What is the molecular genetic basis of neurodevelopmental disorders?
Welcome to the Girirajan Lab website!
The primary focus of our research is to discover and characterize
genetic changes including genomic deletions and duplications and single
nucleotide mutations contributing to neurodevelopmental disorders such
as autism, intellectual disability, schizophrenia, epilepsy and congenital malformation.
The Girirajan Laboratory is interested in untangling the genetic and phenotypic heterogeneity associated with neurodevelopmental
disorders, including autism spectrum disorders, schizophrenia, epilepsy, and intellectual disability. There is extensive genetic heterogeneity
(i.e. more than one gene or genomic region implicated) for neurodevelopmental disorders, suggesting a larger genetic target. Even among individuals carrying the same genetic variant, significant phenotypic heterogeneity (difference in the clinical presentation) has been documented.
This has posed considerable challenges in understanding the role of discovered genetic variants in terms of disease
causation, diagnosis, and interpretation for management and treatment. The function of these variants in the etiology and pathogenesis of
neurodevelopmental disorders is unknown. Our research incorporates high-throughput genomic techniques including array comparative genomic hybridization,
genome and transcriptome sequencing, computational approaches, and model organisms to understand the genetic basis of human complex disease.
Our ongoing projects and long-term goals are related to the following:
Discovering causative genes and genomic regions as well as modifiers in affected children and families to facilitate improved diagnosis, management, and counseling
Recapitulating neurodevelopmental phenotypes in model organisms by engineering mutations in disease-associated genes
Elucidation of disease-associated functional pathways to identify vulnerable and effective molecular targets for therapy
Our lab combines experimental human genetics, functional genomics in model
organisms, and computational genomics to understand the molecular etiology of
neurodevelopmental disorders. We welcome applications from talented and committed individuals who are interested in studying human disease. Please send
inquiries to sxg47@psu.edu.
Video from PSU Eberly College of Science Instagram
The Girirajan Lab is now recruiting patients and families carrying rare copy-number variants for a study on the clinical variability
associated with these disorders. If you are interested in participating, please find more information and fill out a questionnaire here.
Neurodevelopmental phenotypes are modulated by rare mutations in the genetic background
A project led by graduate student Lucilla Pizzo found that the burden of rare mutations in the genetic background
can explain differences in clinical features of patients with the same disease-associated mutation. This study was recently published in Genetics in Medicine.
Complex genetic interactions within the 16p11.2 CNV contribute to neurodevelopmental defects
A project led by post-doctoral scholars Janani Iyer and Dhruba Singh used Drosophila models to show that multiple genes within the 16p11.2 CNV region interact with each other through conserved cell proliferation pathways, leading to defects in neuronal development. This study was recently published in Nature Communications.
