A5102006659- Immune Cell Function and Interaction
- Systemic Sclerosis and Related Diseases
- Tuberculosis Research and Epidemiology
- Cell death mechanisms and regulation
- Monoclonal and Polyclonal Antibodies Research
- RNA Research and Splicing
- Mycobacterium research and diagnosis
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Immune responses and vaccinations
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Bacillus and Francisella bacterial research
- Bacterial Identification and Susceptibility Testing
- Microbial infections and disease research
- interferon and immune responses
- Ubiquitin and proteasome pathways
- Cancer Mechanisms and Therapy
- Eosinophilic Disorders and Syndromes
- Toxin Mechanisms and Immunotoxins
- Glycosylation and Glycoproteins Research
- NF-κB Signaling Pathways
- Muscle Physiology and Disorders
- Blood properties and coagulation
- Facial Rejuvenation and Surgery Techniques
Animal and Plant Health Agency
2019-2025
Genomics Institute of the Novartis Research Foundation
2009
Brigham and Women's Hospital
1997-2007
Harvard University
1994-2007
Dana-Farber Cancer Institute
1991-1997
Dana-Farber Brigham Cancer Center
1997
University of Toronto
1989
The trichothecene family of mycotoxins inhibit protein synthesis by binding to the ribosomal peptidyltransferase site. Inhibitors reaction (e.g.anisomycin) can trigger a ribotoxic stress response that activates c-Jun N-terminal kinase (JNK)/p38 mitogen-activated kinases, components signaling cascade regulates cell survival in stress. We have found selected trichothecenes strongly activate JNK/p38 kinases and induce rapid apoptosis Jurkat T cells. Although ability individual are dissociable,...
Proteins cleaved by interleukin-1β converting enzyme family proteases during apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus (SLE). We have tested the possibility that proteins phosphorylated cells undergoing also autoimmune disease. Sera from 9/12 containing antinuclear antibodies (10/12 meeting diagnostic criteria SLE or a overlap syndrome), precipitated new phosphoproteins lysates derived Jurkat T treated apoptotic stimuli (i.e.,...
We have identified a serine/threonine kinase that is rapidly activated during Fas-mediated apoptosis. Fas-activated (FAST) phosphorylated on serine and threonine residues in Jurkat cells. In response to Fas ligation, it dephosphorylated concomitantly phosphorylate TIA-1, nuclear RNA-binding protein has been implicated as an effector of Phosphorylation TIA-1 precedes the onset DNA fragmentation, suggesting role signaling downstream events apoptotic program. Our results introduce Fast...
NK cells are large granular lymphocytes capable of killing certain tumor and virally infected in a non-MHC-restricted manner. can also effect an antibody dependent cytotoxicity that is triggered by CD16, FcR for IgG. In cells, CD16 expressed association with zeta, signal transducing subunit the TCR complex. Here we show that, just as T cell activation via complex results tyrosine phosphorylation zeta TCR, NK. Whereas antibody-dependent natural does not. Our indicate functions element...
Abstract Activation‐induced natural killer (NK) cell death is very rapid compared to activation‐induced T or B death. Here we show that NK activation accompanied by the leakage of granzymeB from intracellular granules into cytoplasm. Evidence for granzyme includes formation B/serine proteinase inhibitor 9 (PI‐9) complexes are detected immunoprecipitation as well colocalization and PI‐9 immunocytochemistry. The pro‐apoptotic molecule Bid, a specific substrate B, was cleaved within 2 min...
In the UK and Ireland, European badger is main wildlife reservoir for Mycobacterium bovis (M. bovis), causal agent of bovine tuberculosis (bTB). The ability to diagnose M. infection in badgers critical understanding epidemiology this species informing control strategies. study we determined sensitivity specificity a lateral flow assay (Dual Path Platform (DPP) VetTB assay) identify infected live using two blood sample types: fresh whole (suitable immediate testing field without further...
Using human autoimmune sera as molecular probes, we previously described the association of phosphorylated serine/arginine splicing factors (SR factors) with U1-small nuclear ribonucleoprotein (U1-snRNP) and U3-small nucleolar RNP (snoRNP) in apoptotic cells. SR proteins are highly conserved autoantigens whose activity is tightly regulated by reversible phosphorylation serine residues at least eight different protein kinase kinases (SRPKs), including SRPK1, SRPK2, scleroderma autoantigen...
One therapeutic approach to Duchenne Muscular Dystrophy (DMD) recently entering clinical trials aims convert DMD phenotypes that of a milder disease variant, Becker (BMD), by employing antisense oligonucleotides (AONs) targeting splice sites, induce exon skipping and restore partial dystrophin function. In order search for small molecule genetic modulators AON-dependent independent skipping, we screened approximately 10,000 known drugs, >17,000 cDNA clones, >2,000 kinase- targeted siRNAs...
Bovine tuberculosis (bTB), caused by Mycobacterium bovis, represents a major animal health issue. In the United Kingdom and Republic of Ireland, European badgers (Meles meles) have been shown to act as reservoir M. bovis infection, hindering eradication bTB in livestock. The availability suitable diagnostic assays, particularly those that may be applied "trap-side" setting, would facilitate implementation wider range disease control strategies. Here we evaluate Dual Path Platform (DPP) VetTB...
Abstract European badgers ( Meles meles ) have been identified as wildlife reservoirs for Mycobacterium bovis in the UK and Ireland, may also a role epidemiology of animal tuberculosis other regions. Thus, detection M. ‐infected be required purposes surveillance monitoring disease levels infected populations. Current serological assays to detect infection live badgers, while rapid inexpensive, show limited diagnostic sensitivity. Here we describe evaluate new ELISA platforms recognition P22...
Oral vaccination with Mycobacterium bovis Bacille of Calmette and Guerin (BCG) has provided protection against M. to badgers both experimentally in the field. There is also evidence suggesting that persistence live BCG within host important for maintaining TB. Here we investigated capacity badger inductive mucosal sites absorb maintain BCG. The targeted mucosae were oropharyngeal cavity (tonsils sublingual area) small intestine (ileum). We showed significant quantities persisted tissues...
Objective Proteins that are phosphorylated during apoptosis commonly precipitated by autoantibodies found in the sera of patients with systemic lupus erythematosus. We sought to determine whether scleroderma autoantigens such as small nucleolar RNPs (snoRNP) also associate phosphoproteins response various cellular stressors. Methods screened a panel monoclonal antibodies derived from mice exposed mercury, well-characterized murine model anti-snoRNP autoimmune response, for ability...
CD94 (Kp43) is a member of the human C-type lectin superfamily encoding type II membrane glycoproteins expressed on NK cells and subset T cells. Ligation has been shown to either potentiate or inhibit cell proliferation cytolytic effector function. Here we show that ligation triggers apoptosis in IL-2-primed Evidence for CD94-induced includes: 1) chromatin condensation as measured by increased fluorescence Hoechst dye, 2) induction DNA fragmentation, 3) characteristic morphology transmission...
Abstract The CD3‐T cell receptor (TCR) complex on T cells and the Fcγ type III (FcγRIII)‐ζ‐γ natural killer are functionally analogous activation receptors that associate with a family of disulfide‐linked dimers composed related subunits ζ γ. Immunochemical analysis complexes separated two‐dimensional diagonal gels allowed identification previously uncharacterized ζ‐p14 heterodimer. is component both CD3‐TCR FcγRIII‐ζ‐γ. Peptide mapping shows p14 structurally to ζ, suggesting it either: (i)...