Epilepsy Functional Genomics Group

The most severe childhood epilepsies are caused by genetic variants in ion channels and synaptic proteins. Their severity is determined by the occurrence of seizures that are resistant to treatment by anti-seizure medications and are accompanied by neurodevelopmental delay, psychiatric manifestations, movement disorders and autism. Our group specialises in modelling these epilepsy forms (also known as developmental and epileptic encephalopathies) using a variety of biological systems to investigate the disease mechanisms and test innovative therapies using state-of-the-art functional and genomic approaches.

Our group works with the Ion Channels and Human Diseases Group on several major projects including the development of induced pluripotent stem cell models and antisense therapies for neurogenetic disorders. Our projects are highly translational as we work closely with clinical teams and industrial partners. Our group is home to researchers with expertise in various areas such as molecular biology, bioinformatics, stem cell biology, electrophysiology, and functional imaging.

Research interests

  • Genetic epilepsy
  • Early childhood genetic epilepsy syndrome
  • Induced pluripotent stem cell-derived neuronal models
  • Functional analyses of cellular activity in a range of
    biological systems
  • RNA-targeted therapeutics

  • Generating iPSC-derived neuronal models (monolayer cultures and brain organoids)
  • 2-photon calcium imaging
  • High throughput in vitro cell screening
  • QPCR, digital PCR
  • RNA sequencing
  • Bioinformatic gene expression analysis

About our research

We aim to model genetic epilepsies and develop novel therapies.

Our model systems include mammalian cell lines, genetic mouse models and human stem cell-derived neuronal models (2D and 3D). Molecular techniques are used to validate the specific models established while functional assays and genomic profiling can reveal the disease mechanism and test the efficacy of novel treatments.

Antisense oligonucleotides are designed in the lab based on the gene expression requirements for the gene of interest. Bioinformatics workflows are incorporated to filter the ASOs for toxicity/non-specific targets. The ASOs are then screened in in vitro cell-based assays that are suitable for high-sensitivity read-outs. The regulation of the transcript expression is confirmed at the protein level by western blotting/mass spectrometry. The main methods adopted include high-throughput gene expression analysis in various immortalised cell lines and in iPSC-derived neurons using qPCR and digital PCR. RNA sequencing (short and long read sequencing) is also adopted to understand transcriptome-wide gene expression changes.



‘Research is more than an academic pursuit; it’s about helping people and giving hope.’

Research team

Research team head

Team members

Research fellows

  • Dr Sannu Thomas
  • Dr Cristiana Mattei
  • Dr Miaomiao (Cherry) Mao
  • Dr Selvam Paramasivan
  • Dr Jana Janaththani
  • Dr Julia Loseff-Silver

Research and technical staff

  • Alicia Sedo
  • Helen Kopsidas
  • Erlina Syazwan

Phd students

  • Montanna Waters
  • Lucas Teasdale
  • Danielle Apted

Honours students

  • Sarah Handcock

Selected publications

  • Mao M, Mattei C, Rollo B, Byars SG, Cuddy C, Berecki G, Heighway J, Pachernegg S, Menheniott T, Apted D, Jia L, Dalby K, Nemiroff A, Mullen S, Reid C, Maljevic S and Petrou S (2023), ‘Distinctive in vitro phenotypes in iPSC-derived neurons from patients with gain- and loss-of-functionSCN2Adevelopmental and epileptic encephalopathy’, bioRxiv (Cold Spring Harbor Laboratory), doi:10.1101/2023.02.14.528217
  • Heighway J, Sedo A, Garg A, Eldershaw L, Perreau V, Berecki G, Reid C, Petrou S and Maljevic S (2022), ‘Sodium channel expression and transcript variation in the developing brain of human, Rhesus monkey, and mouse’, Neurobiology of Disease, 164:105622. doi:10.1016/j.nbd.2022.105622
  • Burbano L, Li M, Jancovski N, Jafar-Nejad P, Richards K, Sedo A, Soriano A, Rollo B, Jia L, Gazina EV, Piltz S, Adikusuma F, Thomas PG, Kopsidas H, Rigo F, Reid CA, Maljevic S and Petrou S (2022), ‘Antisense oligonucleotide therapy for KCNT1 encephalopathy’, JCI insight, 7(23), doi:10.1172/jci.insight.146090
  • Rosa F, Dhingra A, Uysal B, Mendis C, Loeffler H, Elsen GE, Mueller SG, Schwarz N, Castillo-Lizardo M, Cuddy CE, Becker F, Heutink P, Reid CA, Petrou S., Lerche H and Maljevic S (2020), ‘In vitro differentiated human stem cell-derived neurons reproduce synaptic synchronicity arising during neurodevelopment’, Stem cell reports, 15(1):22–37, doi:10.1016/j.stemcr.2020.05.015

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