PROJECT SUMMARY/ABSTRACT The Birth Defects Research Laboratory (BDRL) is the only NIH-funded fetal tissue repository available to scientific recipients in the US. HFT is irreplaceable for biomedical research because animal and cellular models of human development and disease do not fully match or recapitulate human development and disease. Also, differences in brain and other organs in development have been identified between humans and animal models. Animal and cellular models may not contain the full mixture of cell types or fully mimic tissue/organ structure. Engineered mutations in developmental genes maybe embryonically lethal in model organisms rendering such genes intractable to study by this approach. Creation of humanized mice to model human infectious, immunological and neoplastic diseases requires xenografting of HFT. Comparison between model systems and native human tissue including HFT is required to ensure that conclusions based on model systems are applicable to human biology and medicine. Further, human-specific genes cannot be studied in model organisms and adult-stem cells cannot be used to study all disorders, especially those that have a base in prenatal development. The BDRL is therefore a crucial scientific resource to retain for facilitating biomedical research progress, especially since alternative commercial laboratories maybe embroiled in controversy related to accusations of trade in HFT. The near 60-year track record and success of the BDRL has been proven many times over from consistent provision of recipient-related scientific services with HFT, fully compliant with strict ethical and research guidelines, without transgression. Spectacular technological advances in biology, notably -omics have greatly expanded research opportunities for utilizing HFT to facilitate novel insights. These advances confirm the rationale for the laboratory to continue to innovate and undertake collaborations to evaluate and synergistically demonstrate novel experimental approaches to maximize the scientific utility of HFT. This application seeks to develop the resource beyond the core fundamental goal of the systematic collection and processing of fetal specimens for distribution of HFT and biologics to recipients. We propose to further develop the research resource by continuing to engage with collaborators to synergistically develop their research and develop our expertise and services. Concurrently, this serves to promote awareness of the laboratory to increase recipient recruitment, as well as enhance research progress into the bases of human development and disease.