Elizabeth R. Duffy's research while affiliated with University of Massachusetts Boston and other places
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Publications (67)
Background
Longitudinal serology studies can assist in analyzing kinetics of antibodies to the SARS-CoV-2 virus, helping to inform public health decision-making. Our study aims to characterize circulating antibody trends over 18 months in vaccinated participants with and without evidence of COVID-19 infection.
Methods
A cohort of healthcare worker...
Background:
Boston Medical Center (BMC) is a safety net hospital in Boston, and from the initial wave of COVID-19 there has been an overwhelming concern about the exposure of healthcare workers (HCWs) to SARS-CoV-2.
Methods:
We conceived a study to follow a cohort of BMC HCWs, beginning in July 2020 and continuing for 15 months, collecting surve...
Over 15-months we found that anti-spike RBD SARS-CoV-2 antibody concentrations follow different trends with combinations and permutations of COVID-19 infection and vaccination among healthcare workers in Boston, MA. A majority of HCWs remain well above the positivity threshold for anti-spike RBD IgG antibodies for at least 9 months following vaccin...
Background
Accurate measurement of antibodies is a necessary tool for assessing exposure to SARS-CoV-2 and facilitating understanding of the role of antibodies in immunity. Most assays are qualitative in nature and employ a threshold to determine presence of antibodies. Semi-quantitative assays are now available. Here we evaluate the semi-quantitat...
Background
SARS-CoV-2 continues to spread globally, including in limited resource settings. It is therefore important to derive general case definitions that can be useful and accurate in the absence of timely test results. We aim to validate the World Health Organization (WHO) case definition, a symptom-screening tool currently used to identify SA...
Biorepositories provide a critical resource for gaining knowledge of emerging infectious diseases and offer a mechanism to rapidly respond to outbreaks; the emergence of the novel coronavirus, SARS-CoV-2, has proved their importance. During the COVID-19 pandemic, the absence of centralized, national biorepository efforts meant that the onus fell on...
Background
COVID-19 vaccine trials and post-implementation data suggest vaccination decreases SARS-CoV-2 infections. We examine COVID-19 vaccination’s impact on SARS-CoV-2 case rates and viral diversity among healthcare workers (HCW) during a high community prevalence period.
Methods
A prospective cohort study from Boston Medical Center (BMC)’s HC...
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues. Proteomic, phosphopr...
Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing t...
Healthcare workers (HCWs) are at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that causes Coronavirus Disease (COVID-19). We aim to assess the seroprevalence of SARS-CoV-2 IgG among healthcare workers and compare risk-factors between seropositive and seronegative HCWs. In this observational study,...
Background: COVID-19 vaccine trials and post-implementation data suggest vaccination decreases SARS-CoV-2 infections.
Objective: Estimate COVID-19 vaccinations impact on SARS-CoV-2 case rates and viral diversity among healthcare workers (HCW) during a high community prevalence period.
Design, Setting, Participants: A prospective cohort study from B...
Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events...
We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity...
Coagulation biomarkers are being actively studied for their diagnostic and prognostic value in patients with venous thromboembolism and cancer, as well as in the study of pathogenic mechanisms between cancer and thrombosis. For the results of such studies to be accurate and reproducible, attention must be paid to minimize sources of error in all ph...
Appropriate and diverse representation of minority populations in clinical research studies improves long-term outcomes for all demographics and requires targeted solutions to recruitment challenges. During a two year project at Boston Medical Center (BMC), 191 newly diagnosed, treatment-naïve cancer patients and 76 non-cancer control donors were c...
We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/β-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition,...
Biomarkers are fundamental to basic and clinical research outcomes by reporting host responses and providing insight into disease pathophysiology. Measuring biomarkers with research-use ELISA kits is universal, yet lack of kit standardization and unexpected lot-to-lot variability presents analytic challenges for long-term projects. During an ongoin...
Context.—:
Despite widespread use of formalin-fixed, paraffin-embedded (FFPE) tissue in clinical and research settings, potential effects of variable tissue processing remain largely unknown.
Objective.—:
To elucidate molecular effects associated with clinically relevant preanalytical variability, the National Cancer Institute initiated the Bios...
Biomarkers are fundamental to basic and clinical research outcomes by reporting host responses and providing insight into disease pathophysiology. Measuring biomarkers with research-use ELISA kits is universal, yet lack of kit standardization and unexpected lot-to-lot variability presents analytic challenges for long-term projects. During an ongoin...
Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regula...
We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-β signaling, we found at least one genomic alteration (mutation, homozygous de...
Objective:
Substance P is a neuropeptide that contributes to a pro-inflammatory state by binding to the neurokinin 1 receptor (NK-1R). Limiting this interaction has been shown to attenuate of acute inflammation. Our hypothesis was that NK-1R activation would contribute to the morbidity and mortality of sepsis in a model using mice genetically defi...
Our comprehensive analysis of alternative splicing across 32 The Cancer Genome Atlas cancer types from 8,705 patients detects alternative splicing events and tumor variants by reanalyzing RNA and whole-exome sequencing data. Tumors have up to 30% more alternative splicing events than normal samples. Association analysis of somatic variants with alt...
The link between cancer and thrombosis, especially venous thromboembolism, is well established and thrombotic risk is exacerbated by cancer treatments, such as surgery and chemotherapy. This ongoing study aims to determine the impact of pre-analytic variables (PAVs) on thrombosis biomarkers in a diverse cancer patient and non-cancer subject populat...
Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and p...
Graphical Abstract Highlights d BAP1, PBRM1, and metabolic pathway changes correlate with RCC subtype-specific survival d DNA hypermethylation/CDKN2A alterations associate with poor survival in all RCC subtypes d Immune gene signatures increased in ccRCC and CIMP-RCC d Increased Th2 gene signature within each RCC subtype associates with poorer surv...
We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Ele...
We characterized the epigenetic landscape of genes encoding long noncoding RNAs (lncRNAs) across 6,475 tumors and 455 cancer cell lines. In stark contrast to the CpG island hypermethylation phenotype in cancer, we observed a recurrent hypomethylation of 1,006 lncRNA genes in cancer, including EPIC1 (epigenetically-induced lncRNA1). Overexpression o...
We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macropha...
Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Aneuploidy was anti-correlated with expression of immune signaling genes, du...
We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability case...
The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrat...
Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epi...
Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methyla...
We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reve...
We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predispos...
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this lar...
The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number of expressed enhancers in a genome-wide analysis of 8928 tumor samples across 33 cancer types using TCGA RNA-seq data. Compared with matched normal t...
Identifying molecular cancer drivers is critical for precision oncology. Multiple advanced algorithms to identify drivers now exist, but systematic attempts to combine and optimize them on large datasets are few. We report a PanCancer and PanSoftware analysis spanning 9,423 tumor exomes (comprising all 33 of The Cancer Genome Atlas projects) and us...
The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor-normal exome pairs across 33 different cancer types, in total >400 TB of raw data files requiring analysis. Here we describe the Multi-Center Mutation Calling in Multiple Cancers project, our effort to generate a comprehensive encyclopedia of somatic mutation calls fo...
Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across th...
Biobanks have become an important component of the routine practice of pathology. At the 2016 meeting of the Association of Pathology Chairs, a series of presentations covered several important aspects of biobanking. An often overlooked aspect of biobanking is the fiscal considerations. A biobank budget must address the costs of consenting, procuri...
Neural input to the immune system can alter its ability to clear pathogens effectively. Patients suffering mild traumatic brain injury (mTBI) have shown reduced rates of pneumonia and a murine model replicated these findings, with better overall survival of TBI mice compared with sham-injured mice. To further investigate the mechanism of improved h...
Antimicrobial therapy for sepsis has beneficial effects, but prolonged use fosters emergence of resistant microorganisms, increases cost, and secondary infections. We tested whether 3 days versus 5 days of antibiotics in the murine model of cecal ligation and puncture (CLP) negatively influences outcomes. Following CLP mice were randomized to recei...
Objectives:
Sepsis remains a serious clinical problem despite intensive research efforts and numerous attempts to improve outcome by modifying the inflammatory response. Substance P, the principal ligand for the neurokinin-1 receptor, is a potent proinflammatory mediator that exacerbates inflammatory responses and cardiovascular variables in sepsi...
Objective:
The cause of death in murine models of sepsis remains unclear. The primary purpose of this study was to determine if significant lung injury develops in mice predicted to die after cecal ligation and puncture-induced sepsis compared with those predicted to live.
Design:
Prospective, laboratory controlled experiments.
Setting:
Univer...
The paradigm of systemic inflammatory response syndrome-to-compensatory anti-inflammatory response syndrome transition implies that hyperinflammation triggers acute sepsis mortality, whereas hypoinflammation (release of anti-inflammatory cytokines) in late sepsis induces chronic deaths. However, the exact humoral inflammatory mechanisms attributabl...
Primary Mycobacterium tuberculosis infection results in granuloma formation in lung tissue. A granuloma encapsulates mycobacterium-containing cells, thereby
preventing dissemination and further infection. Tumor necrosis factor alpha (TNF-α) is a host-protective cytokine during M. tuberculosis infection due to its role in promoting and sustaining gr...
Accurate measurement of cytokine concentrations is a powerful and essential approach to the study of inflammation. The enzyme-linked immunosorbent assay (ELISA) is a simple, low-cost analytical tool that provides both the specificity and sensitivity required for the study of cytokines in vitro or in vivo. This communication describes a systematic a...
Immunoreactive signal for the desmosomal protein plakoglobin (γ-catenin) is reduced at cardiac intercalated disks in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a highly arrhythmogenic condition caused by mutations in genes encoding desmosomal proteins. Previously, we observed a false-positive case in which plakoglobin sig...
Citations
... Samples from the SARS-CoV-2 infected groups were obtained from two COVID-19 biorepositories. 31 samples of PCR confirmed inpatients admitted between March to November 2020 were obtained from Boston Medical Center's (BMC) discarded clinical samples biorepository [18]. The remaining SARS-CoV-2 samples were obtained from the Mass General Brigham (MGB) prospective clinical biorepository for patients recruited either in the outpatient clinic or inpatient wards between March and June 2020. ...
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... In the study cited in the letter, which included healthcare workers caring for COVID-19 patients, postvaccination SARS-CoV-2 infection occurred within 14 days of the initial dose in 67 of 7109 (0.9%). 6 These rates are up to five times lower in the clinical trials cited above. 2,3 Even if, in a few cases, we incorrectly classified the disease symptoms as adverse effects of vaccination, this bias would not work in favor of vaccines. ...
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... Increased expression of iASPP has been associated with poor prognosis in multiple cancers, including prostate, melanoma, and glioma [10][11][12]. We thus investigated the association of iASPP mRNA expression and clinical outcomes in two publicly available human PC cohorts (CPTAC-3 [33] and TCGA [34]). No association between OS and iASPP mRNA expression was identified in the CPTAC-3 cohort, and high iASPP levels were associated with poor prognosis in the TCGA cohort, as expected (Fig. 3C). ...
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... To identify and characterize such substitutant peptides, we undertook a large-scale proteomic analysis of multiple cancer types sourced from the CPTAC consortium [8]. To make this analysis more accessible to the scientific community, we developed an online database called ABPEPserver, which harbours substitutant information from eight independent human tumour types, namely Lung Squamous Cell Carcinoma (LSCC, [14]), Clear Cell Renal Cell Carcinoma (CCRCC, [5]), Glioblastoma (GBM, [20]), Head and Neck Squamous Cell Carcinoma (HNSCC, [11]), Hepatocellular Carcinoma (HCC, [9]), Ovarian Sereous Cystadenocarcinoma (OVSCC, [12]), Pancreatic Ductal Carcinoma (PDA, [3]), Uterine Corpus Endometrial Carcinoma (UCEC, [7]). ABPEPserver provides background information on the substitutant peptides and their analyzed cancer type description, a comparative analysis of substitutant expression in tumours and tumour-adjacent normal tissues, and downloadable links of text files harbouring this information. ...
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... (Received 19 January 2023; accepted 22 March 2023) Healthcare personnel (HCP) are considered to be at greater risk for occupational exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection due to their prolonged and frequent exposure to infected patients and unprotected contacts with undiagnosed patients, coworkers, and visitors. [1][2][3][4][5][6] In the early stages of the pandemic prior to the availability of vaccines, the risk of exposure in healthcare setting was high. HCP accounted for 8.8%-13.8% of new COVID-19 cases, according to reports published prior to COVID-19 vaccine availability. ...
... 11 Furthermore, in various reports, it was seen that 85% of breakthrough cases were infected with the B.1.1.7 variant. [12][13][14][15] Similar to our results, Pre-existing illness and age greater than 60 y were found to be predictors of death in unvaccinated patients in a retrospective study on predictors of death in COVID-19 vaccine breakthrough infections in Brazil. 16 ...
... To identify and characterize such substitutant peptides, we undertook a large-scale proteomic analysis of multiple cancer types sourced from the CPTAC consortium [8]. To make this analysis more accessible to the scientific community, we developed an online database called ABPEPserver, which harbours substitutant information from eight independent human tumour types, namely Lung Squamous Cell Carcinoma (LSCC, [14]), Clear Cell Renal Cell Carcinoma (CCRCC, [5]), Glioblastoma (GBM, [20]), Head and Neck Squamous Cell Carcinoma (HNSCC, [11]), Hepatocellular Carcinoma (HCC, [9]), Ovarian Sereous Cystadenocarcinoma (OVSCC, [12]), Pancreatic Ductal Carcinoma (PDA, [3]), Uterine Corpus Endometrial Carcinoma (UCEC, [7]). ABPEPserver provides background information on the substitutant peptides and their analyzed cancer type description, a comparative analysis of substitutant expression in tumours and tumour-adjacent normal tissues, and downloadable links of text files harbouring this information. ...
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... For the analysis of HNSC TIME drivers and their TIME drivers -TIME TFs functional networks, a dataset of 109 HNSC samples from the Clinical Proteomic Tumour Analysis Consortium (CPTAC) [17] with mutation, copy number and gene expression data was downloaded from GDC. These samples were added to the TCGA HNSC cohort for a total of 562 HNSCs. ...
... To identify and characterize such substitutant peptides, we undertook a large-scale proteomic analysis of multiple cancer types sourced from the CPTAC consortium [8]. To make this analysis more accessible to the scientific community, we developed an online database called ABPEPserver, which harbours substitutant information from eight independent human tumour types, namely Lung Squamous Cell Carcinoma (LSCC, [14]), Clear Cell Renal Cell Carcinoma (CCRCC, [5]), Glioblastoma (GBM, [20]), Head and Neck Squamous Cell Carcinoma (HNSCC, [11]), Hepatocellular Carcinoma (HCC, [9]), Ovarian Sereous Cystadenocarcinoma (OVSCC, [12]), Pancreatic Ductal Carcinoma (PDA, [3]), Uterine Corpus Endometrial Carcinoma (UCEC, [7]). ABPEPserver provides background information on the substitutant peptides and their analyzed cancer type description, a comparative analysis of substitutant expression in tumours and tumour-adjacent normal tissues, and downloadable links of text files harbouring this information. ...
... The richness reflects the number of TCRs, while the Shannon diversity index shows the relative abundance of TCRs. The richness and Shannon diversity index of TCR were derived from a previously published study (Thorsson et al. 2018). Single sample GSEA (ssGSEA) was used to calculate the immune cell activity and immune function for each sample. ...
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