The Genomic Atlas of Dermatopathology – While the majority of cancer deaths are associated with melanoma, a malignancy of melanocytes, there are more than 300 other skin cancer types most of which have never undergone next-generation sequencing and thus we are unaware of the driver genes in these tumours or the exposures that might promote their development. The genomic atlas of dermatopathology brings together a group of world-leading pathologists to tackle this problem.
• Combinatorial CRISPR Screening – We have a long interest in understanding cancer pathways. As part of these studies we have developed CRISPR libraries that target pairs of genes at the same time so as to identify synthetic lethal interactions and also gene redundancy. We are using these libraries to systematically screen cancer cell lines with a particular focus on metastatic melanoma, lung and pancreas as these are cancers of unmet clinical need. We are also performing a “deep dive” into the biology of several candidates to understand the basic mechanisms by which synthetic lethal gene pairs function.

We have a broad interest in many aspects of cancer biology. Cancer occurs when there is an accumulation of genetic damage that confers a selective advantage on a cell, allowing it to evade normal growth control processes. Uncontrolled growth of these damaged cells ultimately results in tumour formation. While some of the key events at the molecular level that are involved in cancer formation are known, there is still much work to be done to identify those genetic changes that are important for cancer and that represent new diagnostic markers or therapeutic targets.