The CHRNA7 gene, which encodes the alpha7 nicotinic acetylcholine receptor, plays a prominent role in the etiology of neuropsychiatric disease (intellectual disability, epilepsy, autism, bipolar disorder, and others). We have collected a large cohort of families with CHRNA7 mutations (deletions, duplications, triplications, point mutations), and are studying their clinical, behavioral, and electrophysiological phenotypes.
In the laboratory, we study the genetics of CHRNA7 and its chimeric fusion gene, CHRFAM7A, which is a human-specific paralog that has arisen by segmental duplication during human evolution. Using molecular, biochemical, mouse genetic, and behavioral analyses, as well as induced pluripotent stem cell technology, we investigate the role of CHRFAM7A and its physical and functional interaction with CHRNA7.
MAGEL2 is a maternally imprinted, paternally expressed gene on chromosome 15q11 in the region critical for Prader-Willi syndrome. The protein encoded by MAGEL2 facilitates ubiquitination of the WASH complex, and endosomal protein recycling. Our team has identified that individuals with truncating mutations in MAGEL2 manifest a condition that has significant overlap with Prader-Willi syndrome, yet is distinct due to the presence of joint contractures and a higher prevalence of autism spectrum disorder (Schaaf-Yang syndrome, OMIM #615547).
In the laboratory, we investigate the unique therapeutic potential of MAGEL2 in the context of Prader-Willi syndrome and Schaaf-Yang syndrome, aiming to identify molecules that unsilenced its “dormant” maternal allele. In addition, we explore MAGE-L2 and its key protein interactors in the context of endosomal protein recycling, a molecular pathway poised to play an important role in intellectual disability, autism, and associated disorders.
Mutations in NR2F1 are the cause of Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (OMIM #615722), a neurodevelopmental disorder characterized by optic nerve atrophy with vision loss, intellectual disability, hypotonia, and other neurological and behavioral features. The protein encoded by NR2F1, an orphan nuclear receptor and transcription factor, plays a critical role in the establishment of fiber tracts and projections in the developing brain.
Our lab investigates the critical molecular pathways involved, and we use translational approaches to better understand the role of this gene in neurodevelopment.