Stormy J. Chamberlain, Ph.D.
Assistant Professor of Molecular Genetics
Department of Genetics and Genome Sciences
My lab uses human induced pluripotent stem cells (iPSCs) to model and study genomic imprinting disorders caused by copy number variation at chromosome 15q11-q13. Three such disorders arise from the deletion or duplication of this genetic region: Prader-Willi syndrome (PWS), Angelman syndrome (AS), and Dup15q syndrome (Dup15q). PWS is caused by deletions of the pateral allele of 15q11-q13, while AS and Dup15q are caused by deletions and duplications of the same region, respectively. My lab focuses on the latter two disorders. Individuals with AS are non-verbal, have intellectual disability, suffer from difficult to treat seizures, and walk with an unsteady gait. These delightful kids also have a characteristic happy demeanor. Individuals with Dup15q syndrome are developmentally delayed, have intellectual disability, have speech and language disorder, and difficult to treat seizures. Individuals with Dup15q often meet criteria for autism, and duplications of 15q11-q13 are one of the most common genetic aberrations associated with autism.
AS results from the loss of function from maternal copy of the UBE3A gene, which encodes an E3 ubiquitin ligase. UBE3A is expressed only from the maternally-inherited copy of chromosome 15 in neurons. A long, non-coding antisense transcript represses the paternal copy. My lab is trying to determine how and when paternal UBE3A becomes silenced during neural development in humans. We are also trying to reactivate paternal UBE3A in AS iPSC-derived neurons, as a potential therapeutic approach for this disorder. Dup15q results from increased expression from maternal 15q11-q13. Although there are several other genes in the region, UBE3A likely plays a major role in the disorder. We are modulating the expression of the different genes in this region to determine which genes are the most important for the features of Dup15q syndrome. My lab uses genome editing tools (CRISPR), neuronal differentiation strategies, and various genomics technologies to address these questions.