Professor David Thorburn
Professor David Thorburn is the Theme Director of Genetics and Group Leader of Mitchondrial Research at the Murdoch Childrens Research Institute.
His 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 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 500 children. Through studies in-house and with collaborators, his group has identified disease-causing mutations in over 280 of these patients in a total of eight mtDNA genes, 25 nuclear genes in which mutations had previously been described and 16 novel nuclear disease genes, including five of the nine known Complex I assembly defect 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 and Principal Examiner in Genetics of the Faculty of Science of the Royal College of Pathologists of Australasia.
Professor Thorburn 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.
- Theme Director, Genetics, Murdoch Childrens Research Institute
- Group Leader, Mitochondrial Research, Genetics, Murdoch Childrens Research Institute
- Honorary Professorial Fellow, Department of Paediatrics, University of Melbourne
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 16 international conferences in the fields of Mitochondrial Disease, Inherited Metabolic Diseases, Child Neurology, Gastroenterology and Nephrology in China, Finland, Japan, Netherlands, Norway, Taiwan, USA and Australia
Professor David Thorburn's research has focused on inherited metabolic disorders, particularly those affecting mitochondrial energy generation, which comprise more than 160 monogenic disorders.
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 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.
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 astrocytes cell lines from the mouse models plus human embryonic stem cells.
- Using massively parallel sequencing to improve diagnosis and gene discovery for mitochondrial disorders.
- Mouse models for mitochondrial disease: understanding pathogenesis and improving treatment strategies.
- Cellular Models for mitochondrial disease using primary cell lines, induced pluripotent cells and human embryonic stem cells.
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
Tucker EJ, Wanschers BFJ, Szklarczyk R, Mountford HS, Wijeyeratne XW, van den Brand MAM, Leenders AM, Rodenburg RJ, Reljic 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
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
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 Med 4: 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 USA 109:6165-6170
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
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, 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
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