Professor David Thorburn
contact details
Professor David Thorburn
Theme Director - Genetic Disorders
Murdoch Childrens Research Institute
Department of Paediatrics, University of Melbourne
Royal Children's Hospital
Flemington Road
Parkville
Victoria, 3052
Australia
T +61 3 8341 6235
E david.thorburn@mcri.edu.au
biography
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 120 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.
achievements
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 - 2012 Invited speaker at 10 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 120 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 250 of these patients
in a total of 8 mtDNA genes, 16 nuclear genes in which mutations
had previously been described and 10 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