A5061316293- SARS-CoV-2 and COVID-19 Research
- Research on Leishmaniasis Studies
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- Epigenetics and DNA Methylation
- Immune cells in cancer
- Parasites and Host Interactions
- Cancer-related Molecular Pathways
- Trypanosoma species research and implications
- Animal Virus Infections Studies
- interferon and immune responses
- Vaccine Coverage and Hesitancy
- vaccines and immunoinformatics approaches
- RNA modifications and cancer
- Immune Response and Inflammation
- Genomics and Chromatin Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Extracellular vesicles in disease
- Trace Elements in Health
- Air Quality and Health Impacts
- Cytokine Signaling Pathways and Interactions
- Phagocytosis and Immune Regulation
- MicroRNA in disease regulation
- Viral Infections and Outbreaks Research
- Metabolomics and Mass Spectrometry Studies
Massachusetts General Hospital
2018-2024
Harvard University
2008-2024
Brigham and Women's Hospital
2017
McGill University Health Centre
2005-2008
McGill University
2004-2007
University of Dundee
2001-2005
Université Laval
2005
John Radcliffe Hospital
2001
University of Oxford
2001
Wellcome Trust
2001
Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence variants harboring mutations in spike, main target antibodies. To understand impact these variants, we evaluated neutralization potency 99 individuals that received one or two doses either BNT162b2 mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains Five pseudoviruses, receptor-binding domain mutations, including K417N/T,...
SUMMARY Recent surveillance has revealed the emergence of SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, target vaccine-induced neutralizing antibodies. Given its potential escape humoral immunity, we measured neutralization potency sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild type, Delta, pseudoviruses. We included individuals that were vaccinated recently (<3 months), distantly (6-12 or boosted,...
Abstract Background p68 (Ddx5) and p72 (Ddx17) are highly related members of the DEAD box family established RNA helicases. They have been implicated in growth regulation shown to be involved both pre-mRNA pre-rRNA processing. More recently, however, these proteins reported act as transcriptional co-activators for estrogen-receptor alpha (ERα). Furthermore were interact with p300/CBP polymerase II holoenzyme. Taken together reports suggest a role activation. Results In this report we show...
Leishmania spp. are obligate intracellular parasites that inhabit the phagolysosomes of macrophages. Manipulation host cell signaling pathways and gene expression by is critical for Leishmania's survival resultant pathology. Here, we show infection macrophages with promastigotes in vitro causes specific cleavage NF-kappaB p65 RelA subunit. Cleavage occurs cytoplasm dependent on protease gp63. The resulting fragment, p35 RelA, migrates to nucleus, where it binds DNA as a heterodimer p50....
In order to survive within the macrophages of its host organism, protozoan parasite Leishmania inhibits a number critical, gamma interferon (IFN-gamma)-inducible, macrophage functions, including generation nitric oxide. We have previously shown that protein tyrosine phosphatase SHP-1 (Src-homology 2 domain containing phosphatase-1) is activated during infection and plays an important role in both survival cultured disease progression vivo by inhibiting oxide production. Here we use SHP-1-/-...
Exposure to environmental particles during pregnancy increases asthma susceptibility of the offspring. We tested hypothesis that this transmission continues F2 and F3 generations occurs via epigenetic mechanisms. compared allergic three BALB/c offspring after a single maternal exposure diesel exhaust or concentrated urban air particles. After pregnant dams received intranasal instillations particle suspensions control, their F1, F2, were in low-dose ovalbumin protocol for sensitivity asthma....
Recent surveillance has revealed the emergence of SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, target vaccine-induced neutralizing antibodies. Given its potential escape humoral immunity, we measured neutralization potency sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild type, Delta, pseudoviruses. We included individuals that were vaccinated recently (<3 months), distantly (6-12 or boosted, accounted for...
The intracellular parasite Leishmania causes a wide spectrum of human disease, ranging from self-resolving cutaneous lesions to fatal visceral depending on the species involved. mechanisms by which different cause pathologies are largely unknown. We have addressed this question comparing gene expression profiles bone marrow-derived macrophages infected with either donovani or L. major promastigotes. found that two had very similar effects macrophage expression. Both caused small (<2.5-fold)...
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Abstract Background Understanding immunogenicity and effectiveness of SARS-CoV-2 vaccines is critical to guide rational use. Methods We compared the mRNA-1273, BNT-162b2 or Ad26.COV2.S in ambulatory adults Massachusetts, USA. To correlate with three vaccines, we performed an inverse-variance meta-analysis population level from public health reports >40 million individuals. Results A single dose either mRNA vaccine yielded comparable antibody neutralization titers convalescent lower...
Activation of the Janus-activated kinase 2 (JAK2)/STAT1alpha signaling pathway is repressed in Leishmania-infected macrophages. This represents an important mechanism by which this parasite subverts microbicidal functions cell to promote its own survival and propagation. We recently provided evidence that protein tyrosine phosphatase (PTP) SHP-1 was responsible for JAK2 inactivation. However, STAT1 translocation nucleus not restored absence SHP-1. In present study, we have used B10R...
The ability to specifically reactivate epigenetically silenced genes would have great utility in experimental studies and potential therapeutic value. Here, we describe the specific targeting of thymidine DNA glycosylase (TDG), an enzyme involved mechanism methylcytosine demethylation, promoter Nos2, a gene by methylation fibroblasts, using artificial zinc finger binding domains. Individual targeted TDG constructs had small effect on Nos2 expression methylation, but simultaneous quartet...
SUMMARY Since the COVID-19 pandemic began in 2020, viral sequencing has documented 131 individual mutations spike protein across 48 named variants. To determine ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution, we assessed neutralization potency sera from 76 vaccine recipients collected after 2 6 immunizations against a comprehensive panel observed during pandemic. Remarkably, while many that emerged between 2020 and 2022 exhibit escape following...
Our ability to selectively manipulate gene expression by epigenetic means is limited, as there no approach for targeted reactivation of epigenetically silenced genes, in contrast what available selective silencing. We aimed develop a tool transcriptional activation DNA demethylation. Here we present evidence that direct targeting thymine-DNA-glycosylase (TDG) specific sequences the can result local demethylation at potential regulatory and lead enhanced induction. When TDG was fused...
Antibodies to SARS-CoV-2 are central recovery and immunity from COVID-19. However, the relationship between disease severity repertoire of antibodies against specific epitopes an individual develops following exposure remains incompletely understood. Here, we studied seroprevalence other betacoronavirus antigens in a well-annotated, community sample convalescent never-infected individuals obtained August 2020. One hundred twenty-four participants were classified into five groups: previously...
Interferon-gamma (IFN-γ) inhibits intracellular replication of Francisella tularensis in human monocyte-derived macrophages (HMDM) and mice, but the mechanisms this protective effect are poorly characterized. We used genome-wide RNA interference (RNAi) screening macrophage cell line THP-1 to identify genes that mediate beneficial effects IFN-γ on F. infection. A primary screen identified ∼200 replicated candidate genes. These were prioritized according mRNA expression IFN-γ-primed...