Ï㽶ÊÓƵ

My research interests focus around the molecular pathways leading to Alzheimer’s disease. Mutations in the amyloid precursor protein (APP) causatively link APP to Alzheimer’s disease, however, its physiological function is still incompletely understood. APP is cleaved by several proteases and we have identified a new, additional protease cleaving APP, i.e. the rhomboid-related protein 4 (RHBDL4). RHBDL4’s activity is regulated by cellular cholesterol levels, potentially linking this pathway to cholesterol as an established risk factor for Alzheimer’s disease. Furthermore, the cholesterol transporter apolipoprotein E variant 4 (ApoE4) is genetically causatively linked to Alzheimer’s disease, again an incompletely understood molecular pathway. My goals are to: 1) fully reveal the physiological function of APP utilizing the RHBDL4-mediated processing pathway, and 2) to understand cellular cholesterol distribution in the brain in relation to ApoE4 and other cholesterol-transporting proteins. My team utilizes appropriate cell culture and mouse models and a wide range of core facility tools available at McGill including mass spectrometry, fluorescent and electron microscopy, histology, FACS, the transgenic animal core, PET imaging and metabolomics. Our gained knowledge will inform us to develop new therapeutic strategies to prevent the onset of Alzheimer’s disease.