Biology subjects

Putman, R.

Publications and source records attributed to Putman, R..

4 recordsLinked to original sources

bioRxiv2026

Phylogenomic Characterization of Two Alternaria Lineages Associated with Cotton Leaf Spot in Tennessee

Alternaria leaf spot is an important foliar disease of cotton (Gossypium hirsutum L.) and has historically been associated primarily with Alternaria macrospora in the United States. In November 2025, symptomatic Upland cotton leaves from a research greenhouse at Tennessee Technological University's Oakley Farm in Livingston, Tennessee, yielded two Alternaria isolates, 2-2 and 9-1. Quantitative conidial characterization showed substantial overlap in dimensions, septation, and shape. Concatenated ITS-RPB2 phylogenetic analysis supported different broad affinities, placing isolate 2-2 within an A. alternata- dominated group and isolate 9-1 within a group associated with the A. arborescens species complex (AASC), although their immediate relationships were weakly resolved. Phylogenomic analysis of 1,501 single-copy BUSCO orthologs from 63 genomes placed isolate 2-2 within the A. alternata lineage, sister to BMP2343, and isolate 9-1 within the AASC, sister to MOD1-FUNGI6. In controlled pathogenicity assays, isolate 9-1 reproduced foliar lesions on cotton, whereas mock-inoculated plants remained symptomless, and molecularly confirmed re-isolation fulfilled Koch's postulates. Isolate 2-2 produced insufficient conidia under the culture conditions used to prepare a standardized inoculum, and its pathogenicity was therefore not determined. These results reveal phylogenetically distinct Alternaria lineages associated with symptomatic cotton and establish an AASC isolate as a causal agent of cotton leaf spot in Tennessee.

pathology↗

bioRxiv2024

Systemic in utero gene editing as a treatment for cystic fibrosis

In utero gene editing has the potential to modify disease causing genes in multiple developing tissues before birth, possibly allowing for normal organ development, disease improvement, and conceivably, cure. In cystic fibrosis (CF), a disease that arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, there are signs of multiorgan disease affecting the function of the respiratory, gastrointestinal, and reproductive systems already present at birth. Thus, treating CF patients early is crucial for preventing or delaying irreversible organ damage. Here we demonstrate proof-of-concept of multiorgan mutation correction in CF using peptide nucleic acids (PNAs) encapsulated in polymeric nanoparticles and delivered systemically in utero. In utero editing was associated with sustained postnatal CFTR activity, at a level similar to that of wild-type mice, in both respiratory and gastrointestinal tissue, without detection of off-target mutations in partially homologous loci. This work suggests that systemic in utero gene editing represents a viable strategy for treating monogenic diseases before birth that impact multiple tissue types.

bioengineering↗

bioRxiv2022

In vivo correction of cystic fibrosis mediated by PNA nanoparticles

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We sought to correct the multiple organ dysfunction of the F508del CF-causing mutation using systemic delivery of peptide nucleic acid gene editing technology mediated by biocompatible polymeric nanoparticles. We confirmed phenotypic and genotypic modification in vitro in primary nasal epithelial cells from F508del mice grown at air-liquid interface and in vivo in F508del mice following intravenous delivery. In vivo treatment resulted in a partial gain of CFTR function in epithelia as measured by in situ potential differences and Ussing chamber assays and correction of CFTR in both airway and GI tissues with no off-target effects above background. This is the first report of systemic gene editing for CF. Our data suggest that systemic delivery of PNA NPs designed to correct CF-causing mutations is a viable option to ameliorate the disease in multiple affected organs.

bioengineering↗

bioRxiv2019

Nanoparticle delivery of microRNA-146a regulates mechanotransduction in lung macrophages and mitigates lung injury during mechanical ventilation

During mechanical ventilation, injurious biophysical forces exacerbate lung injury. These forces disrupt alveolar capillary barrier integrity, trigger proinflammatory mediator release, and differentially regulate genes and non-coding oligonucleotides such as microRNAs. In this study, we identify miR-146a as a mechanosensitive microRNA in alveolar macrophages that has therapeutic potential to mitigate lung injury during mechanical ventilation. We used humanized in-vitro systems, mouse models, and biospecimens from mechanically ventilated patients to elucidate the expression dynamics of miR-146a that might be required to decrease lung injury during mechanical ventilation. We found that the endogenous increase in miR-146a following injurious was relatively modest and not sufficient to prevent lung injury. However, when miR-146a was highly overexpressed using a nanoparticle-based delivery platform in vivo, it was sufficient to prevent lung injury. These data indicate that the endogenous increase in microRNA-146a during MV is a compensatory response that only partially limits VILI and that nanoparticle delivery approaches that significantly over-express microRNA-146a in AMs is an effective strategy for mitigating VILI.

molecular biology↗