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Kemp-Harper and Broughton Lab research

Our research | CollaborationsStudent research projects | Publications

About Associate Professor Barbara Kemp-Harper

Associate Professor Barbara Kemp-Harper co-leads the Cardiovascular and Pulmonary Pharmacology Group and has an established international reputation in the field of vascular pharmacology. Her research aims to identify novel strategies for the prevention and treatment of vascular disease (systemic & pulmonary) with a focus on the NO/cGMP signalling pathway and inflammation.

Associate Professor Barbara Kemp-Harper obtained her PhD in 1995 under the supervision of Dr Tom Cocks and Dr Joe Smolich at the Baker Institute and the Department of Pharmacology, University of Melbourne. Her studies focused on the role of the endothelium in the control of pulmonary vascular function. In 1998 she was awarded an NHMRC CJ Martin Fellowship to conduct postdoctoral studies at the Wolfson Institute for Biomedical Research, London with Professor Salvador Moncada. Here she pursued her interests in nitric oxide signalling and studied its ability to regulate mitochondrial respiration.

In 2000 she returned to the Department of Pharmacology at Monash University where she established her own Vascular Pharmacology Group. In 2001 she instigated a research program examining the vasoprotective actions of nitroxyl, a novel redox sibling of nitric oxide. In 2008 she was awarded a Foundation for High Blood Pressure Research Postdoctoral Fellowship and she and her research team joined the Vascular Biology and Immunopharmacology Group, co-led by Chris Sobey and Grant Drummond. In 2017, she established the Cardiovascular and Pulmonary Pharmacology Group with Dr Brad Broughton.

Associate Professor Kemp-Harper has been a Chief Investigator on three NHMRC Project Grants, an ASCEPT Councillor and is currently an Editor for the British Journal of Pharmacology. She has received numerous speaking invitations to international and national conferences and has many productive collaborations with colleagues both within Australia and overseas (see News for awards and prizes).

Associate Professor Kemp-Harper has a long-standing interest in the mechanisms underlying blood vessel dysfunction in cardiovascular disease. She is internationally recognised for her work on nitroxyl, a novel sibling of nitric oxide, which has many advantages over nitric oxide. Barbara's work has identified a potential for nitroxyl-like drugs to be used in the treatment of angina, high blood pressure and high cholesterol. Her recent research program focuses on the role of the innate immune system in the pathophysiology of systemic and pulmonary hypertension, exploring the therapeutic utility of targeting the chemokine, CCL18 and NLRP3 inflammasome-derived cytokines in the treatment of these diseases.

About Dr Bradley Broughton

Dr Brad Broughton is a senior lecturer and co-leads the Cardiovascular and Pulmonary Pharmacology Group. Brad's research has contributed to our knowledge of reactive oxygen species, calcium, apoptosis, oestrogen, Rho kinase and nitric oxide signalling in the systemic, pulmonary and cerebral circulations. His studies have elucidated physiological mechanisms in vivo and in vitro, identified gender differences, as well as abnormalities in diseases, particularly in stroke and pulmonary hypertension. The primary focus of his current research is to advance our understanding of mechanisms that contribute to brain damage after stroke and develop safe and effective pharmacological and cell-based therapies. In 2018 he published a senior author study that found intravenous post-stroke injection of hAECs can markedly improve outcomes in both rodent and non-human primate models of cerebral ischemia; published in Stroke. Excitingly, this work has resulted in a Monash-led clinical trial to evaluate the therapeutic potential of hAECs in stroke patients.

Dr Brad Broughton completed his PhD in 2005 in the School of Biological and Chemical Sciences at Deakin University. He then moved to the University of New Mexico in the United States where he was an American Heart Foundation Postdoctoral Fellow and his research investigated calcium signalling mechanisms associated with chronic hypoxia induced-pulmonary hypertension. In 2008, he returned to Australia and joined the Department of Pharmacology at Monash University. Since then Dr Broughton has attracted nationally competitive funding (NHMRC Development Grant & Project Grant, NHF Grant in Aid, NHF Postdoctoral Fellowship, CASS Foundation grants (2x) and a Foundation for High Blood Pressure Research Postdoctoral Fellowship) as well as being awarded several Interdisciplinary Research Grants from Monash University. In addition, between 2009-10 he was co-project leader of a major stream as part of a Cooperative Research Centre funded project (Biomedical Imaging Development). Brad has also received numerous national speaker invitations and prizes. (See News for awards and prizes). He currently is an Executive Committee member of the High Blood Pressure Research Council of Australia and has served as an NHMRC chair/panel member for PhD/ECR Fellowships for the past 6 years.


Our research

Current projects

1. Targeting the CCL18-CCR8 axis to treat hypertension-associated end organ damage (Systemic hypertension)

Hypertension is a major cause of heart failure, heart attacks and strokes. Associated with the development of hypertension is the accumulation of macrophages in the arterial wall leading to fibrosis and vascular stiffening of central elastic arteries (i.e. aorta, carotid artery). This results in a reduced capacity of these vessels to buffer pulse pressure leading to peripheral vascular and end-organ damage. Whilst current antihypertensives are effective at lowering blood pressure, they don’t necessarily target vascular stiffening and as such new therapeutic approaches are sought.

Hence, we are studying the impact of chemokines released from macrophages on fibrosis and collagen generation, which may lead to the development of more effective therapies for hypertension.

We have exciting new data to suggest that human macrophages release high concentrations of a chemokine, CCL18 which activates the G-protein coupled receptor, CCR8 leading to an elevation in blood pressure and associated end-organ damage. We hypothesise that pharmacological targeting of the CCL18-CCR8 axis will reverse hypertension and associated cardiovascular and renal fibrosis, protect against end-organ damage and limit hypertension-induced brain inflammation.

2. Role of the inflammasome in the pathogenesis of pulmonary hypertension

Pulmonary hypertension is an incurable disease, and a major cause of death, and although rare, prognosis is extremely poor. 5-year survival is ~50% and those affected suffer a significantly reduced quality of life. The unfavourable outcomes are due primarily to the fact that the currently approved drugs are pulmonary vasodilators which modestly lower mean pulmonary arterial pressure, yet have a limited ability to reverse the underlying pathological remodeling. To advance therapy, new treatments which target remodelling in the pulmonary vasculature and/or right ventricle are urgently needed.

New therapeutic strategies are urgently needed. Our research group has recently demonstrated that the NLRP3 inflammasome, which is highly expressed in macrophages, and its downstream cytokine, IL-18 play a key role in the end-organ damage associated with pulmonary hypertension. It is hypothesised that inhibition of the NLRP3 inflammasome and/or IL-18 signalling will attenuate pulmonary hypertension and the accompanying cardiopulmonary remodelling.

3. Using stem cell-derived exosomes to improve ischaemic stroke outcome

Stroke is a debilitating disease that can cause permanent neurological damage, complications, and death. At present, there are very few treatment options available for patients, thus the development of new treatments is vital to reduce the damage caused by stroke.

Recent findings by our research group has found that acute post-stroke administration of stem cell-derived exosomes can limit functional impairment and cerebral infarct damage as well as reduce the infiltration of leukocytes into the ischaemic hemisphere. However, the ideal clinical therapeutic would be one that could improve longer-term functional recovery when administration is given several hours/days after a stroke. It is hypothesized that delayed post-stroke treatment of stem cell-derived exosomes can improve long-term stroke outcomes.

4. Examining post-stroke relaxin therapy following ischaemic stroke

Relaxin is a peptide hormone known for its pleiotropic properties, including anti-inflammatory, anti-apoptotic and angiogenic effects, thus it may provide neuroprotection post-stroke. Administration of relaxin prior to stroke has been shown to decrease cerebral infarct size, however, it remains unclear if post-stroke administration of relaxin is neuroprotective. It is hypothesised that post-stroke administration of relaxin will provide functional recovery and reduce brain injury and infiltrating immune cells into the ischaemic brain.

Visit Associate Professor Kemp-Harper's and Dr Broughton's Monash research profiles to see a full listing of current projects.

Techniques/expertise

Chronic Hypoxia-induced pulmonary hypertension
Ang II-Induced hypertension
Stroke surgeries (middle cerebral artery occlusion and photothrombotic stroke)
Neurological/functional testing
Wire myography
Molecular approaches (PCR and Western blotting)
Histochemical analysis (histochemistry and immunohistochemistry)
Flow cytometry
Superoxide detection

Disease models

Pulmonary hypertension
Systemic hypertension
Ischemic stroke


Collaborations

We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on Associate Professor Barbara Kemp-Harper's map and Dr Brad Broughton's map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).

A/Prof Barbara Kemp-Harper
Dr Brad Broughton (Biomedicine Discovery Institute, Monash University)
Dr Jane Bourke (Biomedicine Discovery Institute, Monash University)
Professor Grant Drummond (Dept of Physiology, Anatomy & Microbiology, La Trobe University)
Dr Tracey Gaspari (Biomedicine Discovery Institute, Monash University)
Professor Adrian Hobbs (William Harvey Research Institute, London)
Dr Francine Marques (School of Biological Sciences, Monash University)
Professor Rebecca Ritchie (Baker Heart & Diabetes Institute, Melbourne)
Professor Avril Robertson (School of Chemistry & Molecular Biosciences, University of Queensland)
Associate Professor Chrishan Samuel (Biomedicine Discovery Institute, Monash University)
Associate Professor Martin Stone (Biomedicine Discovery Institute, Monash University)
Professor Robert Widdop (Biomedicine Discovery Institute, Monash University)
Dr Antony Vinh (Dept of Physiology, Anatomy & Microbiology, La Trobe University)

Dr Brad Broughton
Associate Professor Barbara Kemp-Harper (Biomedicine Discovery Institute, Monash University)
Professor Chris Sobey (Dept of Physiology, Anatomy & Microbiology, La Trobe University)
Associate Professor Rebecca Lim (Ritchie Centre, Hudson Institute of Medical Research/Monash University)
Professor Mibel Aguilar (Dept of Biochemistry, Monash University)
Professor John Forsythe (Dept of Material Science & Engineering, Monash University)
Dr Mark Del Borgo (Dept of Biochemistry, Monash University)
Professor Robert Widdop (Biomedicine Discovery Institute, Monash University)
Professor Glenn King (Institute of Molecular Bioscience, University of Queensland)
Dr Lachlan Rash (School of Biomedical Science, University of Queensland)
Associate Professor Chrishan Samuel (Biomedicine Discovery Institute, Monash University)
Associate Professor Christoph Hagemeyer (Australian Centre for Blood Diseases, Monash University)
Dr Be’eri Niego (Australian Centre for Blood Diseases, Monash University)


Student research projects

The Kemp-Harper and Broughton Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.

Please visit Associate Professor Barbara Kemp-Harper's Supervisor Connect and Dr Brad Broughton's Supervisor Connect to explore the projects currently available in our Lab.