Research

Widdop Lab research

Collaborations | Student research projects | Publications

About Professor Robert Widdop

Professor Robert Widdop obtained his PhD at Monash University, Department of Pharmacology. He has worked in the Clinical Pharmacology Unit at the Austin Hospital, University of Melbourne, and was appointed as a Wellcome Trust Postdoctoral Fellow in the Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen’s Medical Centre Nottingham, UK, under the guidance of Professors Terrance Bennett and Sheila Gardiner, where he honed his expertise for using integrative pharmacology in chronic preclinical studies.

Prof Widdop returned to Monash University and held several prestigious full-time Research Fellowships (NHMRC RD Wright Fellowship; NHMRC Research Fellowship; NHMRC Senior Research Fellowship). In 2001, he was appointed as a Teaching and Research academic in the Department of Pharmacology and is currently Head of Department of Pharmacology (since 2011) and on the Executive of the Biomedicine Discovery Institute (BDI) and a senior member of the Cardiovascular Disease Program of the BDI.

Prof Widdop established the Integrative Cardiovascular Pharmacology Lab which has a major focus on the biology and pathophysiology of the renin-angiotensin system (RAS) and its involvement in cardiovascular, renal and lung diseases. More recently, his lab has been pursuing drug discovery targets of less-studied aspect of the RAS. Prof Widdop has been an international leader in angiotensin AT2 receptor research and has contributed key research that underpins the development of AT2R agonists to treat organ fibrosis. Other work has identified insulin-regulated aminopeptidase (IRAP) as a novel target for fibrosis, where Prof Widdop is one of 4 founders of a spinout company, Inosi Therapeutics, which is backed by Monash University and venture capital company, IP Group.

Prof Widdop prides himself on providing a collaborative and collegial workplace for staff and research students. In 2019, he was awarded both the Dean’s Award and the Vice Chancellor’s Award for Excellence in Honours (4^th-year research students) Supervision; Monash University.

Our research

The Integrative Cardiovascular Pharmacology Lab investigates novel mechanisms and pathways of the RAS using techniques ranging from molecular/cellular through to in vivo preclinical models that mimic clinical disease settings and pathology. It is well recognised that hypertension (and/or other comorbidities) drives end organ damage (inflammation and fibrosis) and, consequently, organ dysfunction. While conventional anti-hypertensive drugs lower blood pressure, they generally do not correct underlying aberrant fibrosis.

Two major themes are directed towards the pharmacology and pathophysiology related to the AT2 receptor and IRAP, as novel drug targets. Our goal is to develop new anti-fibrotic therapies to treat a number of clinical diseases complicated by aberrant fibrosis. More broadly, our research covers numerous models of cardiovascular and renal diseases including hypertension, heart failure, atherosclerosis, chronic kidney disease, stroke, diabetes, and obesity-driven liver disease.

Current projects

AT2R and IRAP drug discovery programs and drug delivery mechanisms
AT2R and IRAP as therapeutic targets modulating extracellular matrix in vital organs related to cardiopulmonary, kidney, metabolic and vascular diseases
Role of AT2R in cardiac, kidney, lung and liver fibrosis
Role of AT2R and IRAP in stroke and the brain-cardiac axis
Role of IRAP in cardiac and kidney fibrosis and diabetic complications

Visit Professor Widdop's Monash research profile to see a full listing of current projects.

Research activities

Drug discovery

Understanding mechanisms of action of AT2R and IRAP ligands in bespoke cell-based assays that inform on key pathways and drug screening assays.

Hypertension-related target organ damage

Using preclinical hypertensive models with/ without comorbidities such as kidney disease, diabetes (T1D, T2D), our research programs are designed to interrogate the ability of novel drug to slow and reverse disease pathology and improve organ function

Role of AT2R in inflammation and fibrosis

After its initial discovery in 2004, the AT2R agonist, C21, has recently entered clinical trials for idiopathic pulmonary fibrosis (IPF), validating preclinical data demonstrating that AT2R stimulation is an important therapeutic strategy to treat extracellular matrix dysregulation. Our group has a library of novel AT2R-selective ligands that are being explored in human primary cells and tissue (lung, liver) related to IPF and non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Preclinical projects also use a transformative, rapid technique for inducing myocardial infarction (MI) that results in heart failure.

Role of IRAP in inflammation and fibrosis

Our group is pioneering novel IRAP ligands for the treatment of cardiovascular and renal diseases. Our academic research has led to the development of first-in-class compounds that are being investigated in preclinical research programs that are initially focused on cardiac and kidney disease, including end organ complications of type 1 and type 2 diabetes.

^{Heart imaging}

^{Cross-section heart- fibrosis (collagen) around coronary artery and in heart (red)}

^{Isolated cardiomyocytes secreting collagen}


^{Blood pressure}	^{Brain infarct after stroke}	^{Atherosclerotic lesion}

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 the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).

Dr Jennifer Callaway (Department of Pharmacology, University of Melbourne)
Professor Kate Denton (Department of Physiology, Monash BDI)
Professor Mibel Aguilar (Department of Biochemistry & Molecular Biology, Monash BDI)
Professor Patrick Perlmutter (School of Chemistry, Monash University)
Associate Professor Siew Yeen Chai (Department of Physiology, Monash BDI)
Associate Professor Barb Kemp-Harper (Department of Pharmacology, Monash BDI)
Associate Professor Chrishan Samuel (Department of Pharmacology, Monash BDI)
Dr Anthony Dear (ECRU Biotechnology Group, Australian Centre for Blood Diseases)
Professor Arthur Christopoulos (Department of Pharmacology & MIPS, Parkville, Monash University)
Professor Walter Thomas (School of Biomedical Science, University of Queensland)
Professor Jaye Chin-Dusting (BakerIDI Heart & Diabetes Institute, Melbourne)
Dr Jennifer Irvine (BakerIDI Heart & Diabetes Institute, Melbourne)
Professor Geoff Head (BakerIDI Heart & Diabetes Institute, Melbourne)
Dr Daniel Henrion (University of Angers, France)
Dr Muscha Steckelings (Center for Cardiovascular Research, Charité-Universitätsmedizin Berlin, Germany)

Student research projects

The Widdop 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 Supervisor Connect to explore the projects currently available in our Lab.