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 Open Access Vocational Rehabilitation Services Positively Impacting the Employment Outcomes of People with Disabilities(UMass Chan Medical School, 2026-02-10)A systematic scoping review of research published between 2000 and 2020 on employment of people with disabilities, that was funded by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR), was conducted by CeKTER (NIDILRR Grant #90DPEM0004, 2020–2025) researchers. All papers comparing people with disabilities to those without were excluded from the systematic scoping review. Among over 100 publications reviewed there was a wide and very disparate array of findings with numerous variables used and varying research questions. This result belies summative findings. There are numerous ways of organizing the disparate findings. This brief is part of a series of findings from the center’s systematic scoping review. In this brief we report on findings about specific vocational rehabilitation services positively impacting the employment of people with disabilities. Please note that all comparisons are always about corresponding peers with disabilities.Publication Open Access A randomized, double-blind, placebo-controlled study of losmapimod in patients with facioscapulohumeral muscular dystrophy: Results of the REACH study(2026-02-06)BACKGROUND: Losmapimod is an orally administered small molecule and selective p38α/β mitogen-activated protein kinase (MAPK) inhibitor able to reduce aberrant expression of and thereby potentially slowing disease progression in patients with facioscapulohumeral muscular dystrophy (FSHD). OBJECTIVE: This global, randomized, placebo-controlled, double-blind phase 3 study in patients with FSHD1 and FSHD2 examined the efficacy and safety of losmapimod over a 48-week treatment period compared to placebo (NCT05397470, EUDRACT 2022-000389-16). METHODS: The primary endpoint was change in quantification of reachable workspace (RWS) expressed as relative surface area (RSA). Other endpoints included measures of muscle composition (fat content and lean muscle) using magnetic resonance imaging (MRI), muscle strength using quantitative dynamometry, and quality of life measures. RESULTS: 130 participants received losmapimod and 130 participants received placebo, with 252 participants completing the 48-week treatment period. There were no statistically significant differences between groups in change in RSA and all secondary efficacy endpoints from baseline to Week 48. Losmapimod treatment was well-tolerated, and most adverse events were mild. CONCLUSIONS: Losmapimod was generally well tolerated with a favorable safety profile at a dose of 15 mg twice daily. Although none of the efficacy endpoints were met, study design and data from the study may inform future studies of FSHD therapies.Publication Metadata only Cohesin-mediated chromatin organization controls the differentiation and function of dendritic cells(2026-02-06)The cohesin complex extrudes chromatin loops, stopping at sites bound by CCCTC-binding factor (CTCF) and organizing chromosomes into topologically associated domains, yet biological implications of this process remain obscure. We show that cohesin controls the in vivo differentiation and function of murine antigen-presenting dendritic cells (DCs), particularly antigen cross-presentation and interleukin-12 (IL-12) secretion by type 1 conventional DCs (cDC1s). The chromatin organization of DCs was shaped by cohesin and the transcription factor IRF8, which facilitated chromatin looping and chromosome compartmentalization, respectively. Optimal expression of IRF8 itself required CTCF/cohesin binding sites demarcating the gene. During DC activation, cohesin enabled the induction of a subset of genes that were preferentially located in Polycomb-repressed regions and enriched in more distal enhancers. Accordingly, deletion of CTCF sites flanking the gene in mice reduced IL-12 production by cDC1s. Our data reveal an essential role of cohesin-mediated chromatin folding in cell differentiation and function in vivo and its bidirectional cross-talk with lineage-specifying transcription factors.Publication Embargo Characterization of CD8+ T cell Subpopulations and the Role of CD137 in Vitiligo(UMass Chan Medical School, 2026-02-03)Vitiligo is an autoimmune disease in which CD8+ T cells selectively kill melanocytes, leading to skin depigmentation. Single-cell RNA sequencing (scRNA-seq) studies have profiled these T cells at the population level, but subpopulation characterization remains to be done. We aimed to determine the different subpopulations of CD8+ T cells in vitiligo-lesional skin and assess whether these populations differed in their clonal landscapes and spatial distributions. With this knowledge, we hoped to differentiate effector from bystander CD8+ T cells and pinpoint the effector programs driving T cell activation at sites of inflammation to develop new cell-targeted immunotherapies. To answer these questions, we combined scRNA/TCR-seq with spatial transcriptomics on vitiligo skin biopsies and performed functional experiments in vitro and in vivo. We identified four transcriptionally distinct subpopulations and focused on one population that stood out as clonally expanded and autoreactive. These CD8+ T cells infiltrate the skin throughout the body of vitiligo patients, migrate to the epidermis, and upregulate TNFRSF9 when in contact with melanocytes. During melanocyte engagement, this population coexpresses CD137/CD137L, providing a mechanism for self-stimulation. Human and mouse in vitro experiments determined that CD137 expression is required for optimal effector function, while CD137 knockout CD8+ T cells and CD137 antagonism significantly reduced disease and prevented effector retention within the skin in a mouse model of vitiligo. We also observed similar results in a mouse model of experimental autoimmune encephalomyelitis. Together, our results nominate CD137 blockade as a promising therapeutic for vitiligo and other cytotoxic T cell-driven autoimmune diseases.Publication Open Access Associations between historical redlining and BMI: Potential indirect pathways through neighborhood socioeconomic and environment factors and their associated lifestyle behaviors in CARDIA(2026-02-03)It is unknown whether living in neighborhoods historically rated as "high-risk" mortgage by lenders (i.e., "redlining") defined by maps of the Home Owners' Loan Corporation (HOLC) neighborhood ratings may associate with obesity through neighborhood factors and health behaviors, or how such associations might differ by race and gender. We used data from the 1985-86 Coronary Artery Risk Development in Young Adults (CARDIA) study to test whether retrospective cohort associations between redlining and body mass index (BMI) were mediated by paths from census-derived social and economic neighborhood factors, food availability, physical activity (PA) resources to diet and physical activity behaviors. We found that the HOLC ratings (which reflected institutionalized racial sentiment of the time) were associated with higher levels of neighborhood socioeconomic deprivation within all racial and gender groups. For White adults and men, historically redlined neighborhoods were indirectly associated with higher BMI through neighborhood socioeconomic deprivation and lower diet quality. An indirect pathway connecting redlining to BMI was also identified for Black adults, but higher quality diet correlated with higher BMI. While women's dietary quality was not associated with BMI, redlining was directly associated with neighborhood socioeconomic deprivation which was directly associated with higher BMI and lower dietary quality, separately. Food and PA resource availability were inconsistently associated with HOLC ratings. Overall, historically redlined neighborhoods remained socioeconomically deprived 50 years later, which may have contributed to lower diet quality for all race and gender groups. The historic intertwining of race and value, as illustrated by the redlining maps, may have influenced disparities in BMI across race and gender groups. This suggests complex interactions among redlining, race, gender, and BMI.