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Professor David Thorburn
Professor David Thorburn is co-Group Leader of Brain & Mitchondrial Research at the Murdoch Children's Research Institute.
This group is primarily involved in researching the genetic basis of mitochondrial energy generation disorders. His research contributions include improving diagnostic methods, translating knowledge about mitochondrial DNA genetics into practical reproductive options, defining diagnostic criteria and epidemiology, identifying novel "disease" genes and characterising mouse models and human stem cell models of mitochondrial disease.
His laboratory has acted as the national referral centre for the diagnosis of mitochondrial disease in children for over 20 years and diagnosed more than 700 children. Through studies in-house and with collaborators, his group has identified disease-causing mutations in over 400 of these patients in a total of 11 mtDNA genes, over 50 nuclear genes in which mutations had previously been described and 24 novel nuclear disease genes.
Professor Thorburn received his PhD in Biochemistry from the University of Sydney in 1987 before completing Fulbright and National Health and Medical Research Council 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 and a Fellow and past-President of the Human Genetics Society of Australasia. He is also a Founding Fellow of the Faculty of Science of the Royal College of Pathologists of Australasia and a Fellow of the Australian Academy of Health and Medical Sciences.
Professor Thorburn has published over 180 research papers, including recent papers in Nature, Molecular Cell, Brain and Am J Hum Genet. He supervises postdoctoral Fellows, PhD, MSc and Honours students.
- Honorary Professorial Fellow, Department of Paediatrics, University of Melbourne
- Honorary Fellow, Victorian Clinical Genetic Services
- Board of Directors, the Mito Foundation
2018: Vincent Chiodo Charitable Foundation Fellow
2018: Fellowship of the Australian Academy of Health and Medical Sciences
2018: Faculty of Science Orator, Royal College of Pathologists, Australasia
2012: David Danks Oration, University of Melbourne
2011 - : Founding Fellowship of the Faculty of Science, Royal College of Pathologists, Australasia
2007-2009: President, Human Genetics Society of Australasia
2007: Sutherland Lecturer, Human Genetics Society of Australasia
2012-2018: Invited speaker at 18 international conferences in the fields of Mitochondrial Disease, Inherited Metabolic Disease, Human Genetics, Genetics, Child Neurology, Gastroenterology and Nephrology in Japan, China, Taiwan, Germany, Netherlands, Finland, Turkey, Brazil, USA and Australia.
Professor David Thorburn's research has focused on inherited metabolic disorders, particularly those affecting mitochondrial energy generation, which comprise more than 300 monogenic disorders.
Recent gene identification studies have used "Next Generation" DNA sequencing approaches such as Whole Exome and Whole Genome Sequencing to identify changes in the mitochondrial DNA and in known and novel nuclear genes that may underlie mitochondrial disease in patients and to validate these by functional analyses.
Our bioinformatic 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, with the aim of reducing the need for invasive procedures such as muscle biopsy. A major goal is to translate this study 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. Prof. Thorburn has been a prominant advocate of changing legislation to allow mitochondrial donation (sometimes called 3-person IVF) to enable families to have a child free of mitochondrial DNA disease, which has resulted in a Senate Report outlining a path to enable this approach.
Aside from genetics, Professor Thorburn has substantial involvement in studying cellular and animal models of mitochondrial disorders. These include two 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. Cellular model systems being studied include primary neuronal and astrocyte cell lines from the mouse models plus human stem cell models to study mechanisms and potential treatment approaches.
- Using massively parallel sequencing to improve diagnosis and gene discovery for mitochondrial disorders.
- Cellular Models for mitochondrial disease using primary cell lines, induced pluripotent stem cells and human embryonic stem cells.
Forbes JM and Thorburn DR (2018) Mitochondrial dysfunction in diabetic kidney disease: Climate change or power shortage? Nature Reviews Nephrology 14:291-312
Frazier AE, Thorburn DR and Compton AG (2018) Mitochondrial energy generation disorders: the pathways from genotypes to phenotypes. J Biol Chem (online Dec.12, 2017, doi:10.1074/jbc.R117.809194)
Desai R., Frazier AE, Durigon R, Patel H, Jones AW, Dalla Rosa I, Lake NJ, Compton AG, Mountford HS, Tucker EJ, Mitchell ALR, Jackson D, Sesay A, Di Re M, van den Heuvel LP, Burke D, Francis D, Lunke S, McGillivray G, Mandelstam S, Mochel F, Keren B, Jardel C, Turner AM, Andrews IA, Smeitink J, Spelbrink JN, Heales SJ, Kohda M, Ohtake A, Murayama K, Okazaki Y, Lombes A, Holt IJ, Thorburn DR* and Spinazzola A* (2017) ATAD3 gene cluster deletions cause cerebellar dysfunction associated with altered mitochondrial DNA and cholesterol metabolism. Brain 140: 1595-1610 * Joint corresponding authors
Lake NJ, Webb BD, Stroud DA, Richman TR, Ruzzenente B, Compton AG, Mountford HS, Pulman J, Zangarelli C, Rio M, Bodaert N, Assouline Z, Sherpa MD, Schadt EE, Houten SM, Byrnes J, McCormick EM, Zolkipli-Cunningham Z, Haude K, Zhang Z, Retterer K, Bai R, Calvo SE, Mootha VEK, Christodoulou J, Rötig A, Filipovska A, Cristian I, Falk MJ, Metodiev MD and Thorburn DR (2017) Biallelic mutations in MRPS34 lead to instability of the small mitoribosomal subunit and Leigh syndrome. Am J Hum Genet 101: 239-254
Frazier AE, Holt IJ, Spinazzola A and Thorburn DR (2017) Genotype-phenotype correlation in ATAD3A deletions: not just of scientific relevance. Brain 140: e67
Kang Y, Stroud DA, Baker MJ, De Souza DP, Frazier AE, Liem M, Tull D, Mathivanan S, McConville MJ, Thorburn DR, Ryan MT and Stojanovski D (2017) Sengers syndrome associated mitochondrial acylglycerol kinase, is a subunit of the human TIM22 protein import complex. Molecular Cell 67: 457-470
Stroud DA, Surgenor EE, Formosa LE, Reljic B, Frazier A, Dibley MG, Osellame LD, Stait T, Beilharz TH, Thorburn DR, Salim A and Ryan MT (2016) Accessory subunits are integral for assembly and function of human mitochondrial complex I. Nature 538: 123–126
Lake NJ, Compton AG, Rahman S and Thorburn DR (2016) Leigh Syndrome: One disorder, more than 75 monogenic causes. Ann Neurol 79: 190-203
Alston CL, Compton AG, Formosa LE, Strecker V, Oláhová M, Haack TB, Smet J, Stouffs k, Diakumis P, Ciara E, Cassiman D, Romain N, Yarham JW, HeL, De Paepe B, Vanlander AV, Seneca S, Feichtinger RG, Płoski R, Rokicki D, Pronicka E, Haller RG, Van Hove JLK, Bahlo M, Mayr JA, Van Coster R, Prokisch H, Wittig I, Ryan MT, Thorburn DR* and Taylor RW* (2016) Biallelic mutations in TMEM126B cause severe complex I deficiency with a variable clinical phenotype. Am J Hum Genet 99:217-27 * Joint Corresponding Authors
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 and 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 * Joint Corresponding Authors
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 and 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 and 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
Pfeffer G, Majamaa K, Turnbull DM, Thorburn D and Chinnery PF (2012) Treatment for mitochondrial disorders. Cochrane Db Syst Rev 4:CD004426
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. Sci Transl Med 4, 118ra10
* Joint Corresponding Authors
Riley LG, Cooper S, Hickey P, Rudinger-Thirion J, McKenzie M, Compton A, Lim SZ, Thorburn DR, Ryan MT, Giegé R, Bahlo M and 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
* Joint Corresponding Authors
Tucker EJ, Hershman SG, Köhrer K, Belcher-Timme CA, Patel J, Goldberger OA, Christodoulou J, Silberstein JM, McKenzie M, Ryan MT, Compton AG, Jaffe JD, 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 Metab 14:428-434 * Joint Corresponding Authors
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
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: 468-47
- National Health & Medical Research Council
- USA Department of Defense Congressionally Directed Medical Research Program
- Mito Foundation
- Vincent Chiodo Charitable Trust