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 Restricted Cooperativity and communication between the active sites of the dimeric SARS-CoV-2 main protease(2026-01-16)The coronaviral main protease (M) has been the subject of various biochemical and structural studies and a drug target against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. SARS-CoV-2 M is active as a dimer, but despite apparent cooperativity in catalytic activity, how the two distal active sites communicate and modulate binding and/or catalysis is unclear. Here, we have investigated the interplay between cooperativity, dimerization, and substrate cleavage in SARS-CoV-2 M through a combination of enzymatic assays, crystal structures, and protein characterization. To disentangle the contribution of each active site to the observed enzymatic activity, we developed a cleavage assay involving heterodimers of active and inactive (catalytic residue mutated or inhibitor-bound) monomers. Notably, we found that heterodimerization increased cleavage efficiency per active monomer. In addition, we mapped a network of critical residues bridging the two active sites and probed this network through engineered mutations. By dissecting the cooperativity and communication between the active sites, we provide insights into the M reaction cycle and functional significance of its dimeric architecture.Publication Open Access Adulting Shorts: Money Moves — Zero-Based Budgeting Made Easy(UMass Chan Medical School, 2026-01-16)Zero-based budgeting is a financial planning method where you allocate every dollar of your income to specific categories—such as expenses, savings, or debt repayment—so that your total income minus your total expenses equals zero at the end of each budgeting period (often monthly). This approach helps you plan intentionally, knowing exactly where your money goes, and makes it easier to adjust priorities as your needs change. This comic by the Learning & Working RRTC provides a visually engaging, concise guide to zero-based budgeting. Designed to support young adults and those transitioning to independence, the comic breaks down the steps of zero-based budgeting in an accessible and relatable way, helping readers gain confidence and control over their finances.Publication Metadata only Cultural-Social-Economic Background and Community Engagement Impacting COVID-19 Vaccination Uptake Among Pregnant and Lactating Refugee Women(2026-01-16)COVID-19 vaccine uptake in pregnant and lactating refugee women remains understudied despite their high risk of severe health outcomes. Our survey of 672 refugee women who gave birth at an urban hospital in a southwestern U.S. state between 2020 and 2023 revealed a concerningly low vaccination rate, with only 45.4% receiving one or more COVID-19 vaccine doses. Vaccination status was highly heterogeneous, with uptake ranging from 76.9% among women relocated from Afghanistan and South Asia to merely 23.8% among those from Congo, Tanzania, and several other African nations. Women residing in low-income areas and socioeconomically segregated communities were less likely to be vaccinated. Importantly, engagement with cultural health navigators (CHNs)-certified, multilingual, and bicultural individuals who share lived experiences of forced displacement with refugees and facilitate their healthcare navigation, education, and trust-building-helped mitigate these disparities. CHN support increased vaccination uptake among initially reluctant individuals, with some initiating vaccination during pregnancy. The effectiveness of CHN support varied by country of origin, underscoring the need for culturally tailored interventions to promote health equity in underserved populations.Publication Metadata only A new framework for pulmonary nodules: how terminology impacts management(2026-01-16)The Fleischner Society recently updated its Glossary of Terms of Thoracic Imaging, proposing a new approach in the assessment of pulmonary nodules. These updates include changes in terminology regarding the definition of nodule size, as well as inclusive terminology to provide a more flexible framework in the assessment of pulmonary nodule morphology. The broad categories "simple" and "complex" are introduced for more versatile characterization to encompass the wide nodule structure and morphology we see in clinical practice, beyond the classic trichotomy of solid, subsolid, and part-solid. Another key aspect in the assessment of pulmonary nodules includes longitudinal evaluation, a small part of which is growth, namely changes in nodule size. While there is a strong focus on changes in size, other features, such as changes in components, also play a key role in nodule assessment. These include transition in morphology and structure: from simple to complex, and complex to simple; in regard not only to the core of the nodule, but also to borders and contours. This paper examines how the updated terminology aligns with and impacts management within the current nodule management paradigms. KEY POINTS: Question The updated Fleischner Society Glossary of Terms introduces a new definition for nodule size and terminology regarding nodule morphology, and these features are tied to management. Findings Nodule size and morphology are important factors in characterizing and assessing the malignant potential of pulmonary nodules. Clinical relevance The increased threshold for nodule size aims to decrease the workup of small, likely benign nodules. New terminology on morphology allows more flexible characterization to address the broad range seen in clinical practice and offers an opportunity for incorporation in nodule management systems.Publication Open Access HSD17B13 Couples Hepatocellular Lipid Dysregulation to Stellate Cell Activation through a TGFβ-1–Dependent Mechanism(UMass Chan Medical School, 2026-01-15)Metabolic dysfunction–associated steatohepatitis (MASH) is a progressive liver disease characterized by hepatocellular lipid overload, inflammatory activation, and hepatic stellate cell (HSC)–mediated fibrogenesis. Human genetic studies have identified loss-of-function (LoF) variants in 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) that confer robust protection against advanced fibrosis and cirrhosis, establishing HSD17B13 as a critical modifier of MASH severity. However, the mechanisms linking HSD17B13 activity to fibrogenesis remain incompletely understood. Here, we demonstrate that both native and catalytically deficient HSD17B13 (mHSD) localize to lipid droplets (LDs) in human hepatocytes. Only catalytically active HSD17B13 enhances lipid storage and markedly upregulates the lipogenic transcriptional regulator carbohydrate-responsive element–binding protein (ChREBP). This HSD17B13–driven lipogenic program promotes activation of human LX2 stellate cells both in direct co-culture and upon exposure to hepatocyte-conditioned medium (CM). Screening of candidate signaling mediators revealed that transforming growth factor β-1 (TGFβ-1) is uniquely and robustly induced by HSD17B13 expression, whereas mHSD elicits minimal induction. Notably, siRNA-mediated TGFB1 knockdown or antibody neutralization of active TGFβ-1 effectively abrogates CM-induced LX2 activation and collagen synthesis. Collectively, these findings delineate an HSD17B13–TGFβ-1 signaling pathway that mechanistically couples hepatocellular lipid dysregulation to stellate cell-mediated fibrogenesis. This work reveals a dual metabolic and profibrotic role for HSD17B13 and underscores its therapeutic potential as a target for mitigating the transition from simple steatosis to steatohepatitis.