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 Metadata only Inflammation rewires the enteric nervous system through neurogenic monocyte recruitment(2026-03-03)Proper organization of the enteric nervous system (ENS) is critical for normal gastrointestinal (GI) physiology. Inflammatory bowel disease (IBD) disrupts key GI functions, including bowel motility. However, in many IBD patients, motility disorders persist even during remission, suggesting an irreversible ENS defect secondary to IBD. Here, we show that postinflammatory GI motility dysfunction arises from structural remodeling of the ENS, driven by a combination of neuronal loss and neurogenesis. During mucosal inflammation, enteric neurons upregulate CCL2 expression, facilitating the recruitment of monocytes into the myenteric plexus within the intestinal muscle. Monocyte-derived macrophages infiltrate the myenteric ganglia, contributing to excessive ENS remodeling and postinflammatory motility dysfunction. This neuroimmune axis is counterbalanced by a hypoxia-induced stress response in enteric neurons mediated by HIF1α. Enhancing the neuron-intrinsic hypoxia pathway limits ENS remodeling and preserves motility. In summary, this study presents a mechanistic model of postinflammatory GI motility dysfunction and proposes a therapeutic strategy to maintain ENS integrity and function during inflammation.Publication Metadata only p21-Positive Senescent Stromal Cells Promote Prostate Cancer Immune Suppression and Progression That Can Be Reversed by Senolytic Therapy(2026-03-02)Cellular senescence is a well-established tumor-suppressive cell-cycle arrest program. However, chronic inflammation through the senescence-associated secretory phenotype (SASP) can alternatively drive immune suppression and cancer progression. Using prostate cancer patient samples and murine models, we find p16+ and p21+ senescent cells accumulate throughout malignant progression and associate with immune suppression. Single-cell sequencing revealed that p16 and p21 mark distinct epithelial and stromal senescent populations, with p21+ nontumor cells expressing the highest SASP. p21+ stromal cell removal blocked the SASP to reverse immune suppression and slow tumor growth. Senolytic BCL-xL inhibitor treatment could clear p21+ stromal senescent cells, reactivating antitumor CD8+ T-cell immunity and inhibiting prostate tumor progression in mice. Suppression of BCL-xL or p21 also potentiated anti-PD-1 immune checkpoint blockade (ICB) in preclinical prostate cancer models. Our findings demonstrate that targeting p21+ senescent stromal populations can yield therapeutic benefits in advanced prostate cancer through activating antitumor immunity and enhancing immunotherapy outcomes. SIGNIFICANCE: Senescent cells accumulate in the tumor and stroma throughout prostate cancer progression and are associated with immune suppression in patients and mice. Senolytic strategies to clear p21+ senescent stromal cells can prevent prostate cancer progression and reactive cytotoxic T-cell immunity to potentiate anti-PD-1 ICB in advanced disease.Publication Open Access Genomic information increases prediction accuracy of behavior traits of Labrador Retrievers used as guide dogs(2026-03-01)BACKGROUND: This study aimed to evaluate the accuracy of prediction of breeding values in a genomic selection program for behavior traits in a population of Labrador Retrievers used as guide dogs. Implementing genomic selection as a new tool in service dogs has the potential to increase genetic gain, improving the performance of populations. Additionally, genomic predictions may help service dog organizations in identifying training candidates with higher accuracy. RESULTS: Phenotypes for 17 traits on 4,841 Labrador Retrievers collected from 2008 to 2019 from the International Working Dog Registry's (IWDR) behavior checklist were analyzed. The Behavior Checklist (BCL) standardizes a scoring system for a dog's reaction to a variety of environmental stimuli. Data are used to assess a dog's behavior and suitability for training as well as genetic selection using a selection index of prioritized traits with estimated breeding values. Genomic data were available for 1076 individuals from whole genome sequences and reduced to 94 K SNPs. Variance components were estimated using AIREML. Genomic information was included under a single-step GBLUP approach. Accuracies were evaluated among a sample of the higher accuracy animals using the linear regression method. Genomic estimates of heritability ranged from 0.08 to 0.21. Accuracies were calculated with the LR method and ranged from 0.30 to 0.58 for pedigree information, with an average of 0.46. Accuracies of genomic predictions ranged from 0.32 to 0.63, with an average of 0.50, and were higher than pedigree predictions for all traits. CONCLUSIONS: The gains in accuracy from inclusion of SNP genotype data show that genomic prediction using single-step GBLUP can improve selection by identifying the cohort of young dogs that have the highest genetic merit for the desired traits. Gains in validation accuracy were limited by the small number of genotyped animals and are expected to increase as more animals are genotyped.Publication Metadata only National Trends in Lung Cancer Stage, Treatment, and Time to Treatment Initiation After a Major Healthcare Disruption (NCDB 2014-2022)(2026-02-26)INTRODUCTION: Healthcare system (HCS) disruptions during COVID-19 have significantly impacted cancer diagnostics and treatment management. This study examined the effects of the COVID-19 pandemic on the staging at diagnosis, initial treatment patterns, and time to treatment initiation (TTI) for non-small cell lung cancer (NSCLC), focusing on disparities across healthcare settings and demographics. METHODS: We conducted a retrospective cohort analysis of NSCLC cases in the US National Cancer Database (2014-2022), excluding records with missing TTI or clinical stage data. Outcomes were compared before (2014-2019) and after (2021-2022) the healthcare system disruption using chi-square tests, t-tests, and interrupted time series analysis. RESULTS: A total of 865,808 individuals were included (mean age 69; 50% female; 82% White; 73% Medicare/Medicaid). Early-stage diagnoses increased from 44% to 46% (p<0.01). Minor differences were observed in initial treatment patterns. Mean TTI increased by approximately 9 days (p<0.01), with community cancer programs showing the greatest increase (+10 days) compared to other facilities. Regional differences were also noted, with New England experiencing the highest TTI increase (+12 days). Black individuals faced longer TTIs (56 vs 51 days for White patients), though White patients experienced the greatest increased (+9 days). CONCLUSIONS: Healthcare system disruptions due to COVID-19 were associated with delayed NSCLC diagnoses, longer treatment initiation, and persistent disparities in access to timely care. While short-term survival differences were modest, earlier treatment initiation remained associated with improved outcomes. Further research is needed to evaluate whether these delays persist and to explore their long-term consequences on patient outcomes. POLICY SUMMARY: This evidence calls for resilience-focused oncology policies, supporting continuity plans, real-time delay monitoring, and targeted resource allocation to underserved and outpatient settings.