Neurodevelopmental Genomics Research

Research Overview

Under the campus partnership, our research is embedded in MCRI.  Full research profile may be found at https://www.mcri.edu.au/research/themes/genetics/neurodevelopmental-genomics.

The Neurodevelopmental Genomics Research Group is dedicated to identifying disease genes that affect the normal development and function of the brain and neuronal cells. By studying the functions of these genes we hope to gain a better understanding of the biology of these neurodevelopmental disorders.  In collaboration with senior clinical and laboratory colleagues of the Victorian Clinical Genetics Services we have established the Undiagnosed Diseases Program Victoria (UPD-Vic), which is focussed on using next generation sequencing and functional analyses to “solve the unsolved”, paediatric onset complex disorders that are strongly suspected to have a monogenic basis.

One particular area of our research focus is Rett syndrome and related disorders.  Rett syndrome is the second most common cause of severe intellectual disability in females (after Down syndrome).  We suspect that yet unidentified gene mutations are involved in Rett syndrome patients where a genetic diagnosis has not been made. Recent developments in DNA sequencing technology may allow us to discover new genes not previously associated with Rett syndrome. To model Rett syndrome ‘in a dish’ we are using Induced pluripotent stem cell (iPSC) technology where we can turn patient skin cells into different cell types relevant to Rett syndrome. This will allow us to better study the consequences of mistakes identified in these Rett syndrome genes, and provide patient-specific models for high-throughput therapeutic development.

We are also focusing on developing early diagnosis and intervention tests for this rare genetic disease. There are still no robust biochemical markers of Rett syndrome, but by using high throughput screening techniques on patient samples (blood and urine) we hope to identify protein or other chemical markers that detect Rett syndrome. Such biomarkers have the potential to be used by clinicians as an early screening test for Rett syndrome.

Finally, working with Professor David Thorburn and his Mitochondrial Research Group, we are actively involved in the identification and functional characterisation of new mitochondrial disease genes.

Staff

  • Dr Ken Pang, Consultant Paediatrician
  • Dr Nicole van Bergen, Research Officer
  • Dr Rocio Ruis, PhD Candidate
  • Ms Simran Kaur, PhD Candidate
  • Ms Marilou Barrios, PhD Candidate
  • Mr Blake Smith, PhD Candidate
  • Ms Lucy Liu, MA Candidate

Collaborators

  • Metabolic Research Group – Kids Research Institute, Sydney Children’s Hospitals Network
  • Professor Carolyn Sue – Kolling Research Institute, Sydney
  • Professor David Ravine – School of Pathology and Laboratory Medicine, University of Perth
  • Professor Helen Leonard – Telethon Kids Institute, Perth
  • Dr Yiran Guo and Dr Brendan Keating – Center for Advanced Genomics, Children’s Hospital of Philadelphia
  • Dr Carole Lister, Luxembourg Centre for Systems Biomedicine, Universite du Luxembourg

Research Publications

  • Tong, JHS; Hawi, Z; Dark, C; Cummins, TD; Johnson, BP; Newman, DP; Lau, R; Vance, A; Heussler, HS; Matthews, N; Bellgrove, MA; Pang, "KC Separating the wheat from the chaff: systematic identification of functionally relevant noncoding variants in ADHD" MOLECULAR PSYCHIATRY
  • May, T., Pang, K., Williams, K.J. "Gender variance in children and adolescents with autism spectrum disorder from the National Database for Autism Research" INTERNATIONAL JOURNAL OF TRANSGENDERISM
  • Heimer, G; Keratar, JM; Riley, LG; Balasubramaniam, S; Eyal, E; Pietikainen, LP; Hiltunen, JK; Marek-Yagel, D; Hamada, J; Gregory, A; Rogers, C; Hogarth, P; Nance, MA; Shalva, N; Veber, A; Tzadok, M; Nissenkorn, A; Tonduti, D; Renaldo, F; Kraoua, I; Panteghini, C; Valletta, L; Garavaglia, B; Cowley, MJ; Gayevskiy, V; Roscioli, T; Silberstein, JM; Hoffmann, C; Raas-Rothschild, A; Tiranti, V; Anikster, Y; Christodoulou, J; Kastaniotis, AJ; Ben-Zeev, B; Hayflick, SJ "MECR Mutations Cause Childhood-Onset Dystonia and Optic Atrophy, a Mitochondrial Fatty Acid Synthesis Disorder" AMERICAN JOURNAL OF HUMAN GENETICS
  • Balasubramaniam, S; Lewis, B; Dock, M; Said, HM; Tarailo-Graovac, M; Mattman, A; van Karneebek, CD; Thorburn, DR; Rodenburg, RJ; Christodoulou "Leigh-like syndrome due to homoplasmic m.8993T>G variant with hypocitrullinemia and unusual biochemical features suggestive of multiple carboxylase deficiency (MCD)" JIMD REPORTS
  • Nguyen TA, Pang KC, Masters SL. "Intercellular communication for innate immunity" Molecular Immunology
  • Riley LG, Cowley MJ, Gayevskiy V, Roscioli T, Thorburn DR, Prelog K, Bahlo M, Sue CM, Balasubramaniam S, Christodoulou J. "A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders." J Inher Metab Dis. 2016 November; 39(6): doi 10.1007/s10545-016-0010-6  
  • Riley LG, Cowley MJ, Gayevskiy V, Roscioli T, Thorburn DR, Prelog K, Bahlo M, Sue CM, Balasubramaniam S, Christodoulou J "A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders." J Inherit Metab Dis. 2016 Dec 19. [Epub ahead of print]
  • Heimer G, Kerätär HM, Riley JG, Balasubramaniam S,Pietikäinen LP, Hiltunen JK, Eyal E, Marek-Yagel D, Hamada J, Gregory A, Rogers C, Hogarth P, Nance M, Shalva N, Veber A, Elpeleg O, Tonduti D, Renaldo F, Kraoua I, Panteghini C, Valletta L, Garavaglia B, Cowley MJ, Gayevskiy V, Roscioli T, Silberstein JM, Raas-Rothschild A, Tiranti V, Anikster Y, Christodoulou J, Kastaniotis AJ, Ben-Zeev B,Hayflick SJ. "MECR mutations cause childhood onset dystonia and optic atrophy – a mitochondrial fatty acid synthesis disorder." Amer J Hum Genet, 2016; 99(6); 1229-1244.
  • Heimer G, Kerätär JM, Riley LG, Balasubramaniam S, Eyal E, Pietikäinen LP, Hiltunen JK, Marek-Yagel D, Hamada J, Gregory A, Rogers C, Hogarth P, Nance MA, Shalva N, Veber A, Tzadok M, Nissenkorn A, Tonduti D, Renaldo F; Kraoua I, Panteghini C, Valletta L, Garavaglia B, Cowley MJ, Gayevskiy V, Roscioli T, Silberstein JM, Hoffmann C, Raas-Rothschild A, Tiranti V, Anikster Y, Christodoulou J, Kastaniotis AJ, Ben-Zeev B, Hayflick SJ "MECR Mutations Cause Childhood-Onset Dystonia and Optic Atrophy, a Mitochondrial Fatty Acid Synthesis Disorder" Am J Hum Genet. 2016 Dec 1;99(6):1229-1244. doi: 10.1016/j.ajhg.2016.09.021. Epub 2016 Nov 3
  • Fehr S, Wong K, Chin R, Williams S, de Klerk N, Forbes D, Krishnaraj R, Christodoulou J, Downs J, Leonard H. "Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder." Neurology.  2016: 87(21); 2206-2213
  • Fehr S, Wong K, Chin R, Williams S, de Klerk N, Forbes D, Krishnaraj R, Christodoulou J, Downs J, Leonard H "Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder" Neurology. 2016 Nov 22;87(21):2206-2213. Epub 2016 Oct 21.
  • Alodaib A, Sobreira N, Gold WA, Riley LG, Van Bergen NJ, Wilson MJ, Bennetts B, Thorburn DR, Boehm C, Christodoulou J. Whole exome sequencing identifies novel variants in PNPT1 causing oxidative phosphorylation defects and severe multisystem disease. Eur J Hum Genet. 2016: 25(1); 79-84.
  • Alodaib A, Sobreira N, Gold WA, Riley LG, Van Bergen NJ, Wilson MJ, Bennetts B, Thorburn DR, Boehm C, Christodoulou J "Whole-exome sequencing identifies novel variants in PNPT1 causing oxidative phosphorylation defects and severe multisystem disease." Eur J Hum Genet. 2016 Jan;25(1):79-84. doi: 10.1038/ejhg.2016.128. Epub 2016 Oct 19.
  • Balasubramaniam S, Lewis B, Mock DM, Said HM, Tarailo-Graovac M, Mattman A, van Karneebek CD, Thorburn DR, Rodenburg RJ, Christodoulou J. "Leigh-like syndrome due to homoplasmic m.8993T>G variant with hypocitrullinemia and unusual biochemical features suggestive of multiple carboxylase deficiency" (MCD). J Inher Metab Dis Reports 22nd July 2016. PMID: 27450367 DOI: 10.1007/8904_2016_559
  • Balasubramaniam S, Lewis B, Mock DM, Said HM, Tarailo-Graovac M, Mattman A, van Karneebek CD, Thorburn DR, Rodenburg RJ, Christodoulou J "Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)." JIMD Rep. 2016 Jul 22. [Epub ahead of print]

Research Projects



Faculty Research Themes

Child Health

School Research Themes

Child Health in Medicine, Neuroscience & Psychiatry



Key Contact

For further information about this research, please contact Professor John Christodoulou

Department / Centre

Paediatrics

Unit / Centre

Neurodevelopmental Genomics Research