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 Impact of preanalytical factors on liquid biopsy in the canine cancer model(2026-06-11)BACKGROUND: While liquid biopsy has potential to transform cancer diagnostics through minimally-invasive detection and monitoring of tumors, the impact of preanalytical factors such as the timing and anatomical location of blood draw is not well understood. METHODS: To address this gap, we leveraged pet dogs with spontaneous cancer as a model system for liquid biopsy of plasma cell-free DNA (cfDNA), as their compressed disease timeline facilitates rapid diagnostic benchmarking. We examined key cfDNA metrics, including DNA concentration in plasma, as well as tumor fraction and fragment size ratio derived from ultra low pass whole genome sequencing. RESULTS: We show that liquid biopsy metrics in dogs are consistent with reported human metrics. The tumor content of samples is slightly higher when blood is obtained from a central vein closer to the tumor. Metrics also differ between lymphoma and non-hematopoietic cancers, supporting cancer-type-specific interpretation. Disease status tracks with liquid biopsy findings over the course of treatment over both short (hours to days) and long (weeks to months) time frames, and trends of increased tumor fraction and other metrics are observed prior to clinical relapse in dogs with lymphoma and osteosarcoma. CONCLUSIONS: Together, these data support the utility of pet dogs with cancer as a relevant system for advancing liquid biopsy platforms. Liquid biopsy allows the use of body fluids such as blood to diagnose and monitor patients with cancer. Dogs develop several cancers that are similar to those in humans, but their faster disease progression enables rapid data collection. We used data from pet dogs with cancer to ask whether blood draw techniques and patient characteristics impact the reliability of liquid biopsy. As in humans, findings from liquid biopsy in dogs match results of conventional biopsy. Also, blood drawn from the vein in a dog’s neck (jugular vein) contains more DNA from tumors than blood drawn from leg veins. In dogs that had lymphoma or osteosarcoma, liquid biopsy detects changes in cancer burden over time that match clinical disease. Our findings show that the information from liquid biopsy in dogs with cancer mirrors that found in human patients, making them a good model system to help improve approaches across both species.Publication Open Access Nodular Fasciitis of the Piriformis Muscle Initially Concerning for Metastasis in a Patient With Previous History of Colon Adenocarcinoma: A Case Report(2026-06-10)CASE: We report a case of nodular fasciitis (NF) of the hip in a patient with a history of colon adenocarcinoma, concerning for metastasis. PET/CT showed a hypermetabolic lesion, and MRI revealed a well-defined, enhancing intramuscular mass. Histology identified fascicles of spindle or stellate cells with ovoid nuclei in myxoid and collagenous stroma with sparse inflammatory cells. On immunohistochemistry, the spindle cells expressed smooth muscle actin. Fluorescence in situ hybridization (FISH) demonstrated ubiquitin-specific protease 6 (USP-6) gene rearrangement, confirming the diagnosis. CONCLUSION: NF is a benign, rapidly growing soft tissue lesion mimicking malignancy. Surgical excision is curative. Accurate diagnosis can prevent unnecessary interventions.Publication Open Access Transcriptional responses to chronic oxidative stress require cholinergic activation of G-protein-coupled receptor signaling(2026-06-08)Organisms have evolved protective strategies that are geared toward limiting cellular damage and enhancing organismal survival in the face of environmental stresses, but how these protective mechanisms are coordinated remains unclear. Here, we define a requirement for neural activity in mobilizing the antioxidant defenses of the nematode both during chronic oxidative stress and prior to its onset. We show that acetylcholine-deficient mutants are particularly vulnerable to chronic oxidative stress. We find that extended oxidative stress mobilizes a broad transcriptional response which is strongly dependent on both cholinergic signaling and activation of the muscarinic G-protein acetylcholine-coupled receptor (mAChR) GAR-3. Gene enrichment analysis revealed a lack of upregulation of proteasomal proteolysis machinery in both cholinergic-deficient and mAChR mutants, suggesting that muscarinic activation is critical for stress-responsive upregulation of protein degradation pathways. Further, we find that GAR-3 overexpression in cholinergic motor neurons prolongs survival during chronic oxidative stress. Our studies demonstrate neuronal modulation of antioxidant defenses through cholinergic activation of G protein-coupled receptor signaling pathways, defining new potential links between cholinergic signaling, oxidative damage, and neurodegenerative disease.Publication Open Access MORC3 represses a tandem repeat enhancer to regulate interferon(2026-06-05)The antiviral protein MORC3 is frequently inhibited by viruses. To counteract viral antagonism, MORC3 represses a noncanonical pathway of type-I-interferon (IFN) such that viral inhibition of MORC3 triggers ( > 10,000-fold) IFN induction. How MORC3 represses this pathway, and why IFN induction upon MORC3 loss is so potent without canonical IRF3/7 transcription factors, is unknown. Here, we show that MORC3 restricts chromatin accessibility at tandem repeat elements harboring up to 61 homotypic transcription factor motifs. One such element becomes a potent enhancer of IFNB1 upon MORC3 loss. Its motif cluster contains 45 PU.1 binding sites and is necessary and sufficient for MORC3-mediated repression and enhancer activity upon MORC3 loss. PU.1 recruits MORC3 to repress this enhancer by recruiting DAXX and enabling H3.3 incorporation. Upon MORC3 loss, PU.1 drives IRF3/7-independent IFN induction. Other restricted tandem repeats contain homotypic motif clusters of SPI, AP-1, and SP/KLF transcription factors. Our findings uncover a TF motif cluster-driven repression mechanism by MORC3 at tandem repeats, enabling specific repression of an IFNB1 enhancer such that viral antagonism of MORC3 induces interferon.Publication Open Access An interpretable machine learning framework for dog breed inference and ancestry decomposition [preprint](2026-06-04)The over 300 currently recognized breeds of domesticated dogs are the culmination of centuries of intense artificial selection and recurrent population bottlenecks. While breed labels are widely used in genetic and veterinary studies, inferring breed identity from genomic data remains challenging due to the high dimensionality of genotype data, uneven sampling across breeds, and admixture resulting in mixed-breed individuals. Here, we present an interpretable machine learning framework to infer dog breed labels from genome-wide SNP data. Our approach combines dimensionality reduction with a multi-output random forest model that maps genetic variation to a continuous representation of breed membership, enabling both classification and mixed-breed inference. We apply this framework to the Dog Aging Project (DAP) dataset of 6,572 purebred and mixed-breed dogs across 100 breed classes, achieving 91.7% accuracy with an overlap-based metric, outperforming an ADMIXTURE-based benchmark that achieved 87.8% accuracy. Notably, we find that as few as 150 informative SNPs are sufficient to achieve near-maximal predictive performance, highlighting the highly structured nature of canine genetic variation. We also introduce a SNP importance score metric that links model predictions back to individual genetic variants. Analysis of top-ranked variants reveals loci previously associated with morphological, pigmentation, and behavioral traits, as well as candidate loci lacking prior phenotypic annotation, supporting both the biological relevance and discovery potential of the framework. Together, these results demonstrate that our framework provides an accurate, flexible, and interpretable approach to predict breed ancestry, with applications in veterinary genomics, canine population genetics, and the identification of loci underlying hallmark breed phenotypes.