I am a geneticist and researcher with board certifications in pediatrics, medical genetics, and molecular genetics. The broad goal of my research is to understand the causes, mechanisms and outcomes of human developmental brain disorders, including brain growth abnormalities (megalencephaly, microcephaly),  malformations of cortical development and associated co-morbidities including autism, epilepsy and intellectual disability. My work has led to gene discovery for several disorders associated with brain growth dysregulation including megalencephaly (e.g. PIK3CA, PIK3R2, AKT3, MTOR, CCND2) and microcephaly (e.g. STAMBP, CENPE, KIF11, CDC42), among several others (Mirzaa et al., Neuropediatrics 2004; Mirzaa et al., AJMG 2012; McDonnell et al., Nature Genetics 2013; Mirzaa et al., Pediatric Neurology 2013; Mirzaa et al., Human Genetics 2014; Martinelli et al., American Journal of Human Genetics 2018). My work on the PI3K-AKT-MTOR related brain overgrowth disorders has led to the identification of several genes within this pathway that cause brain growth dysregulation and focal cortical dysplasia, with important therapeutic implications using PI3K-AKT-MTOR pathway inhibitors (Rivière et al., Nature Genetics 2012; Mirzaa et al., Nature Genetics 2014; Jansen et al., Brain 2015; Mirzaa et al., Lancet Neurology, 2015; Mirzaa et al., JAMA Neurology, 2016).

My lab is focused on identifying the molecular and cellular mechanisms of developmental brain disorders and translating these genomic discoveries to molecularly-guided therapies using high throughput genomic, transcriptomic, and proteomic methods in relevant human tissues, combined with functional validation of genetic variants using human reprogramming and genome editing via CRISPR-Cas9 methods. My lab houses the first human stem cell tissue culture facility at the Seattle Children’s Research Institute (SCRI) solely dedicated to generating human induced Pluripotent Stem Cells (iPSCs), Neural Progenitor cells (NPCs), cortical neurons and cerebral organoids to model genetic variants that are of high relevance to neurodevelopmental disorders, and to be used as a platform for future pre-clinical high throughput drug screening. My lab has the necessary resources, expertise and equipment to execute the proposed experiments. Extensive collaborations with experts in these methods, combined with excellent infrastructural resources at SCRI and the University of Washington (UW), further ensure successful completion of this project.