A/Professor Paul Lockhart
Associate Professor Paul Lockhart is the Group Leader of Neurogenetic Research at the Murdoch Childrens Research Institute.
He is currently the National Health and Medical Research Council (NHMRC) Career Development Fellow and leads a research group that investigates the molecular basis of neurogenetic disorders.
Paul received his PhD in Genetics (Title: Molecular analysis of copper transport in sheep) from the University of Melbourne in 2000. He was awarded a NHMRC CJ Martin Fellowship to study the genetics of neurodegenerative disorders, specifically Parkinson's disease, with Professor John Hardy (2000-2001) and Professor Matthew Farrer (2002-2003) at The Mayo Clinic, Florida. He returned to Australia in 2004 and joined the newly formed Bruce Lefroy Centre (BLC) at Murdoch Childrens, with the aim of establishing a laboratory research group to complement the clinical and public health research activities of the BLC. He received a NHMRC RD Wright Fellowship in 2005 and was appointed Co-Director of the BLC in 2009.
- Co-Director, Department of Genetics, Bruce Lefroy Centre
- Associate Professor, Department of Paediatrics, University of Melbourne
- Career Development Award (II), NHMRC, 2012-2015
- Early Career Prize, International Skeletal Dysplasia Society, 2010
- AW Campbell Award, Australian Neuroscience Society, 2008
- Rising Star, MCRI, 2007
- RD Wright Fellow, NHMRC, 2005-2009
The identification and characterisation of genes underlying Mendelian disorders has been responsible for the rapid advances in our understanding of human disease over the last 20 years, and has considerable impact on our understanding of complex common diseases that are currently considered to be idiopathic.
Recent advances in genetic technologies mean we now have the ability to sequence entire exomes and genomes in a rapid and cost effective manner. This means gene discovery can now be effectively performed in families with few affected individuals and sib-pairs, both previously underpowered for such analysis. Indeed, we are rapidly approaching the point where whole exome/genome sequencing of individuals will be a cost-effective method for diagnosis of many disorders. These genome sequence datasets have enormous potential for application in the rapidly developing field of personalised medicine. These advances have particular relevance to disorders of the brain, which is a specific area of research interest.
In Australia, brain and mind disorders collectively are one of the largest and fastest growing disease burdens. Affecting both the young and the elderly, these disorders are typically chronic and debilitating with a large economic cost to individuals and the community. A current focus of the laboratory is to apply new genomic technologies and capacity to neurogenetic disorders that have previously proven intractable to genetic analysis. The laboratory works very closely with the clinical services of Genetic Health Services Victoria and the Royal Children's Hospital. Once novel disease-associated genes are identified, we perform molecular studies in cell and animal models to determine the function of the encoded protein and investigate the underlying pathogenesis of disease. In addition to the immediate counselling and clinical benefit to affected patients and families, this research is essential for the development of treatment programs and prevention or onset-delay strategies for brain and mind disorders.
1. Accelerated Gene Identification Program (AGIP)
2. Understanding the molecular basis of Parkinson’s disease
3. Clinical and Molecular Genetic Study of Autism Spectrum Disorders
4. Understanding the cause of brain malformations.
Sim JC, Scerri T, Fanjul-Fernández M, Riseley JR, Gillies G, Pope K, van Roozendaal H, Heng JI, Mandelstam SA, McGillivray G, MacGregor D, Kannan L, Maixner W, Harvey AS, Amor DJ, Delatycki MB, Crino PB, Bahlo M, Lockhart PJ*, Leventer RJ*. Familial cortical dysplasia caused by mutation in the mTOR regulator NPRL3
Ann Neurol. 2015 Aug 18. doi: 10.1002/ana.24502. [Epub ahead of print]
* = joint senior and corresponding authors
Leventer RJ, Scerri T, Marsh AP, Pope K, Gillies G, Maixner W, MacGregor D, Harvey AS, Delatycki MB, Amor DJ, Crino P, Bahlo M, Lockhart PJ. Hemispheric cortical dysplasia secondary to a mosaic somatic mutation in MTOR
Neurology. 2015 May 19;84(20):2029-32.
Wilson GR, Sim JC, McLean C, Giannandrea M, Galea CA, Riseley JR, Stephenson SE, Fitzpatrick E, Haas SA, Pope K, Hogan KJ, Gregg RG, Bromhead CJ, Wargowski DS, Lawrence CH, James PA, Churchyard A, Gao Y, Phelan DG, Gillies G, Salce N, Stanford L, Marsh AP, Mignogna ML, Hayflick SJ, Leventer RJ, Delatycki MB, Mellick GD, Kalscheuer VM, D'Adamo P, Bahlo M, Amor DJ, Lockhart PJ. Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with a-synuclein pathology
Am J Hum Genet. 2014 Dec 4;95(6):729-35.
Lessel D*, Vaz B*, Halder S*, Lockhart PJ*, Marinovic-Terzic I*, Lopez-Mosqueda J, Philipp M, Sim JC, Smith KR, Oehler J, Cabrera E, Freire R, Pope K, Nahid A, Norris F, Leventer RJ, Delatycki MB, Barbi G, von Ameln S, Högel J, Degoricija M, Fertig R, Burkhalter MD, Hofmann K, Thiele H, Altmüller J, Nürnberg G, Nürnberg P, Bahlo M, Martin GM, Aalfs CM, Oshima J, Terzic J, Amor DJ, Dikic I, Ramadan K, Kubisch C. Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features
Nat Genet. 2014 Nov;46(11):1239-44.
* = joint first authors
Coe BP, Witherspoon K, Rosenfeld JA, van Bon BW, Vulto-van Silfhout AT, Bosco P, Friend KL, Baker C, Buono S, Vissers LE, Schuurs-Hoeijmakers JH, Hoischen A, Pfundt R, Krumm N, Carvill GL, Li D, Amaral D, Brown N, Lockhart PJ, Scheffer IE, Alberti A, Shaw M, Pettinato R, Tervo R, de Leeuw N, Reijnders MR, Torchia BS, Peeters H, O'Roak BJ, Fichera M, Hehir-Kwa JY, Shendure J, Mefford HC, Haan E, Gécz J, de Vries BB, Romano C, Eichler EE. Refining analyses of copy number variation identifies specific genes associated with developmental delay
Nat Genet. 2014 Oct;46(10):1063-71.
Wilson GR, Sunley J, Smith KR, Pope K, Bromhead CJ, Fitzpatrick E, Di Rocco M, van Steensel M, Coman DJ, Leventer RJ, Delatycki MB, Amor DJ, Bahlo M, Lockhart PJ. Mutations in SH3PXD2B cause Borrone dermato-cardio-skeletal syndrome
Eur J Hum Genet. 2014 Jun;22(6):741-7
Sim JC, White SM, Fitzpatrick E, Wilson GR, Gillies G, Pope K, Mountford HS, Torring PM, McKee S, Vulto-van Silfhout AT, Jhangiani SM, Muzny DM, Leventer RJ, Delatycki MB, Amor DJ, Lockhart PJ.
Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency
Orphanet J Rare Dis. 2014 Mar 27;9:43.
Mill P*, Lockhart PJ*, Fitzpatrick E, Mountford HS, Hall EA, Reijns MA, Keighren M, Bahlo M, Bromhead CJ, Budd P, Aftimos S, Delatycki MB, Savarirayan R, Jackson IJ, Amor DJ.
Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis
Am J Hum Genet. 2011 Apr 8;88(4):508-15
* = joint first and corresponding authors
Chartier-Harlin MC, Dachsel JC, Vilarino-Guell C, Lincoln SJ, Lepretre F, Hulihan MM, Kachergus J, Milnerwood AJ, Tapia L, Song MS, Le Rhun E, Mutez E, Larvor L, Duflot A, Vanbesien-Mailliot C, Kreisler A, Ross OA, Nishioka K, Soto-Ortolaza AI, Cobb SA, Melrose HL, Behrouz B, Keeling BH, Bacon JA, Hentati E, Williams L, Yanagiya A, Sonenberg N, Lockhart PJ, Zubair AC, Uitti RJ, Aasly JO, Krygowska-Wajs A, Opala G, Wszolek ZK, Frigerio R, Maraganore DM, Gosal D, Lynch T, Hutchinson M, Bentivoglio AR, Valente EM, Nichols WC, Pankratz N, Foroud T, Gibson RA, Hentati F, Dickson DW, Destee A, Farrer MJ.
Translation initiator EIF4G1 mutations in familial Parkinson disease
Am J Hum Genet 2011 Sep 9;89(3):398-406.
Wilson GR, Wang HX, Egan GF, Robinson PJ, Delatycki MB, O'Bryan MK, Lockhart PJ. Deletion of the Parkin co-regulated gene causes defects in ependymal ciliary motility and hydrocephalus in the quakingviable mutant mouse
Hum Mol Genet 2010 Apr 15;19(8):1593-602.
- NHMRC Project grant 1098255, 2016-2020, Understanding the Neurobiology of Autism Spectrum Disorder (CIs: Scheffer, Lockhart, Delatycki, Wilson, Fanjul, Stanley)
- NHMRC Project grant 1102207, 2016-2018, A randomised placebo-controlled crossover trial of micronised resveratrol as a treatment for Friedreich ataxia (CIs: Delatycki, Yiu, Corben, Cranswick, Lockhart, Wilmot, Lamont, O’Sullivan)
- NHMRC Project grant 1059666, 2014-2016, Determining the genetic control of Corpus Callosum development (CIs: Lockhart, Leventer, Amor, Delatycki)
- Brain Foundation Australia grant, 2016, Using brain tissue to find the causes of epilepsy (CIs: Leventer, Lockhart)
- Campbell Edwards Trust, 2015-2016, Understanding brain malformations in childhood (CIs: Leventer, Lockhart)
- NHMRC Project grant 1041860, 2013-2015, Functional characterisation of a new gene for Parkinson's disease (CIs: Lockhart, Mellick, Amor, Delatycki)
- NHMRC Project grant 1044175, 2013-2015, Genetics of Autism (CIs: Scheffer, Lockhart, Delatycki, Wilson)
- NHMRC Project grant 1046206, 2013-2015, Functional analysis of protein turnover pathways (CIs: Lockhart, Farrer)
- APA Postgraduate scholarship, 2013-2015 (Marsh)