A5057037971- Psoriasis: Treatment and Pathogenesis
- Cytokine Signaling Pathways and Interactions
- Bartonella species infections research
- Toxin Mechanisms and Immunotoxins
- Monoclonal and Polyclonal Antibodies Research
- Protein Hydrolysis and Bioactive Peptides
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- Melanoma and MAPK Pathways
- Ubiquitin and proteasome pathways
- NF-κB Signaling Pathways
- Whipple's Disease and Interleukins
- Banana Cultivation and Research
- Angiogenesis and VEGF in Cancer
- Peptidase Inhibition and Analysis
- Immune Cell Function and Interaction
- Enzyme Structure and Function
- Biochemical effects in animals
- Signaling Pathways in Disease
- Enzyme Production and Characterization
- Autophagy in Disease and Therapy
- IL-33, ST2, and ILC Pathways
- Studies on Chitinases and Chitosanases
- Galectins and Cancer Biology
Novartis (Switzerland)
2009-2022
University of Basel
2011-2021
Galapagos (France)
2020
University of Antwerp
2016
Novartis Institutes for BioMedical Research
2009-2015
Federal Institute for Occupational Safety and Health
1996
Toxin-antitoxin (TA) modules are ubiquitous molecular switches controlling bacterial growth via the release of toxins that inhibit cell proliferation. Most these interfere with protein translation, but a growing variety other mechanisms hints at diversity is not yet fully appreciated. Here, we characterize group FIC domain proteins as conserved and abundant FicTA family TA modules, reveal they act by suspending control cellular DNA topology. We show FicTs enzymes adenylylate gyrase...
IL-17A and IL-17F are prominent members of the IL-17 family cytokines that regulates both innate adaptive immunity. has been implicated in chronic inflammatory autoimmune diseases, anti-IL-17A antibodies have shown remarkable clinical efficacy psoriasis psoriatic arthritis patients. homodimeric can also form IL-17A/F heterodimer whose precise role health disease remains elusive. All three signal through assembly a ternary complex with IL-17RA IL-17RC receptors. Here we report X-ray analysis...
p53 tumor suppressor activity is negatively regulated through binding to the oncogenic proteins Hdm2 and HdmX. The residues Leu(26), Trp(23), Phe(19) are crucial mediate these interactions. Inhibiting both HdmX should be a promising clinical approach reactivate in cancer setting, but previous studies have suggested that discovery of dual Hdm2/HdmX inhibitors will difficult. We determined crystal structures at 1.3 A N-terminal domain bound two peptidomimetics without with 6-chlorine...
Abstract Numerous bacterial pathogens subvert cellular functions of eukaryotic host cells by the injection effector proteins via dedicated secretion systems. The type IV system (T4SS) protein BepA from Bartonella henselae is composed an N‐terminal Fic domain and a C‐terminal intracellular delivery domain, latter being responsible for T4SS‐mediated translocation into cells. A proteolysis resistant fragment (residues 10–302) that includes shows autoadenylylation activity adenylyl transfer onto...
ISB 1442 is a bispecific biparatopic antibody in clinical development to treat hematological malignancies. It consists of two adjacent anti-CD38 arms targeting non-overlapping epitopes that preferentially drive binding tumor cells and low-affinity anti-CD47 arm enable avidity-induced blocking proximal CD47 receptors. We previously reported the pharmacology 1442, designed reestablish synthetic immunity CD38+ Here, we describe discovery, optimization characterization antigen fragment (Fab)...
This paper describes the identification of 6-(pyrimidin-4-yloxy)-naphthalene-1-carboxamides as a new class potent and selective human vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitors. In biochemical cellular assays, compounds exhibit single-digit nanomolar potency toward VEGFR2. Compounds this series show good exposure in rodents when dosed orally. They potently inhibit VEGF-driven angiogenesis chamber model rodent tumor models at daily doses less than 3...
Signaling through innate immune receptors such as the Toll-like receptor (TLR)/interleukin-1 (IL-1R) superfamily proceeds via assembly of large membrane-proximal complexes or "signalosomes." Although structurally distinct, IL-17 family triggers cellular responses that are typical receptors. The IL-17RA subunit is shared by several members family. Using a combination crystallographic, biophysical, and mutational studies, we show IL-17A, IL-17F, IL-17A/F induce dimerization. X-ray analysis...
The ubiquitous FIC domain is evolutionarily conserved from bacteria to human and has been shown catalyze AMP transfer onto protein side-chain hydroxyl groups. Recently, it was predicted that most catalytically competent Fic proteins are inhibited by the presence of an inhibitory helix αinh provided a cognate anti-toxin (class I), or part N- C-terminal itself (classes II III). In vitro, inhibition relieved mutation glutamate glycine. For class III bacterial NmFic Neisseria meningitidis,...
Small GTPases of the Ras-homology (Rho) family are conserved molecular switches that control fundamental cellular activities in eukaryotic cells. As such, they targeted by numerous bacterial toxins and effector proteins, which have been intensively investigated regarding their biochemical discrete target spectra; however, mechanism selectivity has remained largely elusive. Here we report a protein selectively targets members Rac subfamily Rho small but none closely related Cdc42 or RhoA...
Abstract Semi‐preparative isolation of casein phosphopeptides (CPP) from a tryptic hydrolysate bovine was performed applying three‐step procedure consisting solid phase extraction, reversed HPLC and ion exchange chromatography. Dephosphorylation CPP achieved using immobilized alkaline phosphatase. The purified their dephosphorylated forms obtained by these methods are suitable for comparative studies on biological activities, especially mineral binding immunmodulation.
Abstract Antibody-cytokine conjugates leverage orthogonal mechanisms of action (MoA) in one molecule to induce potent antitumor immune responses. PD-1-targeting are particular interest since they preferentially target antigen-experienced PD-1+ CD8+ T cells enriched the tumor microenvironment (TME) while simultaneously blocking PD-(L)1 pathway and inducing cytokine receptor stimulation same cell cis (cis-signaling). Interleukin 18 (IL-18) is a proinflammatory able integrate both innate...
<h3>Background</h3> Immunocytokines provide the opportunity to simultaneously address distinct and complementary mechanisms of action deliver cytokine payloads specific immune cells ('cis-signaling') resulting in enhanced anti-tumor activity. However, there is increasing evidence that use constitutively active IL-2 payload limits therapeutic index PD1-IL2 immunocytokines due systemic toxicity from potent induced cell activation release pro-inflammatory cytokines periphery. <h3>Methods</h3>...
The present paper reports on studies concerned with furnishing evidence for peptide synthesis in the course of vitro proteolysis. To this end, oxidized chain B from insulin (INS) (S = 5% demineralized water) was subjected to tryptic proteolysis (E/S 1/50; pH 5; 37 degrees C; 24 h). HPLC-as well as amino acid-and sequence analytical have shown that heptapeptide INS 23-29 (Gly-Phe-Phe-Tyr-Thr-Pro-Lys) liberated by way hydrolysis is linked via transpeptidation or condensation form a dimer which...
Abstract Immunocytokines (IC) leverage orthogonal mechanisms of action in one molecule to induce potent antitumor immune responses. PD-1-targeting ICs are particular interest since they harbor the multifunctional ability selectively target antigen-experienced PD-1+ CD8+ T cells enriched tumor microenvironment (TME), release them from PD-(L)1 pathway inhibition, be retained within TME, and simultaneously deliver cytokine receptor stimulation same cell cis (cis-signaling). Interleukin (IL-18)...