Mammalian Heme Peroxidases

Clare Hawkins is a Professor in the Department of Biomedical Sciences, University of Copenhagen. She appointed in March 2017 after nearly 20 years in Sydney at the Heart Research Institute, where she held the position of Scientific Director and the Inflammation Group Leader. Clare is a former Australian Research Council Future Fellow, and Principal Research Fellow within Sydney Medical School, University of Sydney. She completed her PhD in Chemistry at the University of York (UK) before making the move to Sydney where she eventually became Head of the Inflammation Group at the Heart Research Institute. Her research is focused on understanding how chemical oxidants modulate cellular function under inflammatory conditions, and the role of these reactions in the pathogenesis of inflammatory diseases, including atherosclerosis. Prof Hawkins has been awarded prestigious Career Development Awards including a R. Douglas Wright Biomedical Fellowship from the National Health and Medical Research Council (NHMRC) of Australia in 2003, a Career Development Fellowship from the National Heart Foundation of Australia (NHF), and an Australian Research Council (ARC) Future Fellowship, together with project grants from both European and Australian funding agencies. She has authored several book chapters and about 100 peer-reviewed journal articles in high-quality, journals, attracting more than 5000 citations.William M. Nauseef is a professor in the Department of Microbiology at the University of Iowa. He also serves as the Director of the Inflammation Program, also at the University of Iowa. He received his MD from the SUNY Upstate Medical Center, Syracuse, New York. He is Board Certified by the American Board of Internal Medicine in Infectious Diseases. He is the author or co-author of over 180 peer reviewed papers, has co-authored 2 books, and co-authored dozens of book chapters. His research program over the past ~ four decades has focused on elucidating the cell and molecular biology of human neutrophils within the context of innate host defense against infection.

• SECTION 1: INTRODUCTION TO MAMMALIAN HEME PEROXIDASES Structure, function, phylogeny of heme peroxidases Biosynthesis of MPO and other heme peroxidases Peroxidasin structure and function SECTION 2: REACTIVITY OF PEROXIDASE OXIDANTS Reactivity of peroxidase oxidants with proteins and proteoglycans Reactivity of peroxidase with nucleic acids, RNA and DNA Reactivity of peroxidase oxidants with lipids – modification and signaling Role of MPO in the modification of lipoproteins (LDL and HDL) Regulation of cellular signaling and survival by peroxidase oxidants Global profiling of cell responses to peroxidase oxidants SECTION 3: PEROXIDASES IN INNATE IMMUNITY MPO and immune cell recruitment and activation Role of MPO in extracellular trap release by neutrophils Imaging HOCl production by neutrophils How microbes combat reactive chlorine species Priming the innate immune system to combat respiratory disease SECTION 4: PEROXIDASES IN PATHOLOGY Imaging the reactivity of MPO in vivo Role of MPO in vascular dysfunction and signaling MPO in ischemic heart disease Role of MPO in neurodegenerative disease Role of MPO in kidney disease Role of peroxidases in respiratory disease Role of peroxidasins in disease SECTION 5: PREVENTION OF MPO INDUCED DAMAGE Design and functionality of MPO inhibitors Modulation of disease using MPO inhibitors Novel peroxidase inhibitory protein “SPIN” with broad target specificity Selenium and resistance to oxidative enzyme inactivation

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