4e-2 Preclinical Models of Genetic Neurodevelopmental Disorders: Advancing Therapeutics
Project Description:
Preclinical Models of Genetic Neurodevelopmental Disorders
Dr. Silverman studies rare genetic disorders characterized by intellectual disabilities and pediatric epilepsies. Her laboratory has a large sub-focus on genetic disorders of the chromosomal region 15q11.2-q13, a maternally derived duplication of the 15q11.2-q13 region. It is the second most common genetic variation associated with ASD and a common cause of ID (~1:250-500 of ASD cases; ~1:584 cases of ID). She is leading a project focused on identifying the phenotypes associated with isoform specific Ube3a overexpression in neurons. This is the only NIH-funded work focused on splice variants of the Ube3a gene in vivo. She works in collaboration with multiple parent groups and disability organizations to develop genetic models that will translate into clinical practice more rapidly. In fact, this year, her lab received a UC Davis SOM Cultivating Team Science Award 05/01/2022-04/30/2024. Dr. Silverman has continued this research focus testing antisense oligonucleotides for two disorders of the Dup15q region, both with an industry partner. Over the past several years, the Silverman laboratory's group at the MIND Institute extended the Overarching Project entitled Preclinical Models of Genetic Neurodevelopmental Disorders by implementing a research operation that uses multi-faceted approaches in order to: 1) define clinically relevant outcome-measures and identify biological markers (biomarkers) using genetic and environmental exposure models of intellectual disability (ID), and pediatric epilepsy, examples include gait and sleep signatures; 2) develop rigorous methods for phenotypic detection in mouse and rat models of neurodevelopmental disorders; and 3) utilize innovative, non-behaviorally based phenotypes, in rodent models, such as ex and in vivo neuroimaging, and in vivo neurophysiology while awake and in the home cage and behaving in cognitive tests including EEG, sleep/circadian analysis and sleep spindle modulation, which are translationally relevant biomarkers for multiple brain disorders
Core Function(s):
Performing Research or Evaluation
Area of Emphasis
Health-Related Activities, Quality of Life, Other - Leadership
Target Audience:
Students/Trainees (long or intermediate trainees), Community Trainees / Short term trainees, Professionals and Para-Professionals, Family Members/Caregivers, Adults with Disabilities, Children/Adolescents with Disabilities/SHCN, Legislators/Policy Makers, General Public
Unserved or Under-served Populations:
Other
Primary Target Audience Geographic Descriptor:
State, National, International
COVID-19 Related Data:
N/A
