Kiara Grasso

I am a provisional PhD candidate studying the genetic and molecular mechanisms underpinning epilepsy, with a particular focus on developmental and epileptic encephalopathies (DEE). I completed my honours thesis on "Epigenome and Transcriptome Biomarker Analysis in Monogenic Epilepsy", and am continuing my study within this field through my PhD. 

Epilepsy is a complex neurodevelopmental disorder characterised by a persistent propensity to recurrent, spontaneous, and unpredictable seizures. Affecting over 70 million individuals worldwide, epilepsy accounts for approximately one percent of the global disease burden. DEEs are severe epilepsies, defined by frequent, commonly medication resistant, seizures and developmental slowing or regression. Variants in PCDH19 cause a DEE known as PCDH19 clustering epilepsy (PCDH19-CE). PCDH19-CE is characterised by clustered, and often fever-induced, seizures that onset in infancy and offset during adolescence. Seizures are commonly accompanied by neuropsychiatric comorbidities such as intellectual disability, autism spectrum disorder, and, in some cases, psychotic disorders. Many patients are refractory to treatment with antiseizure medications; however, neuropsychiatric symptoms frequently persist even when seizure control is achieved.

Under the supervision of Dr. Mark Corbett and Prof. Jozef Gecz, my research aims to investigate the molecular pathogenesis of PCDH19-CE through examination of PCDH19 variants and their associated phenotype, analysis of disrupted signalling and gene regulation pathways, and assessment of how mosaic expression patterns of PCDH19 influence phenotypic severity. This research aims to meaningfully contribute to the understanding of the pathogenesis of PCDH19-CE, and to subsequently advance the identification or development targeted interventions for this complex disorder.