A5000780125- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- S100 Proteins and Annexins
- Influenza Virus Research Studies
- Cutaneous lymphoproliferative disorders research
- Respiratory viral infections research
- T-cell and Retrovirus Studies
- Animal Virus Infections Studies
- Glycosylation and Glycoproteins Research
- Viral gastroenteritis research and epidemiology
- Cell death mechanisms and regulation
- Phagocytosis and Immune Regulation
- Cell Adhesion Molecules Research
- RNA Interference and Gene Delivery
- Viral Infectious Diseases and Gene Expression in Insects
- Vector-Borne Animal Diseases
- Antimicrobial Peptides and Activities
- Protein purification and stability
- CRISPR and Genetic Engineering
Dana-Farber Cancer Institute
2016-2025
Harvard University
2014-2024
Harvard University Press
2000-2016
Harvard Affiliated Emergency Medicine Residency
2015
Boston University
2005-2014
Dana-Farber Brigham Cancer Center
2012
Brigham and Women's Hospital
1989-2012
Tel Aviv University
2011
National Center for Infectious Diseases
2004
Centers for Disease Control and Prevention
2004
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East (MERS)-CoV underscores the threat cross-species transmission events leading to outbreaks in humans. Here we examine disease potential a SARS-like virus, SHC014-CoV, which is currently circulating Chinese horseshoe bat populations. Using SARS-CoV reverse genetics system, generated characterized chimeric virus expressing spike SHC014 mouse-adapted backbone. results indicate that group 2b viruses encoding...
The 2009 pandemic H1N1 influenza demonstrated the global health threat of reassortant strains. Herein, we report a detailed analysis plasmablast and monoclonal antibody responses induced by infection in humans. Unlike antibodies elicited annual vaccinations, most neutralizing were broadly cross-reactive against epitopes hemagglutinin (HA) stalk head domain multiple from cells that had undergone extensive affinity maturation. Based on these observations, postulate plasmablasts producing...
Effective prophylaxis and antiviral therapies are urgently needed in the event of reemergence highly contagious often fatal severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) infection. We have identified eight recombinant human single-chain variable region fragments (scFvs) against S1 domain spike (S) protein SARS-CoV from two nonimmune antibody libraries. One scFv 80R efficiently neutralized inhibited syncytia formation between cells expressing S those receptor...
Chemotactic factor-enriched butanol extracts from Escherichia coli culture filtrates were fractionated and purified by high pressure liquid chromatography. The yield individual fractions of biological activity (lysosomal enzyme secretion) antigenic (competition with [3H]fMet-Leu-Phe for binding to rabbit anti-fMet-Leu-Phe) revealed an average 50% recovery original material. Five peaks separated as demonstrated enzyme-releasing activity. Three these coincided exactly activity, suggesting that...
Outbreaks from zoonotic sources represent a threat to both human disease as well the global economy. Despite wealth of metagenomics studies, methods leverage these datasets identify future threats are underdeveloped. In this study, we describe an approach that combines existing data with reverse genetics engineer reagents evaluate emergence and pathogenic potential circulating viruses. Focusing on severe acute respiratory syndrome (SARS)-like viruses, results indicate WIV1-coronavirus (CoV)...
Advances in the treatment of metastatic clear cell renal carcinoma (ccRCC) have led to improved progression-free survival many patients; however therapies are toxic, rarely achieve durable long-term complete responses and not curative. Herein we used a single bicistronic lentiviral vector develop new combination immunotherapy that consists human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered secrete anti-programmed death ligand 1 (PD-L1)...
Human coronavirus (hCoV) HKU1 is one of six hCoVs identified to date and the only with an unidentified cellular receptor. hCoV-HKU1 encodes a hemagglutinin-esterase (HE) protein that unique group betacoronaviruses (group 2a). The function HKU1-HE remains largely undetermined. In this study, we examined binding S1 domain spike panel cells found could specifically bind on cell surface human rhabdomyosarcoma line, RD. Pretreatment RD neuraminidase (NA) trypsin greatly reduced binding,...
Significance The recently emerged Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe respiratory disease with ∼43% mortality. There is no licensed vaccine or antiviral for MERS. Here we identified seven human neutralizing Abs (nAbs) against MERS-CoV. These nAbs bind to three epitope groups in the viral Spike protein–receptor interface, blocking virus attachment. Five residues receptor-binding domain critical neutralization escape were identified. Further study indicated...
Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute distress (ARDS), severe pneumonia-like symptoms and multi-organ failure, with case fatality rate of ∼36%. Limited clinical studies indicate humans infected MERS-CoV exhibit pathology consistent the late stages ARDS, which reminiscent disease observed patients coronavirus. Models MERS-CoV-induced have been difficult to achieve, small-animal models traditionally used investigate viral...
Abstract IGHV polymorphism provides a rich source of humoral immune system diversity. One important example is the IGHV1-69 germline gene where biased use alleles that encode critical CDR-H2 Phe54 (F-alleles) to make broadly neutralizing antibodies (HV1-69-sBnAb) influenza A hemagglutinin stem domain has been clearly established. However, whether can also modulate B cell function and Ab repertoire expression through promoter copy number (CN) variations not reported, nor allelic distribution...
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 21 million people worldwide since August 16, 2020. Compared to PCR and serology tests, SARS-CoV-2 antigen assays are underdeveloped, despite their potential identify active infection monitor disease progression. Methods We used Single Molecule Array (Simoa) quantitatively detect spike, S1 subunit, nucleocapsid antigens in the plasma of patients with (COVID-19). studied from 64 who were COVID-19...
Variation in the antibody response has been linked to differential outcomes disease, and suboptimal vaccine therapeutic responsiveness, determinants of which have not fully elucidated. Countering models that presume antibodies are generated largely by stochastic processes, we demonstrate polymorphisms within immunoglobulin heavy chain locus (IGH) impact naive antigen-experienced repertoire, indicating genetics predisposes individuals mount qualitatively quantitatively different responses. We...
A single-chain antibody, derived from a human monoclonal antibody that recognizes the CD4 binding region of immunodeficiency virus type 1 (HIV-1) envelope protein, has been designed for intracellular expression in eukaryotic cells. The is composed an immunoglobulin heavy-chain leader sequence and heavy- light-chain variable regions are joined by interchain linker. stably expressed retained endoplasmic reticulum not toxic to binds protein within cell inhibits processing precursor syncytia...
Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS novel coronavirus (SARS-CoV). coronaviral surface spike protein S type I transmembrane glycoprotein mediates initial host binding via the cell receptor angiotensin-converting enzyme 2 (ACE2), as well subsequent membrane fusion events required for entry. Here we report crystal structure S1 domain (RBD) complex with neutralizing antibody, 80R, at 2.3...
West Nile virus, a member of the Flavivirus genus, causes fever that can progress to life-threatening encephalitis. The major envelope glycoprotein, E, these viruses mediates viral attachment and entry by membrane fusion. We have determined crystal structure soluble fragment virus E. adopts same overall fold as E proteins from dengue tick-borne encephalitis viruses. conformation domain II is different in other prefusion structures, however, resembles postfusion structures. epitopes...
Eighty-eight cases of group C streptococcal bacteremia were reviewed retrospectively. Most patients had underlying diseases (72.7%), predominantly cardiovascular disease (20.5%)or malignancy (20.5%). The infection originated most often from the upper respiratory tract (20.5%), gastrointestinal (18.2%), or skin (17.1%). Prior exposure to animals animal products was reported in 23.9% cases. common clinical manifestations endocarditis (27.3%), primary (22.7%), and meningitis (10.2%). Of...
Enveloped viruses use multiple mechanisms to inhibit infection of a target cell by more than one virion. These may be particular importance for the evolution segmented viruses, because superinfection exclusion limit frequency reassortment viral genes. Here, we show that cellular expression influenza A virus neuraminidase (NA), but not hemagglutinin (HA) or M2 proton pump, inhibits entry HA-pseudotyped retroviruses. Cells infected with H1N1 H3N2 were similarly refractory HA-mediated and...