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Henson, M.

Publications and source records attributed to Henson, M..

4 recordsLinked to original sources

Longitudinal single-cell and spatial transcriptomics reveals intratumor heterogeneity, therapeutic response, and comparative value of canine marginal zone lymphoma

Diffuse B-cell lymphomas are the most prevalent canine hematologic malignancies, and their clinical presentation resembles that of human B-cell non-Hodgkin lymphomas (NHLs). However, a lack of a clear subtyping framework perpetuates imprecise treatment approaches that fail to address mechanisms of therapy resistance. Here, we employed deep phenotyping via serial sampling and longitudinal transcriptomics to evaluate intratumoral composition and therapy response in a 6-year-old neutered male goldendoodle with stage 5A marginal zone lymphoma (MZL). Following sequential treatment consisting of a single IV dose of oncolytic vesicular stomatitis virotherapy (VSV) and standard CHOP chemotherapy 30 days later, we performed scRNAseq on seven serial lymph node biopsies and spatial sequencing on a resection taken 10 days post-VSV treatment. B cells (>90%) comprised three transcriptionally distinct and temporally stable subpopulations, with specific copy number profiles and robust spatial organization despite disrupted lymph node architecture. Analysis across subpopulations revealed downregulation of the quiescence program including KLF2, suggesting similarity to KLF2-deficient human MZL. While VSV successfully reached target B cells, downstream transcriptional responses were predominantly localized to the T-cell compartment. T cells ([≤]6%) showed increased proliferation and upregulation of cytotoxicity markers post-VSV administration, enriching for leukocyte-mediated cytotoxicity pathways consistent with an anti-viral immune response. Ultimately, these results provide an in vivo proof-of-concept for the treatment paradigm in canine lymphoma, while emphasizing the need for improved subtyping frameworks and multidimensional treatment strategies targeting intratumoral heterogeneity.

cancer biology↗

Host-independent persistence of the Diadema antillarum Scuticociliatosis Philaster clade in coastal environments

The mass mortality of the keystone herbivore Diadema antillarum in the Caribbean was caused by the pathogenic ciliate from the Diadema antillarum Scuticociliatosis Philaster clade (DaScPc). Despite its confirmed pathogenicity, the environmental distribution and persistence strategies of DaScPc outside its host remain poorly understood. We used quantitative PCR, nested PCR, and Sanger sequencing across a 16-month time series and broad geographic surveys to investigate its ecological dynamics and potential environmental reservoirs. Sequencing-confirmed detections at a Florida coastal site devoid of D. antillarum show that DaScPc is a natural, host-independent component of the reef environment. Molecular detection on coral and macroalgal surfaces and in the plankton fraction indicates that multiple substrates can harbor the ciliate. Temporal observations revealed emerging trends with macroalgal cover and reef productivity, though no direct correlations were observed. Geographically, DaScPc was absent from outbreak sites in Panama and Reunion. Together, this data suggests spatial patchiness and a cryptic "boom-and-bust" lifestyle in which the organism persists at low abundance between outbreaks. The co-occurrence of a related nonpathogenic ciliate (Acropora/CHN/2009) further underscores the ecological complexity of the Philaster clade. These findings broaden understanding of DaScPc ecology, confirming environmental persistence independent of its host and suggesting that parasitism may be intermittent, triggered by changing environmental conditions. This work highlights the need for higher-resolution surveillance and long-term monitoring to link ecosystem processes with the reemergence of marine disease in vulnerable coral reef systems. ImportanceThe 2022 mass mortality of the sea urchin Diadema antillarum devastated Caribbean coral reefs, yet little is known about how the pathogenic ciliate responsible for the event persists in nature. We show that the Diadema antillarum Scuticociliatosis Philaster clade (DaScPc) occurs in reef environments even where the host (D. antillarum) is absent, indicating that it can persist independently of its host. Our findings suggest that DaScPc occupies a cryptic ecological niche within reef microbial communities and may follow a "boom-bust" dynamic, fluctuating between rare environmental states and occasional proliferation. Although direct environmental drivers remain unresolved, emerging trends with macroalgal cover and reef productivity highlight the potential influence of ecosystem conditions on ciliate abundance. This work broadens the understanding of how marine pathogens persist between outbreaks and underscores the importance of environmental surveillance for predicting and mitigating future disease events on coral reefs.

microbiology↗

Ecophysiology of the cosmopolitan OM252 bacterioplankton (Gammaproteobacteria)

Among the thousands of species that comprise marine bacterioplankton communities, most remain functionally obscure. One key cosmopolitan group in this understudied majority is the OM252 clade of Gammaproteobacteria. Although frequently found in sequence data and even previously cultured, the diversity, metabolic potential, physiology, and distribution of this clade has not been thoroughly investigated. Here we examined these features of OM252 bacterioplankton using a newly isolated strain and genomes from publicly available databases. We demonstrated that this group constitutes a globally distributed novel genus (Candidatus Halomarinus), sister to Litoricola, comprising two subclades and multiple distinct species. OM252 organisms have small genomes (median 2.21 Mbp) and are predicted obligate aerobes capable of alternating between chemoorganoheterotrophic and chemolithotrophic growth using reduced sulfur compounds as electron donors, with subclade I genomes encoding the Calvin-Benson-Bassham cycle for carbon fixation. One representative strain of subclade I, LSUCC0096, had extensive halotolerance but a mesophilic temperature range for growth, with a maximum of 0.36 doublings/hr at 35{degrees}C. Cells were curved rod/spirillum-shaped, ~1.5 x 0.2 m. Growth on thiosulfate as the sole electron donor under autotrophic conditions was roughly one third that of heterotrophic growth, even though calculations indicated similar Gibbs energies for both catabolisms. These phenotypic data show that some Ca. Halomarinus organisms can switch between serving as carbon sources or sinks and indicate the likely anabolic cost of lithoautotrophic growth. Our results thus provide new hypotheses about the roles of these organisms in global biogeochemical cycling of carbon and sulfur. ImportanceMarine microbial communities are teeming with understudied taxa due to the sheer numbers of species in any given sample of seawater. One group, the OM252 clade of Gammaproteobacteria, has been identified in gene surveys from myriad locations, and one isolated organism has even been genome sequenced (HIMB30). However, further study of these organisms has not occurred. Using another isolated representative (strain LSUCC0096) and publicly available genome sequences from metagenomic and single-cell genomic datasets, we examined the diversity within the OM252 clade, the distribution of these taxa in the worlds oceans, reconstructed the predicted metabolism of the group, and quantified growth dynamics in LSUCC0096. Our results generate new knowledge about the previously enigmatic OM252 clade and point towards the importance of facultative chemolithoautotrophy for supporting some clades of ostensibly "heterotrophic" taxa.

microbiology↗

Pseudomonas aeruginosa reverse diauxie is an optimized, resource utilization strategy

Pseudomonas aeruginosa is a globally-distributed bacterium often found in medical infections. The opportunistic pathogen uses a different, carbon catabolite repression (CCR) strategy than many, model microorganisms. It does not utilize a classic diauxie phenotype, nor does it follow common systems biology assumptions including preferential consumption of glucose with an overflow metabolism. Despite these contradictions, P. aeruginosa is competitive in many, disparate environments underscoring knowledge gaps in microbial ecology and systems biology. Physiological, omics, and in silico analyses were used to quantify the P. aeruginosa CCR strategy known as reverse diauxie. An ecological basis of reverse diauxie was identified using a genome-scale, metabolic model interrogated with in vitro omics data. Reverse diauxie preference for lower energy, nonfermentable carbon sources, such as acetate or succinate over glucose, was predicted using a multidimensional strategy which minimized resource investment into central metabolism while completely oxidizing substrates. Application of a common, in silico optimization criterion, which maximizes growth rate, did not predict the reverse diauxie phenotypes. This study quantifies P. aeruginosa metabolic strategies foundational to its wide distribution and virulence.

systems biology↗