Christodoulou, John

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MB BS 1981 PhD (Melb) FRACP

John Christodoulou has led the world in identifying the underlying biological and genetic causes of Rett syndrome.

Born in Sydney in 1958, John obtained his medical degree at the University of Sydney in 1981. He completed his residency at the Royal Alexandra Children’s Hospital, after which he moved to Melbourne to finish his training in paediatrics. He also undertook specialist training in clinical genetics, completing his PhD in the field of genetic metabolic disorders at the University of Melbourne in 1991. In 1990, he relocated to the Hospital for Sick Children in Toronto, Canada, where he gained further clinical and postdoctoral research experience in genetic metabolic disorders.

John returned to Sydney in 1992, to take up the position of Senior Lecturer in the Department of Paediatrics and Child Health at the University of Sydney and the Royal Alexandra Hospital of Children. From 1994 to 1995, he was Acting Head of the Department of Genetics at the Hospital, also becoming Head of the PKU clinic in 1995. A year later, he was awarded the title of Associate Professor and became the Director of the Western Sydney Genetics Program, the only fully integrated genetics service in NSW.

John’s research focuses on understanding the genetic basis of disorders that affect the brain. Of his research into Rett syndrome, he says:

Rett syndrome is one of the most devastating disorders I have encountered. Our research is aimed at isolating the gene or genes responsible for this tragic disorder. It is only then that we stand any chance of understanding its biological basis, and of designing effective treatments.

Rett syndrome is the second most common (after Down syndrome) cause of severe intellectual disability in females. Recently, mutations in the methyl CpG-binding protein 2 (MECP2) have been identified in most, but not all, females with Rett syndrome. In addition, the clinical phenotype of MECP2 mutations has been expanded to include females with nonspecific intellectual disability of a lesser severity, males with severe neonatal encephalopathy, and pedigrees showing an X-linked pattern of inheritance for intellectual disability. The pathogenesis of MECP2 mutation, however, remains to be established. A group of researchers led by John is investigating the phenotype-genotype correlations in Rett syndrome, using a well characterised sample group of over 130 females with Rett syndrome. In conjunction with other studies, this work should allow identification of the key components contributing to the pathogenesis of Rett syndrome, and may ultimately allow the design of targeted therapies for this currently untreatable disorder.

At present, John and his team are also investigating genetically engineered probiotics as a treatment of human disease. One such disease, Phenylketonuria (PKU), is due to phenylalanine hydroxylase deficiency and, if untreated, results in profound intellectual disability, seizures and aggressive behaviour. Treatment consists of a life-long diet, restricting phenylalanine intake. The diet, however, is unpalatable, and for a number of reasons, compliance tends to deteriorate with age. A group led by John, in collaboration with Dr Ian Alexander of the Gene Therapy Research Unit, Dr Ted O’Loughlin of the Gastroenterology Research Unit (both at the Children’s Hospital at Westmead), and Professor Peter Pouwells of the TNO Nutrition and Food Research Institute in the Netherlands, is developing a novel therapy for treating PKU. This will involve genetically engineering harmless Lactobacillus bacteria to produce an alternate phenylalanine-metabolising enzyme, phenylalanine ammonia-lyase. These engineered organisms, if given orally (as a ‘Yakhult’ type preparation), should metabolise phenylalanine in the small intestine, preventing blood levels from rising. If successful, this novel form of treatment could be translated to other human diseases, and could have wide applicability in the animal husbandry industry.

John has been very active in his various appointments at the University of Sydney and as a member of numerous Faculty of Medicine committees. Since 2000, he has been Chair of the Combined Boards of Postgraduate Studies in the College of Health Sciences, and been a Member of the PhD Awards Subcommittee and the Graduate Studies Committee. He has also been a Member of the Faculty of Medicine Education Committee and the Combined Degree Program Committee since 2001. John became Associate Dean (Postgraduate Studies) of the Faculties of Dentistry, Medicine and Pharmacy in 2002, and was appointed Professor of Paediatrics and Child Health in 2004.

Heavily involved in the professional community, John has been a member of several genetics organisations. From 1997 to 1999 he was President of the NSW branch of the Human Genetics Society of Australasia, becoming President of the national body in 2005. That same year, he was elected to the International Scientific Advisory Committee of the Cyprus Institute of Neurology and Genetics.

John remains Professor in the Discipline of Paediatrics and Child Health.

Citation: Mellor, Lise (2008) Christodoulou, John. Faculty of Medicine Online Museum and Archive, University of Sydney.

An alternate version appears in: Mellor, L. 150 Years, 150 Firsts: The People of the Faculty of Medicine (2006) Sydney, Sydney University Press.