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Dr Sarah Stephenson
Dr Stephenson is a molecular biologist and team leader within the Neurogenetics group at MCRI. Sarah has expertise in using advanced genomic technologies including targeted deep sequencing and high throughput single cell RNAseq to study malformation of brain development (MBD).
MBD are relatively common and are a heavy burden for families, as affected individuals often require lifelong multidisciplinary care from health and community services. There are over 100 new patients seen every year at the Royal Children's Hospital in Melbourne.
Her research aims to understand the developmental process underlying lesion formation and their potent intrinsic ability to cause seizures that suddenly switch on and off and are largely drug resistant. Ultimately Sarah's goal is to identify and develop targeted medical therapies for paediatric brain disorders to then take back to the patient in the form of clinical trials.
To better understand and treat MBD, Dr Stephenson and her team have established a multidisciplinary clinical and laboratory research program at MCRI. This combination of researchers across multiple disciplines is essential to enable understanding of these conditions and translate the results back to patients and families.
Honorary Fellow, The Department of Paediatrics, The University of Melbourne, Australia (from 11th February 2016).
Honorary Fellow, Florey Institute of Neuroscience and Mental Health Research, Australia (from 15th March 2016).
Honorary Fellow, Walter & Eliza Hall Institute of Medical Research, Australia (from 15 August 2018)
MCRI 2019 Professional Development Award, Feb 2020
Victorian Government Pride Events and Festivals 2019-20 fund - QueersInScience Midsumma Lecture Series, Jan 2020
Rebecca L Cooper Project Grant - Improving outcomes for patients undergoing surgery to treat drug resistant epilepsy, Dec 2019
NHMRC Ideas grant - Using Single-Cell Omics to Determine Disease Mechanism and Improve Clinical Management of Children with Epilepsy, Dec 2019
MCRI staff award, Discovery Award, undertaking pioneering work on brain malformations and her advocacy with Queers In Science, Dec 2019
MCRI Pilot Project funding – Determining the molecular signatures of dysmorphic neurons that underlie epileptogenesis, Oct 2019
Science and Technology Australia Pride Scholarship to attend Science meets Parliament Nov 2018
Australian Academy of Science Theo Murphy Initiative – Establishing an National LGBTQIA+ STEMM Network, May 2019
Epilepsy is a disorder of the brain that affects over 20 million children worldwide. Children with epilepsy have recurrent seizures which are can take many forms including staring spells, muscle jerking, loss of consciousness or unusual feelings. Fear, misunderstanding, discrimination and social stigma have surrounded epilepsy for centuries. Early intervention is essential to reduce seizure burden and prevent adverse developmental consequences. Medications are tried first, however in up to one third of children medications fail control their epilepsy, and are often associated with side effects.
One of the most common causes of drug resistant epilepsy in children is a lesion on the brain that is the result of abnormal development during the pregnancy. In such children, surgery to remove the lesion may be curative. Yet, only 16% of countries in the world have epilepsy surgery units (WHO Neurology Atlas, 2017). There is a clear need for new treatment strategies.
It appears that in these lesions that are removed during epilepsy surgery it is a few bad neurons that spoil the electrical pattern of the brain and cause seizures. Traditionally, it has been challenging to distinguish the few bad neurons from the good neurons and this has hampered efforts to understand the cause of the disease and develop treatments to turn off the bad neurons whilst leaving the normal neurons unaffected.
Many of these lesions have histopathological features strikingly similar including highly localized dysplastic cortical tissue that is distinguished by neuronal dyslamination, dysmorphology and immaturity which suggests these clinically distinguished conditions have a shared origin and underlying dysfunction.
One key area of focus is to study the dysplastic brain lesions that are removed by Neurosurgeons at the Epilepsy Surgery unit at the Royal Children's Hospital. We are applying new molecular technologies such as deep genomic sequencing, single cell omics and 3D fluorescent imaging to these lesions to understand the underlying mechanisms of seizure generation and to improve surgical and clinical management.
Yujing Gao, Gabrielle R Wilson, Nicholas Salce, Alexandra Romano, George Damion Mellick, Sarah M Stephenson, Paul Lockhart. Genetic analysis of RAB39B in an early-onset Parkinson's disease cohort. Frontiers in Neurology (Accepted 13/5/2020).
Yujing Gao; Gabrielle R. Wilson; Sarah E.M. Stephenson; Mustapha Oulad-Abdelghani; Nicolas Charlet-Berguerand; Kiymet Bozaoglu; Catriona A. McLean; Paul Q. Thomas; David I. Finkelstein; Paul Lockhart. Distribution of Parkinson’s disease associated RAB39B in mouse brain tissue. Molecular Brain Accepted 10-3-2020.
Megan Spencer-Smith, Jacquelyn L Knight, Emmanuelle Lacaze, Amelia Ceslis, Emily Gibson, Kim Giraudat, Alissandra McIlroy, Lynn K. Paul, Vanessa Siffredi, Melanie Bahlo, Megan Barker, Eleonore Blondiaux, Timothy J Edwards, Catherine Garel, Solveig Heide, Boris Keren, Simone A Mandelstam, Ashley P L Marsh, George McGillivray, Cyril Mignot, Marie-Laure Moutard, Caroline Nava, Kate Pope, Agnès Rastetter, Stéphanie Valence, Sarah E M Stephenson, Thierry Billette de Villemeur, Amanda Wood, IRC5 Consortium, Vicki Anderson, Christel Depienne, Delphine Heron, Paul J Lockhart, Linda J Richards, Elliott H Sherr, Richard J Leventer and Gail A Robinson. Callosal agenesis and congenital mirror movements: clinical, imaging and neuropsychological outcomes associated with DCC mutations, (Accepted 24 Dec 2019, Developmental Medicine & Child Neurology)
Lee WS, Stephenson SEM, Howell KB, Pope K, Gillies G, Wray A, Maixner W, Mandelstam SA, Berkovic SF, Scheffer IE, MacGregor D, Harvey AS, Lockhart PJ, and Leventer RJ. A somatic second hit mutation in DEPDC5 is limited to dysmorphic neurons with maximal mutation load in the seizure onset zone of focal cortical dysplasia (Accepted 22 May 2019, Ann Clin Transl Neur) 2019;6(7):1338-1344.
Stephenson SEM, Owens HG, Richards KL, Lee WS, DArcy C, Barton S, Mandelstam SA, Maixner WJ, MacGregor D, Petrou S, Lockhart PJ, Harvey AS, Leventer RJ. Dysmorphic neuron density is highest in the centre of epileptogenic cortical tubers. bioRxiv. 2019:621607.
Stephenson SEM, Djaldetti R, Rafehi H, Wilson GR, Gillies G, Bahlo M, Lockhart PJ. Familial Early Onset Parkinson's Disease caused by a homozygous frameshift variant in PARK7: clinical features and literature update. Parkinsonism & Related Disorders, 104(5):914-924.
Amor DJ, Stephenson SEM, Mustapha M, Mensah MA, Ockeloen CW, Tankard RM, Phelan D, Marwan Shinawi, de Brouwer APM, Dowling C, Toler T, Sutton VR, Dumić M, Reardon W, Shaw-Smith C, Leventer RJ, Delatycki MB, Kleefstra T, Mundlos S, Mortier G, Bahlo M, Allen NJ and Lockhart PJ. Pathogenic variants in GPC4 cause Keipert syndrome (nasodigitoacoustic syndrome), Am J Hum Genet, 104(5):914-924
Stephenson SEM, Aumann TD, Taylor JM, Riseley JR, Li R, Mann JR, Tomas D, Lockhart PJ. 2018. Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line. Sci Rep. 8, 7528.
Gao Y, Wilson GR, Stephenson SEM, Bozaoglu K, Farrer MJ, Lockhart PJ. 2018. The emerging role of Rab GTPases in the pathogenesis of Parkinson's disease. Mov Disord. 33(2):196-207.
Knight KW, Stephenson SEM, West S, Delatycki MB, Jones CA, Little MH, Patton GC, Sawyer SM, Skinner SR, Telfer MM, Wake M, North KN, Oberklaid F. 2017. The kids are OK: it is discrimination not same-sex parents that harms children. Med J Aust, 207, 374-375.
Stutterd C, Diakumis P, Bahlo M, Fanjul Fernandez M, Leventer RJ, Delatycki M, Amor DJ, Chow CW, Stephenson SEM, Meisler MH, Mclean C, Lockhart PJ. Neuropathology of childhood-onset basal ganglia degeneration caused by mutation of VAC14. Ann Clin Transl Neurol. 4(12), 859-864
Marsh AP, Heron D, Edwards TJ, Quartier A, Galea C, Nava C, Rastetter A, Moutard ML, Anderson V, Bitoun P, Bunt J, Faudet A, Garel C, Gillies G, Gobius I, Guegan J, Heide S, Keren B, Lesne F, Lukic V, Mandelstam SA, McGillivray G, McIlroy A, Méneret A, Mignot C, Morcom LR, Odent S, Paolino A, Pope K, Riant F, Robinson GA, Spencer-Smith M, Srour M, Stephenson SEM, Tankard R, Trouillard O, Welniarz Q, Wood A, Brice A, Rouleau G, Attié-Bitach T, Delatycki MB, Mandel JL, Amor DJ, Roze E, Piton A, Bahlo M, Billette de Villemeur T, Sherr EH, Leventer RJ, Richards LJ, Lockhart PJ, Depienne C. 2017. Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance. Nat Genet, 49, 511-514.
Wilson GR , Sim JC , Mclean C, Giannandrea M , Galea CA , Riseley JR, Stephenson SEM, 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. 2014. Mutations In RAB39B Cause X-Linked Intellectual Disability And Early-Onset Parkinson Disease With Alpha-Synuclein Pathology. Am J Hum Genet, 95, 729-35.
Yiu EM, Tai G, Peverill RE, Lee KJ, Croft KD, Mori TA, Scheiber-Mojdehkar B, Sturm B, Praschberger M, Vogel AP, Rance G, Stephenson SEM, Sarsero JP, Stockley C, Lee CY, Churchyard A, Evans-Galea MV, Ryan MM, Lockhart PJ, Corben LA. & Delatycki, MB. 2015. An Open-Label Trial In Friedreich Ataxia Suggests Clinical Benefit With High-Dose Resveratrol, Without Effect On Frataxin Levels. J Neurol, 262, 1344-53.
Delatycki MB, Tai G, Corben L, Yiu EM, Evans-Galea MV, Stephenson SEM, Gurrin L, Allen KJ, Lynch D & Lockhart PJ. 2014. HFE p.C282Y Heterozygosity Is Associated With Earlier Disease Onset In Friedreich Ataxia. Mov Disord, 29, 940-3.
Stephenson SEM, Taylor JM & Lockhart PJ. 2012. Parkinson's Disease And Parkin: Insights From Park2 Knockout Mice, InTech, 251-276.
Delatycki MB, Wolthuizen M, Collins V, Varley E, Craven J, Allen K J, Gurrin LC, Aitken M, Trembath MK, Bond L, Wilson GR, Stephenson SEM, Macciocca I, Hickerton C, Lockhart PJ & Metcalfe SA. 2012. IronXS: High-School Screening For Hereditary Haemochromatosis Is Acceptable And Feasible. Eur J Hum Genet, 20, 505-9.
O'Sullivan, LA, Liongue, C, Lewis, RS, Stephenson, SEM & Ward, AC, 2007. Cytokine Receptor Signaling Through The Jak-Stat-Socs Pathway In Disease. Mol Immunol, 44, 2497-506.