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Professor John Christodoulou
John Christodoulou is a medical graduate of the University of Sydney, and has formal qualifications in paediatrics, medical genetics and genetic pathology, with his main focus of clinical practice being in the diagnosis and management of children with inborn errors of metabolism for over three decades. He has an active laboratory-based Rett syndrome research program, as well as in genetic metabolic disorders, including phenylketonuria (PKU) and the mitochondrial respiratory chain (energy production) disorders, and has a strong research interest in the application of next generation sequencing technologies for disease gene discovery in rare Mendelian disorders. He was the Director of the Western Sydney Genetics Program at the Children's Hospital at Westmead, and the Head of the Discipline of Genetic Medicine at Sydney University until December 2015. In January of 2016 he took up the inaugural Chair of Genomic Medicine at the Murdoch Childrens Research Institute and the University of Melbourne, and 2017 became the Director of the Genetics Research Theme at the MCRI.
John is a former President of the Human Genetics Society of Australasia (2005-2007).
- National Health and Medical Research Council of Australia Postgraduate Medical Research Fellowship -1987-1990.
- American Society of Human Genetics Postdoctoral Clinical Research Student Award, 1992.
- Vice-Chancellor's Award for Excellence in Postgraduate Research Higher Degree Supervision, 2004.
- Became a Member of the Order of Australia (AM), January 2010. Awarded in recognition of my contributions to genetic practice and research, particularly in the area of genetic metabolic disorders.
- Ippokratis Award for outstanding achievement by a medical professional. Awarded by the Australasian Hellenic Educational Progressive Association (AHEPA), March 2010.
- Elected as Fellow of the Australian Academy of Health & Medical Sciences – October 2017
Professor Christodoulou has made significant contributions to the field of mitochondrial respiratory chain disorders research include contribution to the discovery over a dozen new disease genes, one of which led to the establishment of a specific therapy (riboflavin) as being very effective. In addition, he has delineated and expanded the phenotypes of a number of mitochondrial disorders and has been involved in the development of a number of new methods, including automation of respiratory chain enzyme analysis, exploration of FACS in the diagnosis of mitochondrial disorders, development of DHPLC for screening mtDNA for mutations, and the use of cybrid technology to delineate the underlying genetic basis of mitochondrial disorders. With collaborators he also identified a naturally occurring dog model of Leigh disease, the genetic basis of which is yet to be established.
Professor Christodoulou has also made significant contributions to the field of RTT research include the development of a highly regarded web-based locus specific MECP2 mutation database, and which has been awarded continuous funding since 2006 from the US-based International Rett Syndrome Foundation. In collaboration with national and international colleagues he has contributed to the careful delineation of the natural history and phenotype-genotype correlations in RTT. Using several RTT mouse models and cell culture approaches using cell lines derived from patients with MECP2 mutations, he has gained further insights into to understanding the pathogenesis of RTT, including ground breaking identification of the first genetic and environmental modifiers of disease severity. His group discovered a new gene, cyclin dependent kinase-like 5 (CDKL5), causing an atypical form of RTT, which has led to a new direction of research into RTT and related disorders. They also identified a novel CDKL5 isoform as the major isoform in brain, necessitating a change in the approach to genetic testing for the CDKL5 disorder.
More recently, a major focus of his research has been the use of next generation sequencing (NGS) technologies for gene discovery in rare Mendelian disorders, and as co-lead of the Australian Genomics Health Alliance he is evaluating the prospects for the introduction of next generation sequencing into the Australian healthcare system.
- The Biology of Rett Syndrome: MECP2 Mutations and Beyond
- The Molecular Pathogenesis of Mitochondrial Respiratory Chain Disorders
- Application of Next Generation Sequencing Technologies for Mendelian Gene Disorder Discoveries
- Genetically Engineered Probiotics for the Treatment of Human Disease: Phenylketonuria as a Model Disease
- Preparing Australia for Genomic Medicine: A Proposal by the Australian Genomics Health Alliance
1. Gold WA, Krishnaraj R, Ellaway C, Christodoulou J. Rett syndrome: A genetic update and clinical review focusing on comorbidities. ACS Chem Neurosci 2018: 9(2); 167-176
2. Nafisinia M, Menezes MJ, ... Christodoulou J.Tread carefully: A functional variant in the human NADPH Oxidase 4 (NOX4) is not disease causing. Mol Genet Metab 2018: 123(3); 382-387
3. Larson AA, Balasubramaniam S, Christodoulou J, ... Weisfeld-Adams J. Biochemicalsignatures of multiple carboxylase deficiency in children with mutations in MT-ATP6. Mitochondrion 2018: pii: S1567-7249(17)30089-2
4. Wong K, Downs J, ...Christodoulou J, Elliott E, Leonard H. Impact of gastrostomy placement on nutrional status, physical health and parental well-being of females with Rett syndrome: A longitudinal study of an Australian population. J Pediatr. 2018 Sep;200:188-195.
5. Kothur K, Holman K, ... Christodoulou J, Gill D, Bennetts B.The Diagnostic Yield of Targeted Massively Parallel Sequencing in Children with Epileptic Encephalopathy. Seizure: 2018: 59:132-140
6. Coman D, Vissers LELM, ...Christodoulou J, Wevers RA, Pitt J. Squalene synthase deficiency; clinical, biochemical and molecular characterization of a defect of cholesterol biosynthesis. Amer J Hum Genet 2018: 103(1); 125-130.
7. McMillan HJ, Telegrafi A, ... Christodoulou J, ...Yoon G. Recessive mutations in ATP8A2 cause severe hyptonia, cognitive impairment, hyperkinetic movement disorders and progressive optic atrophy. Orphanet J Rare Dis 2018: 13; 86
8. Riley LG, Heeney MM, ... Christodoulou J, Fleming MD. The phenotypic spectrum of gerline YARS2variants: from isolated siderblastic anemia to mitochondrial myopathy, lactic acidosis and sideroblastic anemia 2. Haematologica. 2018 Jul 19. pii: haematol.2017.182659. doi: 10.3324/haematol.2017.182659
1. Shahen VA, Cantrill LC, Sangani NB, Christodoulou J, Gold WA. A simple and efficient ImageJ macro toolset for analysing mitochondrial trafficking in neuronal cells. Acta Histochem. 2018 Nov;120(8):797-805. doi: 10.1016/j.acthis.2018.09.001. Epub 2018 Sep 14.
2. Morales-Briceño H, Chang F, ...Christodoulou J (co-senior author), Fung SCV(co-senior author). Paroxysmal dyskinesias with drowsiness and bilateral thalamic lesions in GABA transaminase deficiency. Accepted by Neurology 2ndOctober 2018
3. Van Bergen N, Guo Y, ... Christodoulou J (co-senior author), Linster C, Ellard S, Hakonarson H. NAD(P)HX Dehydratase (NAXD) deficiency: a novel neurodegenerative disorder exacerbated by febrile illnesses. Accepted by Brain 17thOctober 2018
4. Van der Knaap MS, Bugiani M, ...Christodoulou J, Simons C, Salomons GS, Mochel F. Bi-allelic mutations in LARS2and KARS(2)cause deafness and (ovario)leukodystrophy with mitochondrial signature. Accepted Neurology 6thNovember 2018
5. Schonewolf-Greulich B, Bisgaard M-M, ... Christodoulou J, Fagerberg CR, Tumer Z. Mosaic MECP2 variants in males with classical Rett syndrome features, including stereotypic hand movements. Clin Genet. 2018 Nov 11. doi: 10.1111/cge.13473. [Epub ahead of print]
6. Rius R, Riley LG, ...Christodoulou J.Cryptic intronic NBASvariant reveals the genetic basis of recurrent liver failure in a child. Accepted by the Molecular Genetics and Metabolisam on 6thDecember, 2018.
7. Balasubramaniam S, Christodoulou J, Rahman S. Disorders of riboflavin metabolism. Accepted by J Inher Metab Dis 17 December 2018
8. Costain G, Callewaert B, ... Christodoulou J, ... Meyn M S. De novo missense variants in RAC3 cause a novel neurodevelopmental syndrome. Genet Med. 2018 Oct 8. doi: 10.1038/s41436-018-0323-y.
International Rett Syndrome Foundation Database Grant #2242 – 2014 – 2018
RettBASE: IRSF MECP2 Variation Database – a Global Resource
J. Christodoulou (CIA)
United Mitochondrial Diseases Foundation Grant – 2015 – 2016
Utility of FGF21 and GDF15 as Diagnostic and Prognostic Biomarkers of Mitochondrial Respiratory Chain Disorders
J. Christodoulou (CIA)
NHMRC Targeted Research Grant APP1113531 – 2016 – 2020
Preparing Australia for Genomic Medicine – A proposal by the Australian Genomics Health Alliance
J Christodoulou (CI)
NHMRC CRE APP1117394 – 2016-2021
Transforming the Diagnosis and Management of Severe Neurocognitive Disorders through Genomics
J Christodoulou (CIH)
RCH Foundation Grant 2018 – 2020
Acute Care Genomics – ultra rapid genomic diagnostics for the sickest children
J Christodoulou (CIC)
NHMRC – MRFF Scheme Research Grant Application APP1146756 2017 - 2020
A randomised placebo-controlled trial of combined mitochondrial agents for the treatment of fatigue and depression in multiple sclerosis with an assessment of the impact on kynurenine pathway metabolomics
J Christodoulou CIJ
US Department of Defense office of the Congressionally Directed Medical Research Programs (CDMRP) PR170396 2017 – 2020
Solving the unsolved. Integrating functional, computational and Omic approaches to enable genomic diagnosis of virtually all patients with mitochondrial disease.
NHMRC Project Grant APP116447 2019 -2021
Identifying Novel Genes and Novel Mechanisms of Mitochondrial Diseases: a Multi-Omics Approach
John Christodoulou (CIB)
The Financial Markets Foundation for Children 2017 - 2019
Brain cells in a dish: strategies for novel therapeutics in CDKL5 disorder
John Christodoulou (CIB)