- Immune Cell Function and Interaction
- HIV Research and Treatment
- Glioma Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Neuroblastoma Research and Treatments
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- interferon and immune responses
- Advanced biosensing and bioanalysis techniques
- Viral Infections and Immunology Research
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
- Childhood Cancer Survivors' Quality of Life
- Influenza Virus Research Studies
- Viral Infections and Vectors
- CRISPR and Genetic Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Herpesvirus Infections and Treatments
- Ubiquitin and proteasome pathways
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- COVID-19 Clinical Research Studies
- Cell death mechanisms and regulation
- Chromatin Remodeling and Cancer
- Congenital Diaphragmatic Hernia Studies
Broad Institute
2023-2024
Scripps Research Institute
2013-2023
Emmune (United States)
2020-2023
The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology
2023
Johns Hopkins Medicine
2016-2020
Johns Hopkins University
2016-2020
Harvard University
2002-2016
New England Biolabs (United States)
2009-2012
University of Leicester
2009
Beth Israel Deaconess Medical Center
2002-2003
The proteasome inhibitor PS-341 inhibits IκB degradation, prevents NF-κB activation, and induces apoptosis in several types of cancer cells, including chemoresistant multiple myeloma (MM) cells. has marked clinical activity even the setting relapsed refractory MM. However, PS-341-induced apoptotic cascade(s) are not yet fully defined. By using gene expression profiling, we characterized molecular sequelae treatment MM cells further focused on pathways responsible for anticancer actions this...
Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show IFITM restricted entry glycoproteins (GP1,2) of Marburg Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-β specifically filovirus IAV processes. also inhibited replication infectious MARV EBOV. We observed distinct patterns IFITM-mediated...
Histone deacetylases (HDACs) affect cell growth at the transcriptional level by regulating acetylation status of nucleosomal histones. HDAC inhibition induces differentiation and/or apoptosis in transformed cells. We recently showed that inhibitors, such as suberoylanilide hydroxamic acid (SAHA), potently induce human multiple myeloma (MM) In this study, we focused on MM a model to study profile inhibitor treatment tumor cells and address their pathophysiological implications with...
Animal cells use a wide variety of mechanisms to slow or prevent replication viruses. These are usually mediated by antiviral proteins whose expression and activities can be constitutive but frequently amplified interferon induction. Among these interferon-stimulated proteins, members the IFITM (interferon-induced transmembrane) family unique because they infection before virus traverse lipid bilayer cell. At least three human proteins-IFITM1, IFITM2, IFITM3-have activities. limit in...
The generation of humanized BLT mice by the cotransplantation human fetal thymus and liver tissues CD34(+) cells into nonobese diabetic/severe combined immunodeficiency allows for long-term reconstitution a functional immune system, with T cells, B dendritic monocytes/macrophages repopulating mouse tissues. Here, we show that sustained high-level disseminated virus (HIV) infection, resulting in CD4(+) T-cell depletion generalized activation. Following HIV-specific humoral responses were...
Interferon-induced transmembrane (IFITM) proteins are a family of viral restriction factors that inhibit the entry processes several pathogenic viruses, including influenza A virus (IAV), in vitro. Here we report IAV-infected knockout mice lacking Ifitm locus on chromosome 7 exhibited accelerated disease progression, greater mortality, and higher pulmonary systemic burdens as compared to wild type controls. We further observed phenotype Ifitm3-specific was indistinguishable from entire...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme (ACE2). ACE2 is also the viral receptor SARS-CoV (SARS-CoV-1), a related that emerged in 2002–2003. Horseshoe bats (genus Rhinolophus ) are presumed to be original reservoir both viruses, and SARS-like coronavirus, RaTG13, closely SARS-CoV-2, has been identified one horseshoe-bat species. Here we characterize ability S-protein...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCation-dependent transition between the quadruplex and Watson-Crick hairpin forms of d(CGCG3GCG)Charles C. Hardin, Thomas Watson, Matthew Corregan, Charles BaileyCite this: Biochemistry 1992, 31, 3, 833–841Publication Date (Print):January 28, 1992Publication History Published online1 May 2002Published inissue 28 January 1992https://pubs.acs.org/doi/10.1021/bi00118a028https://doi.org/10.1021/bi00118a028research-articleACS PublicationsRequest reuse...
Efforts to control mammalian gene expression with ligand-responsive riboswitches have been hindered by lack of a general method for generating efficient switches in systems. Here we describe rational-design approach that enables rapid development cis-acting aptazyme riboswitches. We identified communication-module characteristics associated functionality through analysis 32-aptazyme test panel. then developed scoring system predicts an aptazymes's activity integrating three bases: hydrogen...
The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike escape neutralization by most therapeutic antibodies. In a pseudovirus assay, 66 the nearly 400 candidate therapeutics Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize multiple sublineages. Among natural immunoglobulin Gs (IgGs), especially those receptor-binding domain (RBD)-2 epitope community, all neutralizers recognize bivalently, with both antigen-binding fragments...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme (ACE2). ACE2 is also the viral receptor SARS-CoV (SARS-CoV-1), a related that emerged in 2002-2003. Horseshoe bats (genus Rhinolophus ) are presumed to be original reservoir both viruses, and SARS-like coronavirus, RaTG13, closely SARS-CoV-2, has been isolated from one horseshoe-bat species. Here we characterize ability S-protein...
Standard treatment for the majority of malignant brain tumours consists surgery and radiotherapy. This has late morbidity which is accentuated in very young child. As part a strategy to improve quality life overall survival children with tumours, members United Kingdom Children9s Cancer Study Group (UKCCSG) have piloted an intensive chemotherapy regimen aims avoid or delay radiotherapy following surgery. Twenty eight variety received regimen, contains carboplatin, vincristine,...
Ovarian pathology is an important cause of decreased fertility and reproductive capability may impact multiple systems, particularly in aging rhesus macaques.Retrospective histopathologic immunohistochemical analysis 458 female macaque necropsies over 12 years at the New England Primate Research Center Southborough, MA.Degenerative inflammatory changes ovaries included mineralization, infiltration by lymphocytes, macrophages multinucleated giant cells, endometriosis, arteriopathy. Cystic...
The rhesus macaque ( Macaca mulatta) is used extensively in translational biomedical research and drug development studies an important model of aging. Macaques often develop myocardial fibrosis with age, which can result the loss normal cardiac architecture expansion extracellular matrix deposition collagen. etiology pathogenesis this pernicious process poorly understood. Cardiac was assessed using histologic immunohistochemical techniques tissue sections from 34 macaques. Overall left...
Adeno-associated virus (AAV) is one of the most commonly used vectors for gene therapy, and applications AAV-delivered therapies are numerous. However, current state technology limited by low efficiency with which AAV transduce skeletal muscle tissue. We demonstrate that vector can be enhanced modifying capsid a peptide binds receptor highly expressed in When an insulin-mimetic peptide, S519, previously characterized its high affinity to insulin (IR), was inserted into capsid, AAV9...