The Intellectual and Developmental Disabilities Research Center (IDDRC) at CHOP/Penn

CHOP/宾夕法尼亚大学智力与发育障碍研究中心 (IDDRC)

• 批准号: 10678888
• 负责人: ERIC D MARSH
• 金额: $ 138.1万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10678888
• 关键词: 22q11; Adult; Advocacy; Advocate; Affective; Award; Behavior; Behavioral; Biological Markers; Biometry; Brain; Cardiology; Caring; Chalk; Child; Child Care; Clinical; Clinical Research; Cognitive; Collaborations; Communities; Complement; Cultural Diversity; Data Analytics; Data Science; Development; Developmental Disabilities; Discipline; Disease; Doctor of Philosophy; Down Syndrome; Early identification; Education; Emotional; Ensure; Experimental Designs; Faculty; Family; Fostering; Foundations; Funding; Future; Future Generations; Genes; Genetic; Genetic Determinism; Genetic Risk; Genomics; Goals; Government Officials; Grant; Human; Individual; Infant; Institution; Intellectual and Developmental Disabilities Research Centers; Intellectual functioning disability; Interdisciplinary Study; Intervention; Lead; Leadership; Magnetoencephalography; Measures; Medical; Medical Research; Mission; Motor; Mus; National Institute of Neurological Disorders and Stroke; Nervous System; Neurobiology; Neurodevelopmental Disability; Neuronal Differentiation; Neurosciences; Output; Pathogenesis; Patients; Pediatric Hospitals; Pennsylvania; Perinatology; Philadelphia; Policy Maker; Population; Positioning Attribute; Prader-Willi Syndrome; Pre-Clinical Model; Program Development; Reproducibility; Research; Research Design; Research Institute; Research Personnel; Research Project Grants; Sample Size; Scientist; Sensory; Series; Services; Structure; Techniques; Technology; Testing; Time; Training; Training Programs; Translational Research; Turner' s Syndrome; Underrepresented Minority; United States; Universities; Vocabulary; Work; auditory processing; behavioral outcome; career; career development; clinical translation; community building; community center; cost effective; data integration; design; disability; effective intervention; genetic variant; improved; induced pluripotent stem cell; innovation; language outcome; member; multidisciplinary; neural circuit; neuroimaging; neuromechanism; new technology; novel; novel marker; patient oriented; pharmacologic; post-doctoral training; professor; programs; recruit; social; sound; support network; therapy development; translational impact

(RESEARCH PLAN- OVERALL) PROJECT SUMMARY With this application, we seek funding for the Intellectual and Developmental Disabilities Research Center (IDDRC) at the Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania (Penn), which has been continuously funded for the past 30 years. Our IDDRC supports an interdisciplinary program and is the chief agency at CHOP/Penn for the promulgation of research into the Intellectual and Developmental Disabilities (IDDs). Our mission, to identify the pathogenesis of and develop therapies for individuals with IDDs, is pursued through three aims. (Aim 1) Lead a cutting-edge IDD research agenda. We will support five research cores that harness innovations in genetics and neuroscience to identify the causes of IDDs, to determine how gene variants alter brain structure, circuitry, and behavioral outputs (cognitive, motor, sensory, social, affective), and to utilize this information to develop biomarkers and new treatments for IDDs. Our cores deploy complementary state-of- the-art technologies, focusing on studies performed in two species (mouse & human), making it easier for center members to perform more impactful research. Cores emphasize research along the developmental spectrum. These strategies ensure that the advances will have a translational impact. The cores provide cost-effective support for 61 world-class center members, who are funded by 78 grants totaling $29.1 million annually to study the pathogenesis of IDDs, to identify new biomarkers of IDDs, and to develop novel interventions (pharmacologic and genetic). In addition, we will support an innovative research project that uses center cores to determine if magnetoencephalography (MEG) measures of auditory processing in infants at genetic risk for IDD can be used to predict cognitive and language outcome. Our cores focus on rigorous and reproducible research practices, including sound experimental design for hypothesis testing, well-justified sample sizes, and robust data analytics. (Aim 2) Lead a multi-disciplinary career development program to support trainees and early-stage faculty. Our trainees are diverse and have PhDs, MDs, and MD/PhDs with backgrounds in genetics, neuroscience, and related disciplines. They receive support from IDDRC-administered programs: a NINDS-funded T32 Training Grant in Neurodevelopmental Disabilities, a CHOP Research institute-funded supplement program for clinical research fellows, and a CHOP-institute funded New Program Development award for Assistant Professors. They obtain multidisciplinary training that helps them become future leaders in IDD research. (Aim 3) Support Networking/Collaboration, Advocacy, and the Dissemination of IDD Research findings. The Center leadership will enable networking to support collaborative initiatives, both within the CHOP/Penn IDDRC community and between IDDRCs. Center leadership will advocate both internally and externally to advance an IDD research agenda. Finally, the Center will lead an effort to disseminate research advances to patients, their families, to government officials, and to other scientists. With this comprehensive approach, the IDDRC at CHOP and Penn will achieve our goal of advancing patient-centered innovative treatments for individuals with IDDs.

（总体研究计划）

项目成果

Dichloroacetate and thiamine improve survival and mitochondrial stress in a C. elegans model of dihydrolipoamide dehydrogenase deficiency.

• DOI: 10.1172/jci.insight.156222
• 发表时间: 2022-10-24
• 期刊: JCI INSIGHT
• 影响因子: 8
• 作者: Broxton, Chynna N.;Kaur, Prabhjot;Lavorato, Manuela;Ganesh, Smruthi;Xiao, Rui;Mathew, Neal D.;Nakamaru-Ogiso, Eiko;Anderson, Vernon E.;Falk, Marni J.
• 通讯作者: Falk, Marni J.

Pathogenic mtDNA variants, in particular single large-scale mtDNA deletions, are strongly associated with post-lingual onset sensorineural hearing loss in primary mitochondrial disease.

• DOI: 10.1016/j.ymgme.2022.09.002
• 发表时间: 2022-11
• 期刊: MOLECULAR GENETICS AND METABOLISM
• 影响因子: 3.8
• 作者: Elander, Johanna;McCormick, Elizabeth M.;Varendh, Maria;Stenfeldt, Karin;Ganetzky, Rebecca D.;Goldstein, Amy;Zolkipli-Cunningham, Zarazuela;MacMullen, Laura E.;Xiao, Rui;Falk, Marni J.;Ehinger, Johannes K.
• 通讯作者: Ehinger, Johannes K.

Identifying electrophysiological markers of autism spectrum disorder and schizophrenia against a backdrop of normal brain development.

• DOI: 10.1111/pcn.12927
• 发表时间: 2020-01
• 期刊: PSYCHIATRY AND CLINICAL NEUROSCIENCES
• 影响因子: 11.9
• 作者: Edgar, J. Christopher

DELongSeq for efficient detection of differential isoform expression from long-read RNA-seq data.

• DOI: 10.1093/nargab/lqad019
• 发表时间: 2023-03
• 期刊: NAR genomics and bioinformatics
• 影响因子: 4.6

Impaired Maternal-Fetal Environment and Risk for Preoperative Focal White Matter Injury in Neonates With Complex Congenital Heart Disease.

• DOI: 10.1161/jaha.122.025516
• 发表时间: 2023-04-04
• 期刊: JOURNAL OF THE AMERICAN HEART ASSOCIATION
• 影响因子: 5.4
• 作者: Licht, Daniel J.;Jacobwitz, Marin;Lynch, Jennifer M.;Ko, Tiffany;Boorady, Timothy;Devarajan, Mahima;Heye, Kristina N.;Mensah-Brown, Kobina;Newland, John J.;Schmidt, Alexander;Schwab, Peter;Winters, Madeline;Nicolson, Susan C.;Montenegro, Lisa M.;Fuller, Stephanie;Mascio, Christopher;Gaynor, J. William;Yodh, Arjun G.;Gebb, Juliana;Vossough, Arastoo;Choi, Grace H.;Putt, Mary E.
• 通讯作者: Putt, Mary E.