b'AWARD9 2021 Milton B. Wallack Trainee Award RecipientDea Gorka, BSUCONNSilencing of Paternal UBE3A by UBE3A-ATS Occursthrough Transcriptional InterferenceThis talk focuses on gaining a better understanding of how the interaction between UBE3A-ATS and UBE3A leads to imprinting of UBE3A on the paternal allele in chromosome 15q11-13 in order to learn more about Angelman syndrome (AS) and discover novel therapeutic options for these patients. AS is a neurodevelopmental disorder characterized by motor dysfunction, intellectual disability, severe seizures, absent speech, and a happy demeanor. AS is caused by loss of function from the maternally inherited allele of UBE3A. In most cell types, UBE3A is expressed from both the maternal and paternal alleles. In mature neurons, UBE3A is only expressed from the maternally-inherited allele. Thus, loss of function from the maternal allele leads to nearly complete loss of UBE3A RNA and protein. Imprinted (maternal-only) expression of UBE3A occurs because the paternal allele of UBE3A is silenced by a long non-coding antisense RNA, termed UBE3A-ATS. Activation of paternal UBE3A through the suppression ofUBE3A-ATStranscriptionisapromisingtherapeuticstrategyfor AS,howevertheexactmechanismunderlyingUBE3AimprintingbyUBE3A-ATS is not fully understood. This research uses patient-derived humaniPSCsandtheirneuralderivativestocarefullydissectthe mechanismsbywhichUBE3A-ATSsilencespaternalUBE3Aandhow antisense oligonucleotides (ASOs) unsilence paternal UBE3A.Dea Gorka is currently a 4th year Ph.D. student in the Genetics and Developmental Biology (GDB) area of concentration within the Biomedical Sciences Ph.D. program at the University of Connecticut School of Medicine. Her research focuses on using patient-specific induced pluripotent stem cells (iPSCs) to better understand genetic and cellular deficits underlying two 15q imprinting disorders: Angelman syndrome (AS)and Prader-Willi syndrome (PWS).'