A5045281805- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- NF-κB Signaling Pathways
- Cell death mechanisms and regulation
- dental development and anomalies
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Chronic Lymphocytic Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- Immunodeficiency and Autoimmune Disorders
- Cancer-related gene regulation
- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Chronic Myeloid Leukemia Treatments
- Wnt/β-catenin signaling in development and cancer
- Proteoglycans and glycosaminoglycans research
- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune cells in cancer
- Chemokine receptors and signaling
- Toxin Mechanisms and Immunotoxins
University of Lausanne
2016-2025
AstraZeneca (Sweden)
2023-2024
QIMR Berghofer Medical Research Institute
2023
Weatherford College
2023
The University of Melbourne
1994-2023
Australian Regenerative Medicine Institute
2023
Monash University
2009-2023
Royal Brisbane and Women's Hospital
2023
AstraZeneca (Australia)
2023
Centro Científico Tecnológico - Patagonia Norte
2023
The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production tumor necrosis factor (TNF) family members appears to be important in cases. BAFF, a new member the TNF family, binds B cells costimulates their growth vitro. Mice transgenic for BAFF have vastly increased numbers mature effector T cells, develop autoimmune-like manifestations such as presence high levels rheumatoid factors, circulating immune complexes, anti–DNA autoantibodies,...
Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member TNF family, designated BAFF (for B activating belonging to family), which is expressed by T cells dendritic cells. Human was mapped chromosome 13q32-34. Membrane-bound processed secreted through action protease whose specificity matches that furin proprotein convertases. The expression receptor appeared be...
Malignant melanoma accounts for most of the increasing mortality from skin cancer. Melanoma cells were found to express Fas (also called Apo-1 or CD95) ligand (FasL). In metastatic lesions, Fas-expressing T cell infiltrates proximal FasL+ tumor cells. vitro, apoptosis Fas-sensitive target occurred upon incubation with cells; and in vivo, injection mouse mice led rapid formation. contrast, tumorigenesis was delayed Fas-deficient lpr mutant which immune effector cannot be killed by FasL. Thus,...
B cell homeostasis has been shown to critically depend on BAFF, the activation factor from tumor necrosis (TNF) family. Although BAFF is already known bind two receptors, BCMA and TACI, we have identified a third receptor for that termed BAFF-R. BAFF-R binding appears be highly specific suggesting unique role this ligand-receptor interaction. Consistent with this, locus disrupted in A/WySnJ mice, which display phenotype qualitatively similar of BAFF-deficient mice. Thus, principal...
BAFF (BLyS, TALL-1, THANK, zTNF4) is a member of the TNF superfamily that specifically regulates B lymphocyte proliferation and survival. Mice transgenic (Tg) for develop an autoimmune condition similar to systemic lupus erythematosus. We now demonstrate Tg mice, as they age, secondary pathology reminiscent Sjögren's syndrome (SS), which manifested by severe sialadenitis, decreased saliva production, destruction submaxillary glands. In humans, SS also correlates with elevated levels...
Human Fas ligand (L) (CD95L) and tumor necrosis factor (TNF)-alpha undergo metalloproteinase-mediated proteolytic processing in their extracellular domains resulting the release of soluble trimeric ligands (soluble [s]FasL, sTNF-alpha) which, case sFasL, is thought to be implicated diseases such as hepatitis AIDS. Here we show that sFasL occurs between Ser126 Leu127. The apoptotic-inducing capacity naturally processed was reduced by >1,000-fold compared with membrane-bound FasL, injection...
B cell maturation is a very selective process that requires finely tuned differentiation and survival signals. activation factor from the TNF family (BAFF) member binds to cells potentiates receptor (BCR)-mediated proliferation. A role for BAFF in was suggested by observation of reduced peripheral numbers mice treated with reagents blocking BAFF, high Bcl-2 levels detected transgenic (Tg) mice. We tested vitro effect on lymphocytes derived primary secondary lymphoid organs. induced subset...
BAFF (BLyS, TALL-1, THANK, zTNF4) is a member of the TNF superfamily that specifically regulates B lymphocyte proliferation and survival. Mice transgenic (Tg) for develop an autoimmune condition similar to systemic lupus erythematosus. We now demonstrate Tg mice, as they age, secondary pathology reminiscent Sjögren’s syndrome (SS), which manifested by severe sialadenitis, decreased saliva production, destruction submaxillary glands. In humans, SS also correlates with elevated levels...
MyD88 has a modular organization, an N-terminal death domain (DD) related to the cytoplasmic signaling domains found in many members of tumor necrosis factor receptor (TNF-R) superfamily, and C-terminal Toll similar that expanding family Toll/interleukin-1-like receptors (IL-1R). This dual structure, together with following observations, supports role for as adapter IL-1 signal transduction; forms homodimers vivo through DD-DD Toll-Toll interactions. Overexpression induces activation c-Jun...
Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member TNF designated APRIL (for proliferation-inducing ligand). Although transcripts are low abundance in normal tissues, high levels mRNA detected transformed lines, human cancers colon, thyroid, lymphoid tissues vivo. The addition recombinant to various cells stimulates their proliferation. Moreover, APRIL-transfected...
Death receptors, such as Fas and tumor necrosis factor-related apoptosis-inducing ligand recruit Fas-associated death domain pro-caspase-8 homodimers, which are then autoproteolytically activated. Active caspase-8 is released into the cytoplasm, where it cleaves various proteins including pro-caspase-3, resulting in apoptosis. The cellular domain-like interleukin-1-β-converting enzyme-inhibitory protein long form (FLIPL), a structural homologue of lacking caspase activity because several...
Ligands of the tumor necrosis factor superfamily (TNFSF) (4-1BBL, APRIL, BAFF, CD27L, CD30L, CD40L, EDA1, EDA2, FasL, GITRL, LIGHT, lymphotoxin alpha, alphabeta, OX40L, RANKL, TL1A, TNF, TWEAK, and TRAIL) bind members TNF receptor (TNFRSF). A comprehensive survey ligand-receptor interactions was performed using a flow cytometry-based assay. All ligands engaged between one five receptors, whereas most receptors only bound to three ligands. The DR6, RELT, TROY, NGFR, mouse TNFRH3 did not...
The membrane-bound form of Fas ligand (FasL) signals apoptosis in target cells through engagement the death receptor Fas, whereas proteolytically processed, soluble FasL does not induce cell death.However, can be rendered active upon cross-linking.Since minimal extent oligomerization that exerts cytotoxicity is unknown, we engineered hexameric proteins containing two trimers within same molecule.This was achieved by fusing to Fc portion immunoglobulin G1 or collagen domain...