A/Professor Salvatore Pepe

Biography:

Assoc/Prof. Salvatore Pepe is a clinical scientist who leads the Molecular & Cellular Cardiology Laboratory in the Heart Research Group (Clinical Sciences Theme) at the Murdoch Children's Research Institute (MCRI) and is a clinical research manager in the Department of Cardiology, Royal Children's Hospital.

After initially training in clinical pharmacology and biochemistry and completing a doctorate in cardiovascular physiology he undertook four years post-doctoral training (NIH Fogarty Postdoctoral Fellow) at Johns Hopkins Hospital, Bayview Campus, Baltimore, USA, in the NIH, National Institute on Aging Intramural Research Program (Cardiovascular Science).

Previous to working at Melbourne Children's Campus he was Head of the Cardiothoracic Surgical Research Laboratory, (Dept of Cardiothoracic Surgery), at the Alfred Hospital, and Adjunct Senior Lecturer, Department of Surgery (Alfred), Monash University, Melbourne, involved in clinical trial and laboratory research focused on cellular and mitochondrial processes in heart failure, transplantation, and cardiopulmonary bypass surgery.

Working with cardiac surgery, cardiology and intensive care clinicians, Dr Pepe's work is focused on cardiovascular complications arising from congenital and acquired heart and lung disorders, premature birth and surgical interventions. The emphasis of the research effort is to translate new understanding of disease mechanisms and novel therapeutic agents to clinical use. Currently he is investigating the safety and efficacy of cord blood stem cell therapy as an adjunct to cardiopulmonary bypass surgery in children with severe heart malformations (i.e. hypoplastic left heart syndrome) or with cardiomyopathy. The research program over the past decade spans from in vitro and in vivo laboratory studies to clinical trials.

A/Prof Pepe has served NHMRC, NHF and ARC as a panel member and external reviewer, and is an invited reviewer for numerous medical and scientific journals. Currently he is an Associate Editor of Heart Lung and Circulation (Elsevier) and Clinical and Experimental Pharmacology and Physiology (Wiley), and also an editorial board member of the Journal of Molecular and Cellular Cardiology (Elsevier) and Heliyon (Elsevier). He is Past-President of the International Society for Heart Research and in 2016 was awarded the ISHR Distinguished Leader Award.

Other Affiliations:

Honorary Affiliations:

Principal Fellow, Department of Paediatrics, University of Melbourne
Associate Editor, Heart Lung and Circulation, (Elsevier)
Associate Editor, Clinical and Experimental Pharmacology and Physiology (Wiley-Blackwell)
Editorial Board, Journal of Cellular & Molecular Cardiology (Elsevier)
World Council Member and Past-President, International Society for Heart Research

Awards:

2001: Speaker Medal of Merit, St Boniface Hospital Cardiovascular Institute, Canada
2006: Tony Charlton Surgical Research Award, Alfred Hospital, Melbourne, Australia
2006: Fellowship of the American Heart Association
2007: Fellowship of the Cardiac Society of Australia & New Zealand
2008: Fellowship of the Society for Gerontological Cardiology (USA)
2016: Distinguished Leader Award, International Society for Heart Research World Congress

Research:

Clinical translation and clinical trial studies - cardiomyopathy and other heart failure -acquired or congenital heart conditions
Cord blood stem cell therapy
Exosomal and paracrine regulatory actions of cord blood stem cells on growth and repair mechanisms in the heart and cardiovasculature.
Mitochondrial metabolism and dynamics in heart injury and adaptive remodelling.
Mitochondria as a therapeutic target in ischemic/hypoxic injury and heart failure
Post-cardiopulmonary bypass surgery low cardiac output syndrome

Projects:

Cord blood stem cell therapy in new-borns and older children at risk of heart failure (severe congenital heart disease or cardiomyopathy).
Cellular and mitochondrial mechanisms regulating adaptive processes during disease progression and therapeutic interventional procedures.
Mitochondrial protein therapy for cardiomyopathy.
Novel therapeutics for cancer-therapy-induced mitochondrial cardiomyopathies.
Role of betamethasone steroid therapy in fetal and neonatal cardiopulmonary development and premature birth complications.

Pepe S. Raising the Dead: Mitochondrial Cardiolipin as a Key Target for Post-Cardiac Arrest Resuscitation, Ischaemia-Reperfusion Injury and Cardiomyopathy. Heart Lung Circ. 2019;28(3):360-363.

Krauss RH, Phipson B, Oshlack A, Prasad-Gupta N, Cheung MM, Smolich JJ, Pepe S. Shifts in ovine cardiopulmonary microRNA expression in late gestation and the perinatal period. PLoS One. 2018;13(9):e0204038. doi: 10.1371/journal.pone.0204038.

Bernasochi GB, Boon WC, Curl CL, Varma U, Pepe S, Tare M, Parry LJ, Dimitriadis E, Harrap SB, Nalliah CJ, Kalman JM, Delbridge LMD, Bell JR. Pericardial adipose and aromatase: A new translational target for aging, obesity and arrhythmogenesis? J Mol Cell Cardiol. 2017;111:96-101.

Sheeran FL, Pepe S. Mitochondrial Bioenergetics and Dysfunction in Failing Heart. Adv Exp Med Biol. 2017;982:65-80.

Pepe S, Cheung MM. Gaps between the Teeth of Cardiovascular Health Strategy. Heart Lung Circ. 2017;26(1):1-5.

Pepe S. Mitochondria "muscle in" as a potential adjunct therapy in cardiothoracic surgery. J Thorac Cardiovasc Surg. 2017;153(4):944-946.

McLennan PL, Pepe S. Prescribing More Stringent Design of Randomized Clinical Trials of Omega-3 Polyunsaturated Fatty Acids. Mayo Clin Proc. 2017;92(6):1005-1006.

Ip WTK, Chandramouli C, Smith JA, McLennan PL, Pepe S, Delbridge LMD. A Small Cohort Omega-3 PUFA Supplement Study: Implications of Stratifying According to Lipid Membrane Incorporation in Cardiac Surgical Patients. Heart Lung Circ. 2017;26(8):846-855.

Sheeran FL, Pepe S. Posttranslational modifications and dysfunction of mitochondrial enzymes in human heart failure. Am J Physiol Endocrinol Metab. 2016; 311(2): E449-60.

Ip WT, McAlindon A, Miller SE, Bell JR, Curl CL, Huggins CE, Mellor KM, Raaijmakers AJ, Bienvenu LA, McLennan PL, Pepe S, Delbridge LM. Dietary omega-6 fatty acid replacement selectively impairs cardiac functional recovery after ischemia in female (but not male) rats. Am J Physiol Heart Circ Physiol. 2016 Sep 1;311(3):H768-80.

Brizard CP*, Looi JY* equal first author, Smolich JJ, Horton SB, Angerosa J, Elwood NJ, Pepe S. Safety of Intracoronary Human Cord Blood Stem Cells in a Lamb Model of Infant Cardio-pulmonary Bypass. Ann Thorac Surg. 2015; 100: 1021-1029.

Pepe S, Mentzer RM Jr, Gottlieb RA. Cell-permeable protein therapy for complex I dysfunction. J Bioenerg Biomembr. 2014; 46: 337-45

Pepe S. Omentin on a Four-Pronged Fork: Another Reason Why Obesity Erodes Cardiovascular Survival. Heart Lung Circ. 2014; 23: 791-793.

Marasco SF, Sheeran FL, Chaudhuri K, Vale M, Bailey M, Pepe S. Molecular markers of programmed cell death in donor hearts prior to transplantation. Journal of Heart and Lung Transplantation. 2014; 33: 185-93

Liaw NY, Hoe LS, Sheeran FL, Peart JN, Headrick JP, Cheung MMH, Pepe S. Postnatal shifts in ischemic tolerance and cell survival signaling in murine myocardium. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. 2013; 305: R1171-R1181

Looi YJ, Elwood NJ, Brizard CP, Pepe S. Developing stem cell therapeutics for the heart also requires targeting non-myocytes. Heart, Lung and Circulation. 2013; 22: 975-979

Pepe S, Liaw NY, Hepponstall M, Sheeran FL, Yong MS, d'Udekem Y, Cheung MM, Konstantinov IE. Effect of remote ischemic preconditioning on phosphorylated protein signaling in children undergoing tetralogy of fallot repair: A randomized controlled trial. Journal of the American Heart Association. 2013;2:e000095

Jones BO, Pepe S, Sheeran FL, Donath S, Hardy P, Shekerdemian L, Penny DJ, McKenzie I, Horton S, Brizard CP, d'Udekem Y, Konstantinov IE, Cheung MM. Remote ischemic preconditioning in cyanosed neonates undergoing cardiopulmonary bypass: A randomized controlled trial. The Journal of Thoracic and Cardiovascular Surgery. 2013; 46: 1334-1340

Ke BX*, Pepe S* equal first author, Grubb DR, Komen JC, Laskowski A, Rodda FA, Hardman BM, Pitt JJ, Ryan MT, Lazarou M, Koleff J, Cheung MMH, Smolich JJ, Thorburn DR. Tissue-specific splicing of an Ndufs6 gene-trap insertion generates a mitochondrial complex I deficiency-specific cardiomyopathy. Proceedings National Academy of Sciences USA. 2012; 109: 6165-6170

Canton M, Menazza S, Sheeran FL, Polverino de Laureto P, Di Lisa F, Pepe S. Oxidation of myofibrillar proteins in human heart failure. Journal of the American College of Cardiology. 2011;57:300-309

Funding: