Eric W. Hewitt

I am a molecular cell biologist who is interested in how cells function in health and disease. I also have a long-standing interest in immunology. I obtained my PhD at the University of Manchester, where I studied protein translocation into the endoplasmic reticulum. Following this I was a postdoctoral fellow at the University of Dundee, the MRC Laboratory of Molecular Cell Biology and the University of Cambridge. In my postdoctoral research I studied antigen presentation by MHC molecules, protein trafficking pathways in specialised cells, protein degradation by lysosomes and how viruses can manipulate protein trafficking pathways in order to escape detection by the immune system. In 2002 I was appointed as Lecturer at the University of Leeds and I was promoted to a Senior Lecturer in 2011. I am also a member of the Astbury Centre for Structural Molecular Biology. My laboratory's principal research focus is on the cell biology and immunology of amyloid disease. Our goal is to determine how the structure and physical properties of amyloid fibrils and their oligomeric assembly intermediates affects cellular function and immune responses. This involves a multidisciplinary approach in which information obtained using structural biology techniques by colleagues in the Astbury Centre is integrated with analyses in my laboratory of cell function and viability. We are currently studying the oligomeric assembly intermediates, fibrils and fibril-derived oligomers formed by an array of amyloidogenic precursors, including α-synuclein (Parkinson’s), amyloid-β (Alzheimer’s) and β2-microglobulin (dialysis related amyloidosis). Experimental approaches used to analyse the interactions and effects of these amyloid species on cells include assays for cell viability and metabolism, live cell fluorscence microscopy, flow cytometry, subcellular fractionation and proteomics. In addition, we are exploring approaches for the delivery of amyloid aggregates into the cytoplasm of single cells with colleagues in the School of Electrical and Electronic Engineering. Key findings from my laboratory include the demonstration that amyloid fibrils are resistant to degradation by macrophages, nanoscale amyloid fibrils are more toxic than micron-length fibrils, lysosomes are a target for amyloid toxicity and that fibril-derived oligomers are toxic.