eScholarship@UMassChan
eScholarship@UMassChan is a digital archive for UMass Chan Medical School's research and scholarship, including journal articles, theses, datasets and more. We welcome submissions from our faculty, staff, and students. eScholarship@UMassChan is a service of the Lamar Soutter Library, Worcester, MA, USA. See also our open access journal publishing services.
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Recent Publications
Publication Biofilm Heterogeneity in Bacillus subtilis(UMass Chan Medical School, 2025-09-29)Bacteria are found throughout the world, in environments ranging from water to soil to the human gut. One survival mechanism common to all these environments is the formation of biofilms – communities of microorganisms encased in self-produced extracellular matrices. Biofilms are important because they provide a protective, extracellular structure that allows cells to specialize. Specialization can be either inter-species, where a certain species fills a niche; or intra-species, where genetically identical cells metabolically differentiate to fill niches within the biofilm community. To study intra-species differentiation, I use the model organism Bacillus subtilis, a soil-borne bacterium known to differentiate into numerous, phenotypically distinct cell types. In this thesis, I characterize the spatial-, temporal- and media-specific differences of gene expression in B. subtilis NCIB3610 using fluorescent transcriptional reporters, top-down colony images, biofilm cross-sectioning, and flow cytometry. As part of this work, I extended the use of Gaussian mixture models to analyze bacterial flow cytometry data and show how this approach provides insights into expression patterns that are obscured when simple on-off gates are applied. Altogether, these data demonstrate that cellular transcriptional heterogeneity within these biofilms is even more extensive than previously understood. My data provide a framework for generating hypotheses about how this heterogeneity is established and maintained. In addition, I propose and test whether DNA methylation acts as a control mechanism for driving biofilm heterogeneity in B. subtilis biofilms. My data indicate that although there are phenotypic differences between strains where putative DNA methyltransferases have been deleted, none appear to drive differences in detectable DNA methylation. Overall, my work extends our understanding of bacterial cellular heterogeneity and provides analysis tools and new hypotheses for future work.Publication An Emerging Long Non‐coding RNA Regulates Synaptogenesis in Drosophila(UMass Chan Medical School, 2025-08-23)It is widely accepted that synaptogenesis and synaptic plasticity are the foundation of learning and memory and is implicated in many neurological and psychiatric diseases. Our lab previously described the ViSyToR (Viral Synaptic Transfer of RNA) pathway required for synaptogenesis at the Drosophila larval neuromuscular junction (NMJ), which involves two key components: darc1, a retrotransposon-like capsid gene, and copia, a retrotransposon. Both dArc1 and Copia proteins form capsid-like structures, bind to their own RNAs, and are transferred across the NMJ from presynaptic neurons to postsynaptic muscles. dArc1 is a positive regulator of synaptogenesis, while Copia is a negative regulator of synaptogenesis. They compete to maintain the proper synaptic growth at the NMJ. Using RNA immunoprecipitation, we found that the long non-coding RNA statera (stae, originally CR34335) associates with Copia proteins. stae is highly expressed in neurons and muscles of Drosophila. stae mutants show a decrease of bouton numbers at the NMJ, suggesting that stae is a positive regulator of synaptogenesis. Strikingly, stae knockout leads to upregulation of copia expression, with an increase of copia RNA stability and transposition activity, suggesting that stae is a repressor of copia elements. We further showed by bioinformatic analysis that stae is an emerging lncRNA during Drosophila evolution. Taken together, our results point to an unexpected role of a long non-coding RNA in regulating synaptogenesis by repressing a retrotransposon.Publication Publication A Pilot Pragmatic Cluster Randomized Trial of School-Supervised Therapy to Improve Pediatric Asthma Control(2025-08-22)Background: Although school-supervised inhaled corticosteroid administration has potential to improve asthma morbidity, there has yet to be an evaluation of the pediatric practice as a setting to identify children with asthma and connect them to school-supervised asthma therapy. Objective: Conduct a pragmatic pilot trial of Asthma Link, a model that connects children with asthma seen in pediatric practice to supervised asthma therapy in the school setting. Methods: Four pediatric practices were pair-matched and randomized to (1) Asthma Link plus an asthma educational workbook or (2) Enhanced Usual Care, the same workbook alone. We recruited children 6 to 17 years old with poorly controlled asthma, prescribed a daily inhaled corticosteroid. Parent-child dyads completed surveys at baseline and 3, 6, and 12 months. Primary outcomes: recruitment/retention of pediatric practices and parent-child dyads and intervention fidelity. Secondary outcomes: asthma symptoms, medication adherence, emergency room visits, hospital admissions, oral steroid use, missed schooldays. Results: Four pediatric practices and 66 parent-child dyads were recruited (average child age 9 y, 44% female, 65% Hispanic, 23% Black, 62% low income). All (4 of 4) practices were retained throughout the study and retention of parent-child dyads was 95%, 91%, and 89% at 3, 6, and 12 months, respectively. All (31 of 31) Asthma Link families brought their child's preventive inhaler into school; children received school health staff-supervised therapy on more than 95% of schooldays over 12 months. Children in the Asthma Link group had greater improvement in Asthma Control Test scores, longer time to first asthma exacerbation, less oral steroid use, and better medication adherence compared with the Enhanced Usual Care group. Conclusions: Extending the reach of pediatric practices to facilitate the delivery of daily asthma prevention medication at school was feasible and improved pediatric asthma morbidity.Publication Safety and efficacy of preoperative embolization in the treatment of brain arteriovenous malformations with perinidal aneurysms and single draining vein: a multicenter study with propensity score-weighting(2025-08-22)Background and objectives: Arteriovenous malformations (AVMs) with perinidal aneurysms and single draining vein are associated with an elevated risk of rupture and increased procedural complexity. The role of preoperative embolization in this high-risk anatomical subset remains unclear. This study aimed to evaluate the safety and efficacy of microsurgery with preoperative embolization, compared with microsurgery alone in patients with such AVMs. Methods: We conducted a multicenter retrospective analysis of an AVM registry from the MISTA (Multicenter International Study for Treatment of Brain AVMs) consortium and included AVMs with perinidal aneurysms and a single draining vein. Baseline characteristics, angiographic outcomes, functional outcomes, and complication rates were compared. Propensity score weighting (PSW) using the covariate balancing method was applied to adjust for baseline differences. Results: Out of a total of 1919 patients, 65 met the inclusion criteria; 45 patients underwent preoperative embolization followed by microsurgery, and 20 underwent microsurgery alone. After adjustment, complete obliteration rates were similar between groups (OR 0.87, 95% CI 0.04 to 16.33, P=0.92), as were rates of functional independence at discharge and follow-up. Overall complication, symptomatic complication, and mortality rates did not differ significantly between groups. However, permanent complications were significantly lower in patients with preoperative embolization (OR 0.06, 95% CI 0.004 to 0.84, P=0.03). Discussion: In patients with AVMs featuring perinidal aneurysms and single draining vein, preoperative embolization followed by microsurgery was associated with fewer permanent complications and no increase in adverse outcomes compared with microsurgery alone. However, given the small number of events, this finding should be interpreted cautiously.