Biomedical subjects

Paul A Trainor

Publications and source records attributed to Paul A Trainor.

3 recordsLinked to original sources

PubMed2026

Manipulation of protein translation and stem cell self-renewal by CRISPR activation of rRNA transcription.

Ribosomal RNA (rRNA) transcription rates vary during development, and their dysregulation is linked to diseases such as cancer and ribosomopathies. Owing to their high abundance and genomic redundancy, the functional significance of rRNA levels remains unclear. We developed TAPIR (Targeted Activation of Protein Translation), a CRISPR-based approach to elevate rRNA levels by inducing 47S ribosomal DNA transcription. TAPIR increased nucleolar size and enhanced protein synthesis, even in rapidly proliferating cells. In neural stem cells, elevated translation promoted self-renewal and proliferation in vitro and in vivo. Furthermore, TAPIR enabled the modeling and partial rescue of associated disease phenotypes. Our findings reveal that rRNA levels directly regulate translational output and that protein synthesis capacity can act as a key determinant of mammalian stem cell behavior.

Animals↗

PubMed2025

Oogenesis and germinal bed morphology of the brown anole (A. sagrei).

BACKGROUND: The brown anole is a model species of the genus Anolis, a squamate (encompassing lizards and snakes) group widely studied in evolutionary, behavioral, and developmental biology. Full genome annotation, the establishment of gene editing techniques, and comprehensive description of reproductive tract morphology and embryogenesis in this species, has laid the foundation for functional studies. However, analysis of brown anole oogenesis is still required and vital to optimize genome modification, mutant line establishment, and analyses of the evolution of reproductive developmental mechanisms. RESULTS: Here, we characterize ovary morphology and gametogenesis in the female brown anole, A. sagrei using brightfield imaging, microCT, histology staining, electron microscopy, and confocal imaging. We define 10 stages of oocyte maturation which commences inside the oogonial nest within the germinal bed and concludes with the mature follicle ready to ovulate based on follicle size, yolk-acquisition, and follicular, cellular, and basement membrane architecture. CONCLUSIONS: We describe the complete oogenesis of the brown anole in 10 stages and report that oogenesis is highly conserved within iguanids, a suborder of lizards. With our staging framework, we lay the foundation for functional studies of oogenesis and optimized gene-editing.

Journal Article↗

PubMed2025

Genomic evolution of EGF-CFC genes in deuterostomes.

BACKGROUND: EGF-CFC proteins are a bilaterian innovation, but they are best known for their roles in Nodal signaling during gastrulation and left-right patterning in vertebrates. Species with multiple family members show evidence of functional specialization. For example, in mouse, Cripto is required for gastrulation, whereas CFC1 is involved in left-right patterning. However, members of the EGF-CFC family across model organisms exhibit limited sequence conservation beyond the EGF-CFC domain, posing challenges for determining their evolutionary history and functional conservation. RESULTS: In this study, we describe the evolutionary history of the EGF-CFC family of proteins across several branches of deuterostomes, with a particular focus on vertebrates. We trace the EGF-CFC gene family from a single gene in the deuterostome ancestor through its expansion and functional specialization in tetrapods, and subsequent gene loss and translocation in eutherian mammals. Mouse Cripto and CFC1, zebrafish Tdgf1, and each Xenopus EGF-CFC gene (Tdgf1, Tdgf1.2 and Cripto.3) are all descendants of the ancestral deuterostome Tdgf1 gene. CONCLUSIONS: We propose that subsequent to EGF-CFC family expansion in tetrapods, Tdgf1B (Xenopus Tdgf1.2) acquired specialization in the left-right patterning cascade, and then after its translocation in eutherians to a different chromosomal location, CFC1 has maintained that specialization.

Animals↗