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 Embargo MS4A6A is a Key Regulator of Myeloid Cell Activation in MS and Neuroinflammation(UMass Chan Medical School, 2026-04-15)Multiple Sclerosis (MS) is a devastating, incurable neurodegenerative disease affecting 3 million individuals globally. There remains an especially strong need for elucidating mechanisms of chronic inflammation in MS. I explored whether MS4A6A and its murine orthologue Ms4a6c, genes known to regulate CNS macrophages, could modulate the neuroimmune response in MS. I found that MS4A6A was strongly upregulated in macrophages from MS patient lesions. I then investigated the effect of Ms4a6c-knock-out (6C-KO) on the EAE model of MS. I found that 6C-KO mice had partial mitigation of paralysis and brain T-cell infiltration, but a nearly complete reversion of microglial inflammation and activation. This MS4A-dependent microglial phenotype was recapitulated in humanized MS4A6A-knock-in versus 6A-KO EAE mice. I performed adoptive transfer of cells from EAE donors into naïve recipients and found a large effect of donor genotype on clinical severity, suggesting Ms4a6c may modulate the ability of peripheral monocytes to induce antigen-reactive T-cells. There was also a donor-independent effect of genotype on microglial activation, indicating a distinct CNS-specific role of Ms4a6c in microglia. To investigate this, I employed the Cuprizone model of oligodendrocyte toxicity and found that 6C-KO mice had reduced microglial activation and demyelination. I also found that 6C-KO microglia phagocytosed significantly less myelin in vitro. Lastly, I showed that Ms4a6c and MS4A6A both regulate ligand-mediated microglial calcium influx, identifying a putative mechanism by which these genes modulate activation. Together, these findings indicate MS4A6A as a key regulator of peripheral and CNS-resident macrophage activation, and as a promising therapeutic target in MS.Publication Embargo Integration of Eubiotic Signaling via the Unfolded Protein Response Regulates P-glycoprotein Expression and Colonic Homeostasis(UMass Chan Medical School, 2026-04-14)The intestinal epithelium integrates signals from a healthy microbiome to coordinate homeostatic responses, including restraining transepithelial neutrophil migration through eubiotic maintenance of P-glycoprotein (P-gp) levels. P-gp secretes endocannabinoids into the intestinal lumen, establishing a lipid gradient that restricts neutrophil migration. In this project, I sought to characterize the microbial signals sensed by the epithelium and to identify the mechanisms by which intestinal epithelial cells respond by maintaining high expression of P-gp. I mapped the taxonomic associations, microbial interactions, and metabolic networks that induce P-gp and developed a model to predict P-gp induction by defined microbial consortia. I further identified the unfolded protein response (UPR) as a novel signal-integration platform linking microbial metabolites to epithelial P-gp expression. Beyond its canonical role in responding to cellular stress, the UPR interprets diverse microbial-derived metabolic cues and responds by promoting P-gp expression. Both butyrate and secondary bile acids activate two complementary phospholipid-modifying pathways, producing shifts in the composition and dynamics of the endoplasmic reticulum membrane that activate ER stress sensors and initiate the UPR. This signaling cascade culminates in direct binding of ATF3 to the ABCB1 locus, inducing P-gp expression. Together these findings define the communication pathway through which eubiotic metabolites are sensed by the intestinal epithelium to regulate neutrophil migratory tone. Our results suggest that in the colon canonical stress pathways may have adapted to also serve as sensors of luminal homeostasis, allowing epithelial cells to respond to eubiosis by maintaining high expression of P-gp and thus guard against aberrant neutrophil migration.Publication Open Access A lifeline on wheels: perspectives of stakeholders on the implementation and impact of a mobile medications for opioid use disorder unit(2026-04-11)INTRODUCTION: Mobile health units (MHUs) providing medications for opioid use disorder (MOUD) have emerged as a critical strategy to address gaps in opioid treatment access, particularly for marginalized populations. Research has yet to explore stakeholder perspectives on MHUs' implementation, challenges, and long-term sustainability. METHODS: We conducted semi-structured interviews with 15 stakeholders, including MHU staff, administrators, community partners, and policymakers. Interviews explored experiences with the MHU, barriers and facilitators to patient engagement, and operational challenges. Data were transcribed, coded, and analyzed using a template thematic approach to identify key themes related to implementation and sustainability. RESULTS: Stakeholders endorsed the MHU as a highly accessible and flexible intervention that reduces barriers for people experiencing homelessness, economic instability, and transportation limitations. The MHU facilitated strong patient-provider relationships and access to harm reduction, primary care, and social services. Challenges included staffing shortages, inconsistent funding, limited clinical space, and environmental barriers. Additionally, stigma, political resistance, and law enforcement interactions affected service delivery and patient engagement. DISCUSSION: Findings highlight the importance of policy and funding mechanisms to ensure the long-term viability of MHUs. Stakeholders recommended expanding outreach, increasing staffing, and integrating additional services. Addressing these challenges is essential to sustaining MHUs as an effective public health intervention for opioid use disorder.Publication Metadata only Bridging Systems of Care: Experiences of Faith Leaders Supporting Community Mental Health in Worcester, Massachusetts(2026-04-11)Amid ongoing workforce shortages in primary and mental healthcare, faith leaders play an important role in supporting individuals with mental health concerns, particularly in culturally diverse urban settings. We conducted semi-structured interviews with 13 faith leaders from diverse religious backgrounds in Worcester, Massachusetts. Interviews explored understandings of mental health, approaches to supporting congregants, and interactions with the healthcare system. Data was analyzed using thematic analysis. Four major themes emerged: (1) faith leaders are approached for a breadth of mental health concerns which are understood to be multifactorial; (2) faith leaders are accessible and complementary resources; (3) faith leaders are vulnerable to burnout; and (4) collaboration with the health system is limited and inconsistent. Ulti- mately, we describe that faith leaders offer accessible, comprehensive, longitudinal, and coordinated mental health support, though encounter significant challenges including outdated referral resources, lack of formal training, emotional burden, and inconsistent engagement from healthcare systems. Strengthening collaboration through faith leader training programs, updated referral pathways, shared dialogue spaces, and improved cultural and religious competency among clinicians has the potential to improve community mental health by targeting specific, modifiable barriers identified by faith leaders.Publication Open Access New approaches to discovering epigenetic rules of homeostasis in diverse mammal species(2026-04-10)Background: While the cells of some mammals, such as humans, maintain their internal5 temperature within tightly controlled ranges, the cells of others, such as dromedary camels,6 experience wide ranges of temperature variation. In order to understand these differences, it7 is critical to identify differentially expressed genes (DEGs) and their interactions; however,8 the data available are often insufficient to obtain statistically significant results.9 Results: We develop an explanatory model to understand the mechanisms of response of10 mammalian species to environmental perturbation on the basis of empirical gene expression11 data. Our approach is motivated by the novel idea that approximately preserved or reduced12 inter-individual variability of expression levels upon environmental change is an indicator13 that a given gene contributes to a homeostasis-preserving mechanism for the species. To14 identify such genes, we use a simple non-statistical criterion that is suitable even when the15 number of replicates is limited. We then identify four extreme subgroups of the DEGs,16 and from these construct an intuitive neural network architecture that best interpolates17 the data and describes the principal response rules of the considered species. Finally, we18 propose measures of the robustness of homeostasis (well-being) from these networks based19 on perturbation analysis and entropy computations. The data used to develop the model20 were collected from homogeneous cell cultures of skin fibroblasts.21 Conclusions: Even with data available for just a few individuals, our model identi-22 fies extreme response sets of genes, using inter-individual variability to provide a faithful23 representation of the response of the species to environmental perturbations. Sets of genes24 identified as relevant in individual species are useful for comparing responses across species.25 All the measures of cellular well-being introduced in this work rank camels higher than26 humans for both the 32° and 41° treatments.