We are interested in dissecting the cell stress response and its regulation by signalling networks. Our strategy is to use molecular cell biology and genetics to probe sets of pathways and critical regulatory factors, both to understand normal biology and to highlight potential sensitive nodes to prioritise as new drug targets.
Our long-standing focus has been to understand the role and regulation of the autophagy cell homeostasis pathway. By directing different cytoplasmic cargo to the lysosome, autophagy plays an essential degradative role that helps maintain metabolism and cellular quality control, thus outlining two of its critical pro-survival functions. As such, better understanding of autophagy mechanisms will provides strategies on how to improve overall cell health, reduce cellular damage and, in turn, slow cellular ageing.
I obtained my Ph.D. at the University of Alberta, Canada, studying the RAS-MAPK signalling and cellular transformation using cDNA library and mutagenesis screens. This work helped identify a novel RAS guanine nucleotide exchange factor, a novel hypothermia-driven mode of RAS activation and oncogenic regulation the kinase cRAF1. I carried out postdoctoral work in Medical Genetics, University of British Columbia, Canada, studying new therapies for Huntington disease. Our approach was to dissect molecular mechanisms by gene expression profiling in different mouse models. My work on Huntington disease led me to study the function of Huntington-associated protein 1 (HAP1) which also regulated endocytic trafficking. I gained further training in membrane cell biology at Cancer Research UK London Research Institute, leading to my interest in autophagy. In these initial studies, I discovered ULK proteins using siRNA screens for regulatory factors. We have been further investigating the signalling mechanisms linking ULK1 to autophagy, which has expanded into the several streams underlying my current research.