For 46 years, the Birth Defects Research Laboratory (BDRL) has been the major NIH-funded site for collection and distribution of conceptal tissues. The availability of viable conceptal organs and tissues has made the Laboratory a unique and critical non-profit resource for biomedical research. This application seeks to continue and further develop the core fundamental goal of the laboratory: the systematic collection, staging, identification, and processing of normal specimens and distribution of their tissues to recipients. In this renewal application, we will build upon this central aim to extend the biomedical research resource further by making available samples for DNA/RNA extraction and epigenetic assays. In addition, the investigator will develop the resource by 1) extending the systematic collection, identification, and distribution to abnormal fetuses; 2) correlating prenatal data with the post-termination findings from examination/postmortem; 3) exploiting the virtual histological and phenotyping capabilities of tissue imaging platforms after performing proof-of-principle studies in genitourinary tract and cardiovascular tissues; 4) capitalizing on the expected enrichment of genetic defects underlying fetal congenital anomalies by generating copy number variant data through array-based comparative genomic hybridization studies; 5) systematically making accessible tissues and their data for investigators; and 6) engaging and working with key collaborators to improve services and increase recipient numbers in their respective fields. This application builds upon ARRA support, evaluating the utility of novel tissue imaging systems to enhance BDRL services, and stimulating and supporting research based in part on this resource into the bases of birth defects and normal development. Systematically characterizing abnormal fetuses and distributing tissues from these fetuses will exploit the unique positioning of the BDRL to develop this as a significant research resource and service to researchers who seek to understand the underlying developmental biology of normal and abnormal human development.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Resource-Related Research Projects (R24)
Project #
5R24HD000836-51
Application #
8882485
Study Section
Biobehavioral and Behavioral Sciences Subcommittee (CHHD)
Program Officer
Hewitt, Tyl
Project Start
1979-05-01
Project End
2017-06-30
Budget Start
2015-07-01
Budget End
2017-06-30
Support Year
51
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Washington
Department
Pediatrics
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Menon, Rajasree; Otto, Edgar A; Kokoruda, Austin et al. (2018) Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney. Development 145:
Dame, Michael K; Attili, Durga; McClintock, Shannon D et al. (2018) Identification, isolation and characterization of human LGR5-positive colon adenoma cells. Development 145:
Cox, Liza L; Cox, Timothy C; Moreno Uribe, Lina M et al. (2018) Mutations in the Epithelial Cadherin-p120-Catenin Complex Cause Mendelian Non-Syndromic Cleft Lip with or without Cleft Palate. Am J Hum Genet 102:1143-1157
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An, Joon-Yong; Lin, Kevin; Zhu, Lingxue et al. (2018) Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder. Science 362:
Marcu, Raluca; Choi, Yoon Jung; Xue, Jun et al. (2018) Human Organ-Specific Endothelial Cell Heterogeneity. iScience 4:20-35
Sosa, Enrique; Chen, Di; Rojas, Ernesto J et al. (2018) Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche. Nat Commun 9:5339
Miller, Alyssa J; Hill, David R; Nagy, Melinda S et al. (2018) In Vitro Induction and In Vivo Engraftment of Lung Bud Tip Progenitor Cells Derived from Human Pluripotent Stem Cells. Stem Cell Reports 10:101-119
Andrews, Allison M; Lutton, Evan M; Cannella, Lee A et al. (2018) Characterization of human fetal brain endothelial cells reveals barrier properties suitable for in vitro modeling of the BBB with syngenic co-cultures. J Cereb Blood Flow Metab 38:888-903
Borgmann, Kathleen; Ghorpade, Anuja (2018) Methamphetamine Augments Concurrent Astrocyte Mitochondrial Stress, Oxidative Burden, and Antioxidant Capacity: Tipping the Balance in HIV-Associated Neurodegeneration. Neurotox Res 33:433-447

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