Vice Dean for Research and Innovation
Director of Dementia Research
Editor in Chief, Essays in Biochemistry
Medical Research Council Neurosciences and Mental Health Board (2000-2004)
MRC/Department of Health Research Advisory Group for Transmissible Spongiform Encephalopathies (2001-2004)
Government's Spongiform Encephalopathy Advisory Committee (SEAC) (2004-2009)
Scientific Advisory Board of Alzheimer's Research UK (2007-2014) including latterly as Chair of the Advisory Board (2012-2014).
Editorial board (1998-2002) and deputy chairman (2002-2009) of the Biochemical Journal.
Editorial board of the Journal of Biological Chemistry (2009-2014).
Nigel Hooper received his Ph.D. in biochemistry at the University of Leeds in 1987. He was then awarded a Mr and Mrs John Jaffé Donation Research Fellowship from the Royal Society to work on the proteolysis and membrane anchorage of mammalian cell surface peptidases. In 1989 he was appointed as lecturer in the Department of Biochemistry at Leeds, followed by promotions to senior lecturer, reader and in 2001 to Professor of Biochemistry. He served as Director of the Institute of Molecular and Cellular Biology (2007-2011), Pro-Dean for Research (2011) and Dean (2012-2014) of the Faculty of Biological Sciences at the University of Leeds. In 2014 he was appointed to the Chair in Cell Biology in the Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences at the University of Manchester. He is currently Vice Dean for Research and Innovation in the Faculty of Biology, Medicine and Health, and Director of Dementia Research for the University.
His research has focused on neurodegenerative and cardiovascular diseases. He applies a range of experimental approaches (biochemical, biophysical, molecular biological and cell biological techniques on individual proteins, cells in culture, animal models and human tissues) to probe normal biology and elucidate disease processes, with a common theme of proteolytic mechanisms and protein-membrane interactions, that began with angiotensin-converting enzyme (ACE) and has led naturally into studies on Alzheimer’s and prion diseases. He was the first to show how ACE attaches to the cell membrane, and to identify the mechanism whereby it is processed (shed) into a soluble circulating form through the action of another zinc metalloprotease. This model of ectodomain shedding has become the paradigm for numerous biologically and medically-important processes, including the cleavage of the Alzheimer’s amyloid precursor protein (APP). This work also led him to identify and extensively characterise the first known human ACE homologue, ACE2, and to delineate its role in angiotensin metabolism: discoveries that have made important contributions to understanding of cardiovascular and renal pathophysiology.
His work on the membrane attachment of ACE led him to be the first to show that multiple glycosyl-phosphatidylinositol (GPI)-anchored proteins are resistant to solubilisation from the membrane by certain detergents, subsequently shown to be due to localisation within cholesterol-rich membrane rafts. This work led him to develop a productive programme of research targeting the GPI-anchored prion protein (PrP). Significantly, he identified determinants in PrP for its raft association and glypican-1 as important in its conversion into the infectious form. He also showed that PrP is involved in zinc uptake into neurons, that disease-associated mutations inhibit this metal-uptake function, that metal binding promotes the movement of PrP out of rafts prior to clathrin-mediated endocytosis, and that proteolysis contributes to its shedding from the membrane. These studies have contributed to elucidation of the normal cell biology of PrP and provided insights into how loss of function (e.g. zinc uptake) contributes to its pathogenic role in prion disease.
Through manipulating its membrane anchor his group elegantly showed that the localisation in rafts of the β-secretase, BACE1, is a key factor regulating the production of the neurotoxic amyloid-β peptide in Alzheimer’s disease. More recently he was the first to report a molecular link between PrP and Alzheimer’s disease, when he showed that PrP inhibits the β-secretase-mediated cleavage of APP and thus amyloid-β production. He has also shown that PrP must be localized in rafts in order to mediate amyloid-β binding and subsequent toxic intracellular signalling, opening up potential new avenues for therapeutic intervention in Alzheimer’s disease.
B.Sc. (Hons.) Biochemistry, University of Leeds 1984
Ph.D. Biochemistry, University of Leeds 1987
Fellow of the Royal Society of Biology 2016
Member of Academia Europaea 2017