Profile
I completed my medical degree at the University of Melbourne in 1978 and qualified as a Specialist Renal Physician in 1985. My medical research career began with a PhD under the supervision of the late Professor Austin Doyle, after which I spent 3 years in the Medical Research Council Blood Pressure Unit in Glasgow as an NHMRC Neil Hamilton Fairley Traveling Fellow. I returned to the Department of Medicine at the Austin Hospital in 1989 and became an NHMRC R D Wright Fellow until 1995 when I was appointed as Professor of Physiology. My research interests are in the genetics of common conditions and I am also involved in international clinical trials. I retain a clinical role as a Consultant Physician at the Royal Melbourne Hospital. My favorite pastimes are fishing, tennis, surfing and golf.
Qualifications:
MBBS
PhD
FRACP
Teaching
Departmental Curriculum Coordinator
Convenor & Lecturer:
510-110 Principles of Biomedical Science (Medicine)
511-121 Introduction to Biomedical Science (Dental Science)
513 111 Principles of Biomedical Science (Physiotherapy)
536-350 Genes to Phenotype: Control & Integration (Biomedical Science)
Lecturer:
536-201 Principles of Physiology (Science)
536-206 Physiology (Optometry)
511-224 Oral Health Sciences 2A (Dental Science)
536-211 Physiology: Control of Body Function (Science)
510-210 Cardiorespiratory & Locomotor Systems (Medicine)
513-211 Cardiorespiratory Systems (Physiotherapy)
536-250 Integrated Biomedical Science (Biomedical Science)
536-301 Integrative Physiology: Heart & Kidney (Science)
536-311 Molecular/Cellular Basis of Physiology (Science)
Service to the University, discipline
or community and recent presentations
I am involved in a wide range of Departmental, Faculty and University Committees.
I serve on the editorial boards of the following journals:
Clinical and Experimental Hypertension
Clinical and Experimental Pharmacology and Physiology
Hypertension
Hypertension Research
Nephrology
Physiological Genomics
I regularly review research applications for national and international funding bodies.
I am closely involved with cognate professional societies and with meeting organization.
I am a founding trustee of the Foundation for High Blood Pressure Research that was formed after the 1994 International Society of Hypertension meeting and has funded numerous research fellowships to outstanding young scientists in the field.
Recent Research Presentations:
Genetic markers for retinal arteriolar narrowing and risk of hypertension and cardiovascular disease. Wong, Harrap, Wang, Baird, Mitchell, Liew. National Health & Medical Research Council of Australia, 2008-2010
Research
Profile, Interests and Recent Publications
My research is the genetics of common conditions. This largely done through family studies but also involves animal-breeding work as well.
1990 I established the Victorian Family Heart Study (VFHS) and after 6 years we successfully recruited approximately 3000 healthy adults who comprised about 800 families (each of mum, dad and at least 1 natural offspring). These families were enriched by the inclusion of families with twins. For this we are indebted to Professor John Hopper and the Australian Twin Registry. The result is a unique resource for studying the genetic and environmental factors that determine simple traits such as blood pressure, heart rate, weight, height, cholesterol, baldness and fibrinogen. To do so we have taken advantage of the most modern technology and brought together a team with skills in molecular biology and genetic biostatistics.
The VFHS is renown internationally for its discoveries in relation to blood pressure and the Y chromosome, baldness and the androgen receptor gene, the genetics of height and ongoing studies of cardiovascular risk factors.
I work closely on these studies with Dr Justine Ellis, who is now at the Murdoch Children’s Research Institute, and Dr Katrina Scurrah, who is now a lecturer in the School of Population Health. Justine is the molecular biology expert in our team and Katrina is the biostatistical expert.
To complement the VFHS focus on risk factors, I established the Acute Myocardial Infarction Genetic Origins (AMIGO) Study looking at the genetics of heart attack (acute coronary syndrome). This was one of the first studies in the world to report genome wide linkage for this condition that remains the single most common cause of death.
To understand the genetic basis of heart size (which after age is the single most important cardiovascular risk factor), I initiated series of breeding studies in rats in 1989. This resulted in the first identification by genome wide scanning of a gene that controls heart size independent of blood pressure. Our more recent studies are homing in on the precise gene and mutation that explain this action.
The breeding continued down a parallel track to produce a new strain of rat that has normal blood pressure but a big heart. These Hypertrophic Heart Rats (HHR) have very greatly enlarged heart muscle cells and the challenge now is to understand the exact developmental and physiological mechanism. We collaborate with Associate Professor Lea Delbridge (Department of Physiology) and Professor Walter Thomas (University of Queensland) in these studies that are revealing some very interesting features regarding the origins of big hearts.
The funding for the family and breeding studies has been generously provided from a variety of sources including the National Health and Medical Research Council, the Victorian Health Promotion Foundation, the Australian Research Council, the National Heart Foundation, the Cabrini Medical Education & Research Foundation and the Clive & Vera Ramaciotti Foundation.
I have also been closely involved in 2 large clinical trials – the PROGRESS and ADVANCE Studies. These trials have examined the prevention of cardiovascular disease in those at high risk as a result of either a prior stroke (PROGRESS) or type 2 diabetes (ADVANCE). The George Institute in Sydney leads these trials that are worldwide and have involved over 17,000 patients in all. The results of these trials have been published in the Lancet and New England Journal of Medicine. They are changing the international guidelines regarding the prevention of cardiovascular disease in high-risk individuals.
Recent Publications:
Ellis JA, Scurrah KJ, Duncan AE, Lamantia A, Byrnes GB, Harrap SB. Comprehensive multi-stage linkage analysis to identify a locus for adult height on chromosome 3 in a healthy Caucasian population. Human Genetics. 2007;121:213-222
Büsst CJ, Scurrah KJ, Ellis JA, Harrap SB. Selective genotyping reveals association between the epithelial sodium channel γ-subunit and systolic blood pressure. Hypertension. 2007;50:672-678.
Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, Harrap S, Poulter N, Marre M, Cooper M, Glasziou P, Grobbee DE, Hamet P, Heller S, Liu LS, Mancia G, Mogensen CE, Pan CY, Rodgers A, Williams B. Effects of fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised control trial. Lancet. 2007;370:829-840
Tzourio C, Arima H, Harrap S, Anderson C, Godin O, Woodward M, Neal B, Bousser MG, Chalmers J, Cambien F, MacMahon S. APOE genotype, ethnicity, and the risk of cerebral hemorrhage. Neurology. 2008;70:1322-1328
Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu LS, Mancia G, Mogensen CE, Pan CY, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. New England Journal of Medicine. 2008;24:2560-2572
Bell J, Porello E, Huggins K, Harrap SB, Delbridge LM. The intrinsic resistance of female hearts to an ischemic insult is abrogated in primary cardiac hypertrophy. Am J Physiol. 2008;294:H1514-H1522
Zentner D, du Plessis M, Brenneke S, Wong J, Grigg L, Harrap S. Deterioration in cardiac systolic and diastolic function late in normal human pregnancy. Clin Sci. 2008;116:599-606
Porrello ER, Bell JR, Schertzer JD, Curl CL, McMullen JR, Mellor KM, Ritchie RH, Lynch GS, Harrap SB, Thomas WG, Delbridge LMD. Heritable pathologic cardiac hypertrophy in adulthood is preceded by neonatal cardiac growth restriction. Am J Physiol. 2009 in press
Yip L, Zaloumis S, Irwin D, Severi G, Hopper J, Giles G, Harrap S, Sinclair R, Ellis J. Gene-wide association study of the aromatase gene (CYP19A1) with female pattern hair loss. Br J Dermatol. 2009 in press
Porrello ER, D’Amore A, Curl CL, Allen AM, Harrap SB, Thomas WG, Delbridge LMD. Cardiomyocyte autophagy is mediated by the angiotensin II type 1 receptor and antagonized by the type 2 receptor. Hypertension. 2009 in press
De Galan B, Perkovic V, Ninomiya T, Pillai A, Patel A, Cass A, Neal B, Poulter N, Harrap S, Mogensen CE, Cooper M, Marre M, Williams B, Hamet P, Mancia G, Woodward M, Glasziou P, Grobbee D, MacMahon S, Chalmers J for the ADVANCE Collaborative Group. Lowering blood pressure reduces renal events in Type 2 diabetes. J Am Soc Nephrol. 2009 in press
Currently
Supervised Staff/Students
Angela Lamantia
Mirek Kapuscinski
