Clare Louise Hawkins

Short presentation

Clare Hawkins joined the Department of Biomedical Sciences 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. She is a former Australian Research Council Future Fellow, and Principal Research Fellow within Sydney Medical School, University of Sydney, and has held other prestigious Research Fellowships including an R.D. Wright Career Development Fellowship from the National Health and Medical Research Council of Australia and a Career Development Award from the Australian National Heart Foundation. Clare has published 4 book chapters and > 80 peer-reviewed journal articles, including > 10 invited review articles. She has h-indexes of 35 (ISI Web of Science) and 40 (from Google Scholar), with her work averaging > 45 citations per paper. Her research is focused on understanding the role of oxidative stress and inflammation in driving lesion development in atherosclerosis.

Primary fields of research

Chronic inflammation is the major driving force of the disease atherosclerosis, which is characterised by the accumulation of lipid in infiltrating macrophages in the artery wall. The disease progresses over decades to form complex fatty lesions that lead to the clinical manifestations of myocardial infarction and stroke. The over-production of various chemical oxidants during inflammation and the resulting oxidative stress play a key role in lesion development. Our research is focused on understanding how oxidants produced during inflammation modify the structure and function of biological molecules and cells associated with the arterial wall, as a means to develop more targeted therapies to prevent lesion formation and slow the progression of atherosclerosis.

Current research

We are particularly interested in oxidants produced by an enzyme called myeloperoxidase, which is produced in the arteries by infiltrating immune cells during inflammation. Myeloperoxidase is both a risk factor for coronary artery disease and a prognostic agent for patient outcome following cardiac complications, and is strongly associated with the development of atherosclerosis. The major oxidant produced by myeloperoxidase is a chemical called hypochlorous acid (HOCl, bleach), which kills bacteria and invading pathogens in our immune system. However, this oxidant is also formed in elevated amounts in the arteries during chronic inflammation, and is strongly implicated in causing cellular damage and accelerating disease. Our projects focus on gaining an understanding of the fundamental biochemical pathways responsible for vascular cell dysfunction in atherosclerosis and other inflammatory diseases, using a range of analytical (e.g. EPR spectroscopy, HPLC, LC-MS/MS, Seahorse analyser) and molecular biology (e.g. ELISA, qRT-PCR, SDS-PAGE, flow cytometry) methodologies.

Projects

1. Investigating the molecular mechanisms involved in vascular cell damage and death
There is epidemiological, clinical, and experimental evidence that cellular stress and excessive inflammation are causally linked to various pathological conditions including atherosclerosis. One of the hallmarks of atherosclerosis is the infiltration of macrophages within the vascular wall at sites of inflammation, contributing to atherosclerotic lesion formation. Excessive oxidant formation within this environment, generated as part of the inflammatory response to injury, results in oxidative stress, damage and ultimately death to all cells of the vasculature. We are investigating how inflammatory oxidants modulate the cellular redox environment and cause changes in gene expression, to contribute to the development of disease. 

2. Cellular mechanisms linking smoking and cardiovascular disease
Atherosclerosis is four times more prevalent in people who smoke, resulting in far more deaths from coronary heart disease in smokers than non-smokers. Although it is well established that smoking independently increases the risk of dying from cardiovascular disease, the mechanisms responsible for this elevated risk are not well understood. Smokers have elevated plasma levels of thiocyanate and hence produce greater amounts of the myeloperoxidase-derived oxidant hypothiocyanous acid (HOSCN). The selectivity and reactivity of this oxidant is markedly different to the chlorinating myeloperoxidase oxidant hypochlorous acid (HOCl). We are examining the role of HOSCN to modulate vascular cell function and investigating novel, targeted, antioxidant therapies to prevent or modulate this process.

3. Extracellular Traps and DNA Damage – key players in atherosclerosis?
Neutrophils (a type of white blood cell) release extracellular traps, termed “NETs”, following a novel mode of cell death called NETosis. These structures trap and kill bacteria, and consist of a mesh of DNA and histones decorated with neutrophil proteins including myeloperoxidase, which produces oxidants. In addition to the well-defined role of NETs in innate immunity, there is growing evidence for a key role of NETs and extracellular traps from other immune cells in disease, particularly those involving inflammation. We are studying the pathways involved in extracellular trap release from immune cells, and how modification of the building blocks of RNA and DNA influences cellular function.

CV

Education
BSc(Hons) Chemistry, University of York, UK (1993)
PhD Chemistry, University of York, UK (1997)

Previous Positions
2015 – 2016 Scientific Director, Heart Research Institute, Sydney
2007 – 2016 Group Leader, Inflammation Group, Heart Research Institute, Sydney
2011 – 2016 Principal Research Fellow, Sydney Medical School, University of Sydney
2014 – 2015 Acting Scientific Director, Heart Research Institute, Sydney
2000 – 2007 Senior Research Fellow, Free Radical Group, Heart Research Institute, Sydney
2004 – 2010 Senior Research Fellow, Faculty of Medicine, University of Sydney
2001 – 2004 Honorary Academic Research Fellow, Faculty of Medicine, University of Sydney
1997 – 2000 Postdoctoral Research Officer, Free Radical Group, Heart Research Institute, Sydney

Professional Experience

Postgraduate Research Coordination
2009 – 2015 Sub-Dean for Postgraduate Research, Sydney Medical School, University of Sydney
2012 – 2016 Deputy Associate Dean (Postgraduate Research) / Deputy Chair, Research Sub-Committee of the Combined Board of Postgraduate Studies (Dentistry, Medicine and Pharmacy), University of Sydney

Scientific Societies 
2013-2014 President of the Society for Free Radical Research (Australasia)
2010-2012 President-Elect of the Society for Free Radical Research (Australasia)
2004 – 2007 Secretary of the Society for Free Radical Research (Australasia)

Editorial Board Positions
Associate Editor, Biochemistry Society Transactions
Editorial Boards of Archives of Biochemistry and Biophysics, Biochemical Journal, Redox Report

Scientific Peer-Review Committees
2013-2015 Chair NHMRC Biomedical Early Career Fellowship Peer-review Panel
2013  National Heart Foundation (NHF) Collaboration and Exchange Award Panel
2012  Grant Review Panel (Cardiovascular Disease and Nephrology) NHMRC
2012  Vice-Chair of the NHF Biomedical Scholarships Committee
2009 - 2011 National Heart Foundation Travel Award Committee
2005 – 2011 NHMRC Training Awards Committee (Panel Chair in 2006 – 2008)

Organisation of Scientific Meetings (last 5 years)

• Scientific Advisory Committee, 10th International Human Peroxidase Meeting, Denver, Colorado, USA, August 2017.
• Program Committee for the Society for Redox Biology and Medicine (SfRBM) 24th Annual Meeting, Baltimore, MD, USA, November 2017.
• Symposium Co-Chair “Dual role of oxidants generated by leukocyte enzymes in health and disease”, 18th Biennial Meeting of the International Society for Free Radical Research, San Francisco, USA, November 2016.
• Member of the Scientific Advisory Panel, for the Annual Meeting of the Australian Vascular Biology Society, Kiama, NSW, Australia, November 2015. 
• International Scientific Programme Committee for the Joint Meeting of the Society for Free Radical Research (Europe) and Society of Nutrition and Food Science, Germany, September 2015. 
• Symposium Organiser and Co-Chair “Oxidation of DNA/RNA and signalling by poly (ADP-ribosyl)ation”, 17th Biennial Meeting of the International Society for Free Radical Research, Kyoto, Japan, March 2014.
• Organising Committee for the 8th International Human Peroxidase Meeting, Sydney, September 2013.
• Organising Committee for the 6th Joint Meeting of the Societies for Free Radical Research Australasia and Japan, Sydney, September 2013.