Biology subjects

Overbey, E.

Publications and source records attributed to Overbey, E..

2 recordsLinked to original sources

bioRxiv2024

Pharmacogenomics Guided Spaceflight: the intersection between space-flown drugs and space genes

Ten years ago, it was predicted that the multi-omics revolution would also revolutionize space pharmacogenomics. Current barriers related to the findable, accessible, interoperable, and reproducible use of space-flown pharmaceutical data have contributed to a lack of progress beyond application of earth-based principles. To directly tackle these challenges, we have produced a novel database of all the drugs flown into space, compiled from publicly available ontological and spaceflight-related datasets, to exemplify analyses for describing significant spaceflight-related targets. By focusing on mechanisms perturbed by spaceflight, we have provided a novel avenue for identifying the most relevant changes within the drug absorption, distribution, metabolism, and excretion pathways. We suggest a set of space genes, by necessity limited to available tissue types, that can be expanded and modified based on future tissue-specific and mechanistic-specific high-throughput assays. In sum, we provide the justification and a definitive starting point for pharmacogenomics guided spaceflight as a foundation of precision medicine, which will enable long-term human habitation of the Moon, Mars, and beyond. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/575951v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@48f739org.highwire.dtl.DTLVardef@5ecdb0org.highwire.dtl.DTLVardef@121c93org.highwire.dtl.DTLVardef@1122b3f_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2017

Aligning single-cell developmental and reprogramming trajectories identifies molecular determinants of reprogramming outcome

Cellular reprogramming through manipulation of defined factors holds great promise for large-scale production of cell types needed for use in therapy, as well as for expanding our understanding of the general principles of gene regulation. MYOD-mediated myogenic reprogramming, which converts many cell types into contractile myotubes, remains one of the best characterized model system for direct conversion by defined factors. However, why MYOD can efficiently convert some cell types into myotubes but not others remains poorly understood. Here, we analyze MYOD-mediated reprogramming of human fibroblasts at pseudotemporal resolution using single-cell RNA-Seq. Successfully reprogrammed cells navigate a trajectory with two branches that correspond to two barriers to reprogramming, with cells that select incorrect branches terminating at aberrant or incomplete reprogramming outcomes. Differential analysis of the major branch points alongside alignment of the successful reprogramming path to a primary myoblast trajectory revealed Insulin and BMP signaling as crucial molecular determinants of an individual cells reprogramming outcome, that when appropriately modulated, increased efficiency more than five-fold. Our single-cell analysis reveals that MYOD is sufficient to reprogram cells only when the extracellular milieu is favorable, supporting MYOD with upstream signaling pathways that drive normal myogenesis in development.

genomics↗