Professor David Thorburn

contact details

Thorburn 4

  Professor David Thorburn
  Theme Director - Genetics 
  Murdoch Childrens Research Institute
  Department of Paediatrics, University of Melbourne
  Royal Children's Hospital
  Flemington Road
  Victoria, 3052

  T +61 3 8341 6235


David Thorburn received his PhD in Biochemistry from the University of Sydney in 1987 before completing Fulbright and NHMRC CJ Martin Fellowships with Ernie Beutler at Scripps Clinic, La Jolla, California. He returned to Australia in 1990 and is currently an NHMRC Principal Research Fellow, a Fellow and past-President of the Human Genetics Society of Australasia and a Founding Fellow of the Faculty of Science of the Royal Australasian College of Pathologists.

His group is primarily involved in researching the genetic basis of mitochondrial energy generation disorders, but also acts as the national referral centre for the diagnosis of mitochondrial disease in children. David has published over 140 research papers, including recent papers in Nature Genetics, Cell Metabolism, Science Translational Medicine and Proceedings of the National Academy of Sciences(USA). He supervises postdoctoral Fellows, PhD and Honours students and leads the Murdoch Childrens Research Institute Genomics and Personalised Medicine Research Affinity Group.


2007 - 2016 NHMRC Principal Research Fellow
2007 - 2009 President, Human Genetics Society of Australasia
2007 Sutherland Lecturer, Human Genetics Society of Australasia

2012 David Danks Oration, University of Melbourne

2010 - 2014 Invited speaker at 14 international conferences in the fields of Mitochondrial Disease, Inherited Metabolic Diseases, Child Neurology, Gastroenterology and Nephrology in Norway, Netherlands, Japan, USA, China, Taiwan and Australia


research focus & interest

David Thorburn's research has focused on inherited metabolic disorders, particularly those affecting mitochondrial energy generation, which comprise more than 150 monogenic disorders. His laboratory acts as the Australasian referral centre for children suspected of mitochondrial disease and has diagnosed over 500 patients. Through studies in-house and with collaborators we have identified disease-causing mutations in over 280 of these patients in a total of 8 mtDNA genes, 25 nuclear genes in which mutations had previously been described and 15 novel nuclear disease genes, including 5 of the 9 known Complex I assembly defect genes.

Recent gene identification studies have used "Next Generation" DNA sequencing to sequence mitochondrial DNA and over 1000 nuclear genes encoding all known mitochondrial proteins in patients. Our bioinfomatic and experimental studies provide an "all comers" approach intended to be suitable for studying blood from any child with mitochondrial disease, irrespective of family history, and aiming to spare the need for invasive procedures such as muscle biopsy. A major goal is to translate this from being a research tool to clinical use, a challenge requiring collaboration between laboratory scientists, clinicians, public health, ethics and education researchers.

Another long-standing research interest has been to understand the transmission of mitochondrial DNA mutations and translate this knowledge into approaches for prenatal diagnosis and prevention, such as pre-implantation genetic diagnosis. Aside from genetics, we also have a substantial involvement in studying cellular and animal models of mitochondrial disorders. These include 2 mouse models of mitochondrial Complex I deficiency, which are being used to improve our understanding of the precise disease mechanisms and to trial dietary and pharmaceutical treatment strategies.

tier 1 and 2 publications

Chinnery P, Majamaa K, Turnbull D and Thorburn D (2006) Treatment for mitochondrial disorders. Cochrane Database Syst. Rev. 2006, Issue 1. Art. No.:CD004426

Hui J, Kirby DM, Thorburn DR and Boneh A (2006) Decreased respiratory chain enzyme activities in "non-mitochondrial" diseases. Dev Med Child Neurol 48: 132-136

Pagnamenta AT, Taanman JW, Wilson CJ, Anderson N, Marotta R, Duncan AJ, Bitner-Glindzicz M, Taylor RW, Laskowski A, Thorburn DR and Rahman S (2006) Dominant inheritance of premature ovarian failure associated with mutant mitochondrial DNA polymerase gamma. Hum.Reprod. 21: 2467-2473

Loupatty FJ, Clayton PT, Ruiter JP, Ofman R, Ijlst L, Brown GK, Thorburn DR, Harris RA, Duran M, Desousa C, Krywawych S, Heales SJ and Wanders RJ (2007) Mutations in the Gene Encoding 3-Hydroxyisobutyryl-CoA Hydrolase Results in Progressive Infantile Neurodegeneration. Am J Hum Genet 80: 195-199

Yaplito-Lee J, Weintraub R, Jamsen K, Chow CW, Thorburn DR, Boneh A (2007) Cardiac manifestations in oxidative phosphorylation disorders of childhood. J Pediatr 150: 407-411

Dunning CJR, McKenzie M, Sugiana C, Lazarou M, Silke J, Connelly A, Fletcher JM, Kirby DM, Thorburn DR and Ryan MT (2007) Human CIA30 is involved in the early assembly of mitochondrial Complex I and mutations in its gene cause disease. EMBO J. 26: 3227-3237

Gibson K, Halliday JL, Kirby DM, Yaplito-Lee J, Thorburn DR and Boneh A (2008) Mitochondrial Oxidative Phosphorylation Disorders Presenting in Neonates: Clinical Manifestations and Enzymatic and Molecular Diagnoses. Pediatrics 122:1003-1008

Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong SE, Walford GA, Sugiana C, Boneh A, Chen WK, Hill DE, Vidal M, Evans JG, Thorburn DR, Carr SA and Mootha VK (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134: 112-123

Sugiana C, Pagliarini DJ, McKenzie M, Kirby DM, Salemi R, Abu-Amero KK, Dahl HHM, Hutchison WM, Vascotto KA, Smith SM, Newbold RF, Christodoulou J, Calvo S, Mootha VK, Ryan MT and Thorburn DR (2008) Mutation of C20orf7 disrupts Complex I assembly and causes lethal neonatal mitochondrial disease. Am J Hum Genet 83: 468-478

Drenckhahn JD, Schwarz QP, Gray S, Laskowski A, Kiriazis H, Ming Z, Harvey RP, Du XJ, Thorburn DR and Cox TC (2008) Compensatory growth of healthy cardiac cells in the presence of diseased cells restores tissue homeostasis during heart development. Developmental Cell 15: 521-533

Coughlan MT, Thorburn DR, Penfold SA, Laskowski A, Harcourt BE, Sourris KC, Tan ALY, Fukami K, Thallas-Bonke V, Nawroth PP, Brownlee M, Bierhaus A, Cooper ME, Forbes JM (2009) RAGE-Induced Cytosolic Oxidative Disturbances Amplify Mitochondrial Superoxide Generation in Diabetic Nephropathy. J Am Soc Nephrol 20:742-752

Riley LG, Cooper S, Hickey P, Rudinger-Thirion J, McKenzie M, Compton A, Lim SZ, Thorburn DR, Ryan MT, Giegé R, Bahlo M, Christodoulou J (2010) A Mitochondrial Tyrosyl-tRNA Synthetase (YARS2) Mutation is a Novel Cause of Myopathy, Lactic Acidosis and Sideroblastic Anaemia (MLASA). Am J Hum Genet 87: 52-59

Calvo SE, Tucker EJ, Compton AG, Kirby DM, Crawford G, Burtt NP, Rivas MA, Guiducci C, Goldberger OA, Redman MC, Wiltshire E, Wilson CJ, Altshuler D, Gabriel SB, Daly MJ, Thorburn DR and Mootha VK (2010) High-throughput, pooled sequencing of a patient cohort reveals mutations in NUBPL and FOXRED1 that cause human complex I deficiency. Nat Genet 42: 851-858

Tuppen HAL, Hogan VE, He L, Blakely EL, Worgan L, Al-Dosary M, Saretzki G, Alston CL, Morris AA, Clarke M, Jones S, Devlin AM, Mansour S, Chrzanowska-Lightowlers ZMA, Thorburn DR, McFarland R and Taylor RW (2010) The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families. Brain 133: 2952-2963

Carranza Rojo D, Hamiwka L, McMahon JM, Dibbens LM, Arsov T, Suls A, Stodberg T, Kelley K, Wirrell EC, Appleton B, Mackay MT, Freeman JL, Yendle SC, Berkovic SF, Bienvenu T, De Jonghe P, Thorburn DR, Mulley JC, Mefford HC and Scheffer IE (2011) De Novo SCN1A mutations in Migrating Partial Seizures of Infancy. Neurology 77:380-383

Tucker EJ, Hershman SG, Köhrer K, Belcher-Timme CA, Patel J, Goldberger OA, Christodoulou J, Silberstein JM, McKenzie M, Ryan MT, Compton AG, Jaffe JD5, Carr SA, Calvo SE, RajBhandary UL, Thorburn DR, Mootha VK (2011) Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation. Cell Metabolism 14: 428-434

Calvo SE, Compton AG, Hershman SG, Lim SC, Lieber DS, Tucker EJ, Laskowski A, Garone C, Liu S, Jaffe DB, Christodoulou J, Fletcher JM, Bruno DL, Goldblatt J, DiMauro S, Thorburn DR and Mootha VK* (2012) Molecular Diagnosis of Infantile Mitochondrial Disease with Targeted Next-Generation Sequencing.Science Trans Med4: 118ra10

Ke BX, Pepe S, Grubb DR, Komen JC, Laskowski A, Rodda FA, Hardman BM, Pitt JJ, Ryan MT, Lazarou M, Koleff J, Cheung MMH, Smolich JJ and Thorburn DR (2012) Tissue-specific splicing of anNdufs6Gene-trap insertion generates a mitochondrial Complex I deficiency-specific cardiomyopathy.Proc Natl Acad Sci USA109:6165-6170

Pfeffer G, Majamaa K, Turnbull DM, Thorburn D and Chinnery PF (2012) Treatment for mitochondrial disorders.Cochrane Database Syst Rev.2012 Apr 18;4:CD004426

Lim SC, Friemel M, Marum JE, Tucker EJ, Bruno DL, Riley LG, Christodoulou J, Kirk EP, Boneh A, DeGennaro C, Springer M, Mootha VK, Rouault TA, Leimkühler S, Thorburn DR, Compton AG. (2013) Mutations in LYRM4, encoding iron-sulfur cluster biogenesis factor ISD11, cause deficiency of multiple respiratory chain complexes.  Hum Mol Genet  22: 4460-4473

Gaignard P, Menezes M, Schiff M, Bayot A, Rak M, Ogier de Baulny H, Su CH, Gilleron M, Lombes A, Abida H, Tzagoloff A, Riley L, Cooper ST, Mina K, Davis MR, Allcock RJN, Kresoje N, Laing NG, Thorburn DR, Slama A, Christodoulou J, Rustin P.   (2013)  Mutations in CYC1, Encoding Cytochrome c1 Subunit of Respiratory Chain Complex III, Cause Insulin-Responsive Hyperglycemia.  Am J Hum Genet 93: 384-389

Tucker EJ, Wanschers BFJ, Szklarczyk R, Mountford HS, Wijeyeratne XW, van den Brand MAM, Leenders AM, Rodenburg RJ, Reljić B, Compton AG, Frazier AE, Bruno DL, Christodoulou J, Endo H, Ryan MT, Nijtmans LG, Huynen MA and Thorburn DR. (2013) Mutations in the UQCC1-Interacting Protein, UQCC2, Cause Human Complex III Deficiency Associated with Perturbed Cytochrome b Protein Expression.  PLOS Genet  9:e1004034

Lopes Costa A, Le Bachelier C, Mathieu L, Rotig A, Boneh A, De Lonlay P, Tarnopolsky MA, Thorburn DR, Bastin J and Djouadi F.  (2014)  Beneficial effects of Resveratrol on respiratory chain defects in patients' cells involve ER and ERR-α signalling. Hum Mol Genet  23: 2106-19

Lim SC, Smith KR, Stroud DA, Compton AG, Tucker EJ, Dasvarma A, Gandolfo LC, Marum JE, McKenzie M, Peters HL, Mowat D, Procopis PG, Wilcken B, Christodoulou J, Brown GK, Ryan MT, Bahlo M, Thorburn DR. (2014) A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh Syndrome.   Am J Hum Genet 94: 209-222