Research overview

Cancer is one of the biggest causes of death in the Western world. Our group develops new approaches to study signalling networks in cancer cells and to uncover specific weaknesses, particularly in breast and lung cancer, that can be used for developing more effective targeted drugs and for guiding treatment decisions. We develop and employ high-throughput chemical and genetic screening approaches and haploid genetics to engineer isogenic human cancer cells and tease out drug-gene interactions that could be therapeutically exploited. These interactions are then studied in more detail using cell culture, mouse models, and patient samples.

Human cancers are genetically highly diverse and every tumor displays a unique mutation landscape. This genetic diversity underlies much of the variability in therapeutic response that is observed in patients. Indeed, many cancer drugs currently used in the clinic only work on a limited number of patients. To unravel the complex interplay between genetics and drug action, our group is engineering isogenic cancer cells with controlled genetic mutations. We have used this approach to identify drugs targeting unanticipated weaknesses in triple negative breast cancer and lung cancer, as well as pinpointing mechanisms of drug resistance. We are currently investigating the clinical relevance of these findings and studying the molecular mechanisms underlying these gene-drug interactions. Our approach is also easily expanded to almost any other cancer type.

We are also developing haploid genetics approaches, which involve a human cell line that contain only one copy of each of the 23 chromosomes. These cells are a valuable new tool for studying many different cell biological processes including cancer and mechanisms of drug action. Several projects in the lab are employing haploid genetics to construct gene-gene and gene-drug interaction networks. These studies will contribute to a better understanding of the cellular wiring of human (cancer) cells and the mechanism of action of drugs.