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 Engineered Nme2Cas9 Adenine Base Editors to Treat Rett Syndrome(UMass Chan Medical School, 2025-05-13)Rett syndrome (RTT) is a severe X-linked progressive neurodevelopmental disorder that primarily affects females in early childhood. Although the FDA has approved the first drug treatment for RTT, no curative therapy is currently available. Precision genome editing technologies—particularly CRISPR-based adenine base editing (ABE)—offer a promising strategy for the permanent correction of pathogenic MECP2 mutations, the primary genetic cause of RTT. This thesis explores the use of an imperfect guide RNA (igRNA) strategy incorporating internal barcodes to reduce bystander editing while maintaining high on-target editing efficiency. The approach demonstrated robust editing performance and laid the groundwork for validation in patient-derived fibroblasts and relevant mouse models. These findings highlight a potentially curative genome editing strategy for RTT that can be extended to several of the most prevalent MECP2 mutations. Furthermore, this work supports the broader application of compact ABEs for the treatment of additional central nervous system (CNS) disorders.Publication Improving Women Veterans’ Experience of Obstetric Care in the United States: Findings From a Mixed-Methods Analysis of VA-Purchased Maternity Care(UMass Chan Medical School, 2025-05-12)Introduction: Women Veterans represent a growing and medically complex population within the U.S. healthcare system, yet their experiences with maternity care—especially when delivered outside the VA through Community Care Network (CCN) providers—remain under-examined. This dissertation: (1) investigates racial and ethnic disparities in obstetric outcomes, (2) evaluates a community-based doula intervention, and (3) explores how Black, Indigenous, and People of Color (BIPOC) Veterans navigate provider selection and engage with perinatal care (PC) quality measures. Methods: Drawing on data from the Center for Maternal and Infant Outcomes Research in Translation (COMFORT) study—a multi-site national cohort of pregnant Veterans—three analyses were conducted: (1) a retrospective cohort analysis assessing racial and ethnic differences in unplanned cesarean birth among 314 primiparous Veterans with term, singleton deliveries; (2) a mixed-methods pilot study evaluating the feasibility and acceptability of doula care among 39 referred Veterans; and (3) a focused analysis of 27 BIPOC Veterans describing their provider selection and prioritization of three PC quality measures. Results: Non-Hispanic BIPOC Veterans had significantly higher risk of unplanned cesarean birth than White Veterans, even after adjusting for clinical risk. Doula care seemed feasible and acceptable as a potential VA maternity care benefit, with participants expressing strong interest in future use. Most Veterans selected providers based on geographic proximity or CCN inclusion. Although participants were largely unaware of obstetric quality measures or how to access and interpret such data prior to the study, when asked to rate three PC quality measures, they consistently prioritized infant safety—rating “unexpected complications in term newborns” as most important. Conclusion: This dissertation identifies disparities and structural barriers in VA-purchased maternity care and underscores the need for improved oversight of the CCN, culturally responsive support models, and Veteran-centered tools for informed perinatal decision-making.Publication Sarcoidosis Presenting as a Giant Pulmonary Bulla With Concurrent COVID-19 Infection(2025-05-08)Sarcoidosis is a systemic granulomatous disease that predominantly affects the lungs. However, its presentation as a giant pulmonary bulla is exceptionally rare. Its association with COVID-19 has raised new concerns regarding disease exacerbation and misdiagnosis. We report a case of a 38-year-old man who developed a large left lower lobe bulla in the context of recent COVID-19 infection. Initial misinterpretation of the bulla as loculated pneumothorax nearly led to an unnecessary chest tube placement. A subsequent thoracotomy with lobectomy revealed nonnecrotizing granulomas, confirming sarcoidosis. The patient showed spontaneous remission without requiring treatment. This case highlights the importance of multidisciplinary discussions in atypical lung presentations to prevent mismanagement.Publication Assessment of Family Involvement as A Determinant of Rehabilitative Therapy Administration, Change in Depression Severity, and Risk of Pressure Injuries Development in U.S. Nursing Home Residents(UMass Chan Medical School, 2025-05-06)ABSTRACT Background: As older adults transition to nursing homes from the community, their health and quality of life in nursing homes are significantly influenced by various factors, including family involvement in care planning. Family involvement is associated with better health outcomes in older adults, yet its impact on specific conditions like therapy administration, depression, and pressure injuries among nursing home residents remains understudied. This dissertation addresses these gaps by examining the role of family involvement in these key areas. Methods: Using national data from the Minimum Data Set (MDS) 3.0, this dissertation explores the influence of family involvement on nursing home care and health outcomes from 2014 to 2019. The study includes three aims: 1) assessing the association between family involvement and rehabilitative therapy administration among newly admitted residents transferred from acute care in 2019; 2) examining the relationship between perceived family involvement and changes in depression severity in long-stay residents from 2014 to 2019, and 3) evaluating the impact of family involvement on the risk of developing stage 2 or higher pressure injuries in long-term care residents from 2014 to 2019. Statistical methods included linear regression, Poisson regression, and generalized estimating equations (GEEs). Results: The first study included 2,112,330 residents aged 50 years and older. In Aim 1, residents who reported family involvement as "Very Important" received an average of 247 minutes of individual physical therapy and 236 minutes of individual occupational therapy, compared to 222 minutes of individual physical therapy and 215 minutes of individual occupational therapy among those who found it "Important, but no choice." Adjusted analyses showed that residents who rated family involvement as "Not Important at All" received 21 fewer therapy minutes (95% CI: -27, -15) compared to those who valued it as "Very Important." In Aim 2, among 2,043,308 long-stay nursing home residents, those with none-to-low baseline depression who perceived family involvement as "Not Important at All" had a 10% higher risk of significant worsening of depression symptoms (RR: 1.10, 95% CI: 1.06, 1.14) after adjusting for confounders, compared to those who considered it "Very Important." Conversely, among residents with moderate to moderately severe baseline depression, those who perceived family involvement as "Not Important at All" had a 33% higher risk of significant worsening (RR: 1.33, 95% CI: 1.10, 1.61) compared to the "Very Important" group, after adjusting for covariates. In Aim 3, among 579,958 residents, the relative risk of developing stage 2 or higher-pressure injuries was 0.97 (95% CI: 0.78, 1.22) for those who rated family involvement as "Not Important at All," compared to those who viewed it as "Very Important." Subgroup analysis revealed a higher risk for residents with severe physical impairments (RR: 1.34, 95% CI: 0.94, 1.93) and those with no urine output/ostomy (RR: 1.59, 95% CI: 0.88, 2.86). Conclusions: This dissertation underscores the significant role of family involvement in enhancing the care and health outcomes of nursing home residents. Higher family engagement is associated with increased rehabilitative therapy use, reduced risk of worsening depression, and nuanced effects on pressure injury development, particularly among vulnerable subgroups. These findings highlight the need for nursing homes to foster family involvement in care planning as a strategy to improve residents' overall health and well-being. Implementing policies that encourage family engagement could lead to more personalized and effective care, ultimately enhancing the quality of life for older adults in nursing homes.Publication Computationally designed proteins mimic antibody immune evasion in viral evolution(2025-05-06)Recurrent waves of viral infection necessitate vaccines and therapeutics that remain effective against emerging viruses. Our ability to evaluate interventions is currently limited to assessments against past or circulating variants, which likely differ in their immune escape potential compared with future variants. To address this, we developed EVE-Vax, a computational method for designing antigens that foreshadow immune escape observed in future viral variants. We designed 83 SARS-CoV-2 spike proteins that transduced ACE2-positive cells and displayed neutralization resistance comparable to variants that emerged up to 12 months later in the COVID-19 pandemic. Designed spikes foretold antibody escape from B.1-BA.4/5 bivalent booster sera seen in later variants. The designed constructs also highlighted the increased neutralization breadth elicited by nanoparticle-based, compared with mRNA-based, boosters in non-human primates. Our approach offers targeted panels of synthetic proteins that map the immune landscape for early vaccine and therapeutic evaluation against future viral strains.