Biology subjects

Jurgens, J. A.

Publications and source records attributed to Jurgens, J. A..

3 recordsLinked to original sources

bioRxiv2026

The Common Fund Data Ecosystem (CFDE)

The NIH Common Fund Data Ecosystem (CFDE) integrates data resources from 18 NIH Common Fund programs for discovery and integrative analysis. These programs generate valuable but heterogeneous datasets that can be difficult to discover, access, and reuse. CFDE aims to provide a collaborative, community-built infrastructure that links and enriches Common Fund programs. We describe the evolution, structure, and core technologies of CFDE, including practical approaches that support submission, integration, visualization, and public release of multimodal data. Training programs and workforce initiatives lower barriers to adoption. CFDE has devised solutions to critical issues facing cross-program initiatives, including data scale and heterogeneity, dataset integration, and long-term sustainability. We demonstrate the utility of linking Common Fund resources through integrative tools and cross-dataset queries to yield insights that would otherwise be infeasible. Collectively, CFDE shows that a standards-driven, federated approach enhances and unifies cross-disciplinary resources, fostering collaboration and data-driven discovery.

scientific communication and education↗

bioRxiv2024

Gene identification for ocular congenital cranial motor neuron disorders using human sequencing, zebrafish screening, and protein binding microarrays

PurposeTo functionally evaluate novel human sequence-derived candidate genes and variants for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs). MethodsThrough exome and genome sequencing of a genetically unsolved human oCCDD cohort, we previously identified variants in 80 strong candidate genes. Here, we further prioritized a subset of these (43 human genes, 57 zebrafish genes) using a G0 CRISPR/Cas9-based knockout assay in zebrafish and generated F2 germline mutants for seventeen. We tested the functionality of variants of uncertain significance in known and novel candidate transcription factor-encoding genes through protein binding microarrays. ResultsWe first demonstrated the feasibility of the G0 screen by targeting known oCCDD genes phox2a and mafba. 70-90% of gene-targeted G0 zebrafish embryos recapitulated germline homozygous null-equivalent phenotypes. Using this approach, we then identified three novel candidate oCCDD genes (SEMA3F, OLIG2, and FRMD4B) with putative contributions to human and zebrafish cranial motor development. In addition, protein binding microarrays demonstrated reduced or abolished DNA binding of human variants of uncertain significance in known and novel sequence-derived transcription factors PHOX2A (p.(Trp137Cys)), MAFB (p.(Glu223Lys)), and OLIG2 (p.(Arg156Leu)). ConclusionsThis study nominates three strong novel candidate oCCDD genes (SEMA3F, OLIG2, and FRMD4B) and supports the functionality and putative pathogenicity of transcription factor candidate variants PHOX2A p.(Trp137Cys), MAFB p.(Glu223Lys), and OLIG2 p.(Arg156Leu). Our findings support that G0 loss-of-function screening in zebrafish can be coupled with human sequence analysis and protein binding microarrays to aid in prioritizing oCCDD candidate genes/variants.

neuroscience↗

bioRxiv2019

Tandem Requirement for Full Renal D1R and D5R Activity

The peripheral dopaminergic system promotes the maintenance of blood pressure homeostasis by engendering natriuresis, mainly through the renal D1R and D5R receptors. This effect is most apparent under conditions of moderate body sodium excess. Human and rodent renal proximal tubules express both receptors, which share common structural features and pharmacological profiles. Genetic ablation of either receptor in the kidney results in hypertension in mice. In this study, we demonstrated that in renal proximal tubules, these two receptors colocalized, co-immunoprecipitated, co-segregated in lipid rafts, and heterodimerized with one another, which was enhanced by treatment with the D1R/D5R agonist fenoldopam (1 M, 30 min). Gene silencing via antisense oligonucleotides in renal proximal tubule cells abrogated cAMP production and sodium transport in response to fenoldopam. Our results highlight the cooperation and co-dependence of these two receptors through heterodimerization in renal proximal tubule cells.

molecular biology↗