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WASHINGTON UNIVERSITY INTELLECTUAL AND DEVELOPMENTAL DISABILITIES RESEARCH CENTER

华盛顿大学智力与发育障碍研究中心

基本信息

批准号：
9750055
负责人：
JOHN N. CONSTANTINO
金额：
$ 128.6万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-18 至 2020-07-27
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9750055
关键词：
Affect Animal Model Behavior Behavioral Biological Markers Biological Models Brain Caliber Cell model Cells Child Clinical Clinical and Translational Science Awards Clinical assessments Collection Core Facility Data Derivation procedure Development Developmental Disabilities Early Intervention Environment Epigenetic Process Etiology Family Female Fostering Generations Genetic Genetic Predisposition to Disease Genomic approach Genomics Goals Human Image Individual Inherited Intellectual functioning disability Interruption Intervention Knowledge Mental Retardation and Developmental Disabilities Research Centers Molecular Nature Neurodevelopmental Disability Neurology Newborn Infant Pathogenesis Pathogenicity Patients Phenotype Population Population Attributable Risks Predisposition Prevention Preventive Intervention Process Psychiatry Research Research Personnel Research Project Grants Resources Risk Science Scientific Advances and Accomplishments Structure Synapses Syndrome Translating Translational Research Translations Universities Variant Washington autism spectrum disorder autistic brain behavior cognitive neuroscience design developmental disease effective intervention frontier functional genomics human subject indexing innovation medical schools neuroimaging next generation novel premature prenatal preservation prevent programs public health relevance relating to nervous system resilience sex treatment response white matter injury

项目摘要

DESCRIPTION (provided by applicant): The last decade of research in intellectual and developmental disabilities (IDD) has been notably characterized by rapid advances in understanding the nature and complexity of inherited susceptibilities to IDD, but genetic discovery has not yet fulfilled the promise of more effective intervention, even for monogenic IDD syndromes. It is the immediate priority of a next generation of research to capitalize upon knowledge about causation in IDD (both genetic and environmental) and translate it into higher-impact intervention for as many individuals and families affected as possible. In the second cycle of the IDDRC at Washington University in St. Louis (IDDRC@WUSTL), our strategy for contributing to this effort preserves our Center's original focus on characterization of white matter injury to the newborn brain, but extends the scope of Core activity to facilitate a comprehensive approach to understanding and preventing developmental disorders of neural connectivity at the respective levels of cell, synapse, circuit, and behavior, and brings on line major strengths of WUSTL in genomics, behavioral/cognitive neuroscience, and clinical-translational science. The overarching goals of our Center are as follows: (1) To facilitate high-caliber, translational research on the pathogenesis and treatment of IDDs by sustaining an innovative Core structure that attracts and supports qualified, collaborative investigators, and interacts synergistically with complementary Core facilities of other U.S. IDDRCs. We propose to support an Administrative Core, a Developmental Neuroimaging Core, a Model Systems Core (encompassing capacity and expertise for both animal and cellular models of IDD), and a Clinical Translational Core. (2) To cultivate nodes of interdisciplinary scientific activity in frotiers of IDD research which are critical for the derivation of higher-impact treatment and preventive intervention, across 4 major themes: (i) The prevention of prematurity and its neurodevelopmental consequences; (ii) The elucidation of robust intermediate DD phenotypes (as markers of pathogenic processes, targets of early intervention, and indices of response to treatment); (iii) In-depth characterization of the developing human brain, and (iv) Functional genomic approaches to elucidating convergent mechanisms of IDD pathogenesis. (3) To conduct a signature research project that represents a bold, critical step toward higher-impact intervention for IDD, capitalizes upon both the Core structure of our IDDRC and institutional strengths at WUSTL, and epitomizes the manner in which our IDDRC facilitates trans-disciplinary research. Our project is designed to elucidate mechanisms of sex-specific modulation-of-expression of inherited risk for autism spectrum disorders, at the respective levels of cell, brain, and behavior. A goal is to identify compensatory mechanisms underlying resilience among females in ASD-affected families, for the purpose of recapitulating those mechanisms in novel interventions which would be of major relevance to a large proportion of the population of individuals at risk or affected by familial autistic syndromes.