DR64 DataRelease
Release Date: May 2026
New Studies: 11
Updated Studies: 2
New Studies
| SDY3242: A causal link between autoantibodies and neurological symptoms in long COVID | ||||||||||
| Status: | New | |||||||||
| Description: | Acute SARS-CoV-2 infection triggers the de novo production of diverse and functional autoantibodies (AABs), even after mild illness. Previous studies have shown that autoantibodies remain persistently elevated in a subset of individuals with long COVID (LC). However, it is still unclear whether these autoantibodies cause symptoms in LC. Using a human protein array with over 21,000 proteins and an antibody pull-down of autoantigens followed by mass spectrometry, we identified a broad range of AAB targets among individuals with LC that correlated with their symptom profiles. We found increased AABs against proteins in the central and peripheral nervous systems, as well as peripheral tissues, in individuals with LC displaying neurocognitive and neurological symptoms. Purified Immunoglobulin G (IgG) samples from these individuals reacted with tissue sections of human locus coeruleus, thalamus, adrenal gland, thyroid, and showed cross-reactivity with mouse sciatic nerve and meninges. Autoantibody levels reactive to CNS antigens were linked to symptoms such as headaches and loss of taste and smell. Passive transfer of IgG from patients to naïve mice caused increased fatigue-like behavior and thermal hyperalgesia, aligning with patients’ reports of chronic pain. Similarly, loss of balance and coordination in the rotarod test in mice injected with IgG matched with patient-reported dizziness. Moreover, transfer of purified IgG from patients with chronic pain caused damage to small peripheral nerve fibers and increased neuronal activity in pain-related brain regions in mice. Our findings demonstrate that transferring IgG from LC patients into mice can reproduce certain neurological symptoms, suggesting that targeting AABs might offer therapeutic benefits for this subgroup of LC. | |||||||||
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| DOI: | 10.21430/M3K5VDQRSM | |||||||||
| Subjects: | 0 | |||||||||
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| SDY3386: Swaney Human milk Olink | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Comparison of human milk protein levels from mothers with differing farming exposures | ||||||||||||
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| DOI: | None | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Assays: | None | ||||||||||||
| Clinical Assessments: | None | ||||||||||||
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| SDY3390: Understanding T cells reactive towards tumor associated antigens (TAA) and autoantigens in cancer and down syndrome human subjects | ||||||||||
| Status: | New | |||||||||
| Description: | Goal of the study was to identify T cell biomarkers that predict autoimmune-related adverse events associated with immune checkpoint inhibition (ICI) therapy. The central hypothesis being that the frequency and phenotype of T cells specific for self-antigens predicts autoimmune related adverse events, which in turn predicts therapeutic efficacy in some patients. Conversely, people with down syndrome show significantly decreased risk of solid tumors spanning almost all major types and are highly predisposed to autoimmunity. Thus the intersection of those with cancer and those with down syndrome creates an overlap in the immune dysregulation that provide a unique window to understand the role T cells play in cancer and autoimmunity. We determine how PD-1 ICI therapy alters the frequency and phenotypes of tumor and auto-antigen specific T cells in a longitudinal cohort of PD-1 ICI treated subjects and these T cells in a non-cancer setting within a cohort of down syndrome subjects. For this study, we utilize an activation induced marker assay (AIM) where T cells specific towards tumor associated antigens and thyroid autoantigens are characterized using spectral cytometry. | |||||||||
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| DOI: | 10.21430/M39T6INE4T | |||||||||
| Subjects: | 0 | |||||||||
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| Publications: | None | |||||||||
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
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| SDY3391: Identifying T cell biomarkers that predict autoimmune-related adverse events | |||||||
| Status: | New | ||||||
| Description: | Goal of the study was to identify T cell biomarkers that predict autoimmune-related adverse events associated with immune checkpoint inhibition (ICI) therapy. The central hypothesis being that the frequency and phenotype of T cells specific for self-antigens predicts autoimmune related adverse events, which in turn predicts therapeutic efficacy in some patients. Conversely, people with down syndrome show significantly decreased risk of solid tumors spanning almost all major types and are highly predisposed to autoimmunity. Thus the intersection of those with cancer and those with down syndrome creates an overlap in the immune dysregulation that provide a unique window to understand the role T cells play in cancer and autoimmunity. We determine whether PD-1 ICI therapy alters the CD4 and CD8 T cell landscape in cancer patients making it similar to that seen in individuals with natural autoimmunity. In particular, determine if T cell profiles found in autoimmunity can be identified within the T cell compartment of ICI-treated individuals using mass cytometry. | ||||||
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| DOI: | 10.21430/M3QXBC5KVI | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
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| SDY3411: Impact of lung transplant on lung remodeling | |||||||
| Status: | New | ||||||
| Description: | Respiratory viral infections remain an important risk factor for long-term lung transplantation survivors. Successful transplants and development of pulmonary tolerance relies on the formation of bronchus-associated lymphoid tissue (BALT) structures, enriched in Foxp3+ regulatory T cells. However, the impact of a pre-established regulatory immune environment in the outcome of a subsequent pulmonary viral infection is unknown. Using a murine model of the seasonally circulating parainfluenza viruses, we found that acute infection of tolerogenic lungs results in a reduction of central-memory T cells in the lung with BALT remaining in the pulmonary grafts long-term. During long-term virus infection we found that pathological chronic type-2 inflammatory response characteristic of severe parainfluenza virus infection was reduced in transplanted lungs, with significant increase of Areg+ cells in comparison with native lungs. More strikingly, virus-infected transplanted lungs displayed significant reduction of Krt5+ and Krt8+ lesions in comparison with infected native lungs, indicating a reduction of dysplastic alveolar regeneration areas. Post-viral chronic lung inflammation and tissue remodeling events progressed similarly in both lungs in a syngeneic lung transplant model, confirming the need for a tolerogenic response for protection. Our findings not only suggests that the immune microenvironment induced in tolerant lung grafts can deeply alter the progression of a respiratory viral infection, but also expands the understanding of the long-term events following lung transplantation (Only experiments performed in the Lopez Lab are deposited here) | ||||||
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| DOI: | 10.21430/M3Q812WWD9 | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
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| SDY3428: Impact of cbVGs in the host transcriptome at a single cell level | |||||||
| Status: | New | ||||||
| Description: | The antiviral response to several clinically significant viruses, including respiratory syncytial virus and parainfluenza virus, is driven by copy-back viral genomes (cbVGs) generated during virus replication. However, the broader impact of cbVGs on the functional states of host cells remains undefined. Here, we developed a single-cell RNA-sequencing and computational framework to map cbVG-driven host responses during Sendai virus infection. Unsupervised profiling identified distinct transcriptional states throughout the course of infection, highlighting a shift from early antiviral signaling to later inflammatory and remodeling programs. Stratifying infected cells by cbVG status demonstrated that cbVG-positive cells initiate interferon and chemokine programs, which later spread to cbVG-negative cells. At later stages, cbVG-positive cells acquire additional signaling, cytoskeletal, transcriptional, and stress-adaptation programs, which are absent in cbVG-clean infection. This work defines the broader cbVG-driven layered and dynamic host response and provides a valuable high-resolution resource of the temporal cellular response to a virus infection. | ||||||
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| DOI: | 10.21430/M3ZS5JA7LW | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
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| SDY3485: LNP vs LION multivalent in NHPs | |||||||
| Status: | New | ||||||
| Description: | This study was conducted to investigate how vaccine formulation influences systemic innate immune responses and antigen-specific antibody responses following administration of multi-component replicon RNA (repRNA) vaccines. RepRNA vaccines are a promising platform for infectious disease prevention due to their ability to elicit strong immune responses at relatively low doses. However, prior studies have demonstrated that formulation with lipid nanoparticles (LNPs) can induce substantial systemic inflammatory responses, which may negatively impact vaccine safety and immunogenicity. This study addresses a critical knowledge gap regarding how formulation-dependent innate immune activation affects downstream adaptive immune responses, particularly in the context of multi-antigen vaccine strategies. The primary objective of this study was to compare the immunogenicity and systemic innate immune responses elicited by a multi-component repRNA vaccine formulated either with conventional lipid nanoparticles (LNP) or with a cationic nanocarrier (LION). A secondary objective was to determine the relationship between early systemic cytokine responses—especially type I interferons—and the magnitude of antigen-specific binding and neutralizing antibody responses. The central hypothesis was that excessive systemic innate immune activation, particularly interferon responses, may impair antigen expression and subsequent antibody generation for certain vaccine components. The study utilized a controlled experimental design in a non-human primate (NHP) model. Six pigtail macaques were divided into two groups (n=3 per group) and immunized intramuscularly with a multi-component repRNA vaccine. The vaccine encoded virus-like particle (VLP) antigens from three enterovirus D68 (EV-D68) subclades (A1, B1, and C), as well as glycoprotein antigens (F and G) from respiratory syncytial virus (RSV). Each antigen component was delivered at 20 μg, for a total dose of 100 μg per immunization. Animals received two doses administered eight weeks apart, and longitudinal blood samples were collected at multiple timepoints to assess immune responses. Biological samples, including serum and peripheral blood mononuclear cells (PBMCs), were collected for immunological and transcriptomic analyses. Systemic cytokine responses were measured using ELISA and multiplex bead-based assays, with a focus on interferon-alpha (IFN-α) and other inflammatory cytokines. Gene expression profiling of PBMCs was performed using NanoString technology to evaluate activation of innate and adaptive immune pathways. Antigen-specific antibody responses were assessed by ELISA for binding antibodies and by neutralization assays for EV-D68-specific functional antibodies. The dataset generated includes longitudinal serum cytokine measurements, PBMC transcriptomic profiles, antigen-specific binding antibody titers, and neutralizing antibody responses across multiple viral antigens. Data preprocessing included standard quality control, normalization of gene expression data, and statistical analyses including differential expression and correlation analyses between cytokine levels and antibody responses. Key findings from this study demonstrate that vaccine formulation significantly influences both systemic innate immune activation and antigen-specific immunogenicity. RepRNA formulated with LNP induced strong systemic interferon and inflammatory cytokine responses, whereas LION-formulated repRNA elicited more localized innate immune activation with reduced systemic cytokine levels. Notably, elevated early systemic IFN-α responses were inversely correlated with neutralizing antibody responses to EV-D68, suggesting that excessive systemic innate activation may impair immunogenicity for certain antigens. In contrast, LION formulation enabled robust antibody responses across all antigen components, including EV-D68. Overall, this study provides important insights into the interplay between vaccine formulation, innate immune activation, and adaptive immune outcomes. The findings highlight the importance of controlling systemic inflammatory responses to optimize the efficacy and safety of multi-component RNA vaccines. The dataset serves as a valuable resource for understanding formulation-dependent immune mechanisms and may support future efforts in vaccine design, biomarker discovery, and comparative immunological analyses across platforms. | ||||||
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| DOI: | 10.21430/M32E3X1J9N | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
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| SDY3506: Polyfunctional T Helper Cells in Checkpoint-Induced Diabetes | |||||||
| Status: | New | ||||||
| Description: | Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, but their use is limited by the development of autoimmunity in healthy tissues as a side effect of treatment. Such immune-related adverse events (IrAE) contribute to hospitalizations, cancer treatment interruption, and even premature death. ICI-induced autoimmune diabetes mellitus (ICI-T1DM) is a life-threatening IrAE that presents with rapid pancreatic ?-islet cell destruction leading to hyperglycemia and life-long insulin dependence. JAKi therapy impaired Tfh cell differentiation in PBMC from patients with ICI-T1DM. These studies highlight CD4+ Tfh cells as underrecognized but critical mediators of ICI-T1DM that may be targeted with JAKi to prevent this grave IrAE. | ||||||
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| DOI: | 10.21430/M35W7Q4EFR | ||||||
| Subjects: | 17 | ||||||
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| Clinical Assessments: | None | ||||||
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| SDY3510: Chen_et_al_JCI_2025 | |||||||
| Status: | New | ||||||
| Description: | Type 1 diabetes mellitus (T1D) is a chronic disease caused by an unremitting autoimmune attack on pancreatic β cells. This autoimmune chronicity is mediated by stem-like progenitor CD8+ T cells that continually repopulate the pool of β cell–specific cytolytic effectors. Factors governing the conversion of progenitors to effectors, however, remain unclear. T1D has been linked to a chromosomal region (Xp13-p11) that contains the epigenetic regulator UTX, which suggests a key role for UTX in T1D pathogenesis. Here, we show that T cell–specific UTX deletion in NOD mice protects against T1D development. In T cells of NOD mice and patients with T1D, UTX ablation resulted in the accumulation of CD8+ progenitor cells with a concomitant decrease of effector cells, suggesting a key role for UTX in poising progenitors for transition to effectors. Mechanistically, UTX’s role in T1D was independent of its inherent histone demethylase activity but instead relied on binding with transcription factors (TCF1 and STAT3) to coregulate genes important in the maintenance and differentiation of progenitor CD8+ T cells. Together, these findings identify a critical role for UTX in T1D and the UTX:TCF1:STAT3 complex as a therapeutic target for terminating the long-lived autoimmune response. | ||||||
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| DOI: | 10.21430/M3AZSYFEZG | ||||||
| Subjects: | 14 | ||||||
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| Clinical Assessments: | None | ||||||
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| SDY3641: Engineered T cells for improved migration into solid tumor sites | ||||||||||
| Status: | New | |||||||||
| Description: | Adoptive transfer T cell-based immunotherapies and checkpoint inhibitor immunotherapy have shown significant promise in the treatment of cancers. However, checkpoint inhibitor therapy still fails in a majority of patients and chimeric antigen receptor (CAR)-T cells are ineffective against most solid tumors. In large part, these failures are due to the fact that frequently tumors are mostly devoid of T cells or that T cells are present only in the tumor-surrounding stroma but largely excluded from the tumor mass. Tumors are often surrounded by extensive collagen-rich extracellular matrix (ECM) structures, which impede the entry of T cells into the tumor mass. T cell paucity or exclusion from the tumor site correlate with poor prognosis, limited efficacy of checkpoint inhibitor immunotherapies, and ineffectiveness of CAR-T cell therapy against solid tumors. Most cellular tumor immunotherapy approaches to date have focused on reversing T cell exhaustion and increasing persistence of tumor-specific T cells and CAR-T cells. However, these approaches generally do not solve the issue of recruitment and infiltration of therapeutic T cells into the tumor. The overall goal of this proposal is to engineer T cells to enhance their migration into tumors to increase their anti-tumor activity in ‘cold’ tumors and tumors that exclude T cells from the tumor mass. Our exploratory R21 proposal specifically addresses the unmet need to improve migration of T cells into tumors by creating T cells with increased capacity to migrate through restrictive environments. We have found that Formin-like-1 (FMNL1) promotes efficient T cell extravasation, motility through confined environments, and interstitial migration in vivo. Furthermore, our preliminary data using a melanoma model show that overexpression of FMNL1 significantly increases the number of tumor-specific T cells present at the tumor site. Thus, we hypothesize that T cells engineered to overexpress FMNL1, or its active mutants, will have increased trafficking to the tumor site, deeper infiltration into the tumor mass, and enhanced anti-tumor activity. We will test our hypothesis with the following Aims: Aim 1. Determine if overexpression of FMNL1 or its active mutants enhances tumor-specific T cell migration and accumulation within tumors. Aim 2. Determine if T cells engineered to overexpress FMNL1 have increased anti-tumor activity and improve the efficacy of checkpoint inhibitor therapy. Overall, we will establish and validate a platform for T cell bioengineering to improve T cell migration into tumor sites that can be applied to tumor-infiltrating lymphocyte (TIL) transfer therapy and CAR-T cell therapy for solid tumors. Our novel approach can both improve the ability of T cells to extravasate at the tumor site, and enhance the capacity of T cells to migrate through restrictive tissue barriers to infiltrate the tumor mass. From a future translational standpoint, an additional advantage of this system is that the T cell infiltration enhancement provided by FMNL1 is not limited to a particular tumor antigen and is not MHC restricted. Overall, our work has the potential to significantly improve the treatment of solid tumors using adoptive T cell transfer therapies. | |||||||||
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| DOI: | 10.21430/M34PX11DIU | |||||||||
| Subjects: | 11 | |||||||||
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| SDY3646: Seasonal vaccine-induced immunity shows preserved cross-reactivity to H3N2 subclade K in adults | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | Not Provided | |||||||||||||||
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| DOI: | 10.21430/M3A8H76DYN | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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Updated Studies
| SDY3453: Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derive | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | This cross-sectional study examined the transcriptional and functional impact of maternal SARS-CoV-2 infection on fetal Hofbauer cells (HBCs) and their potential utility as surrogates for fetal microglial programming. We enrolled 24 pregnant individuals delivering at Massachusetts General Hospital between March 2021 and June 2023: 10 with confirmed SARS-CoV-2 infection during pregnancy (median 12.2 weeks prior to delivery, unvaccinated) and 14 matched controls with no infection history. HBCs were isolated from term placentas using Percoll gradient separation and negative immunoselection (anti-EGFR, anti-CD10), yielding 31,719 high-quality cells for 10x Genomics single-cell RNA sequencing. We identified 8 fetal HBC subclusters (distinguished from maternal PAMMs using sex-chromosome markers DDX3Y/XIST in male placentas, N=10) with distinct baseline transcriptional programs including pro-inflammatory (HBC 3,4,7), stress response (HBC 0,1), tissue repair (HBC 2), and protein processing (HBC 6) phenotypes. Differential gene expression analysis revealed cluster-specific SARS-CoV-2 effects, with HBC 1 (723 DEGs) and HBC 5 (566 DEGs) most affected by number of DEGs, showing altered phagocytosis pathways and enrichment of neuroinflammation-associated signatures. Using direct cytokine reprogramming (IL-34, GM-CSF), we transdifferentiated HBCs into microglia-like cells (HBC-iMGs) expressing IBA1, TMEM119, P2RY12, PU.1, and CX3CR1. Functional phagocytosis assays using pHrodo Red-labeled synaptosomes from iPSC-derived neurons demonstrated significantly reduced phagocytic index in SARS-CoV-2-exposed HBC-iMGs (N=10) versus controls (N=9), with preserved cellular morphology (solidity, eccentricity). These findings establish proof-of-concept for using patient-specific HBC-iMGs as personalized models of fetal microglial programming following maternal immune activation. |
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| DOI: | 10.21430/M3KQHPU8ND | ||||||||||||
| Subjects: | 24 | ||||||||||||
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| SDY3461: Increasing scalability of single-cell sample processing using Seq-Well S3 | |||||||||
| Status: | Updated | ||||||||
| Description: | In-depth analyses of clinical samples have the potential to provide unparalleled insights into the cellular mechanisms that underlie both health and disease, as well as therapeutic and prophylactic responses. However, these specimens are often paucicellular, necessitating the use of workflows that maximize the amount of information that can be learned. Here, we provide a detailed protocol for generating and analyzing single-cell multi-omic data from low-input samples with the Seq-Well S3 platform. We further describe a matched pipeline for sample hashing that reduces costs and sources of technical variation in the resulting data while also enhancing throughput. In brief, our streamlined and efficient methodology involves: (1) optionally staining single-cell suspensions with antibody-oligonucleotide conjugates for cell surface protein quantification and/or sample multiplexing; (2) generating Seq-Well S3 sequencing libraries; (3) optionally producing bulk-RNA sequencing libraries via SMART-seq2 to support genetic demultiplexing; and, (4) computationally analyzing the resulting data. Each step herein has been designed to leverage readily available reagents and standard laboratory equipment, significantly lowering barriers to entry for researchers. The overall protocol can yield high-quality multi-omic insights from samples in under a week. | ||||||||
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| DOI: | 10.21430/M35I93AMFS | ||||||||
| Subjects: | 4 | ||||||||
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