A5038250336- Monoclonal and Polyclonal Antibodies Research
- Mast cells and histamine
- HER2/EGFR in Cancer Research
- Drug-Induced Adverse Reactions
- Protein purification and stability
- Liver Disease Diagnosis and Treatment
- Urticaria and Related Conditions
- Immune cells in cancer
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Chronic Lymphocytic Leukemia Research
- Cell Adhesion Molecules Research
- Advanced Biosensing Techniques and Applications
- Adipose Tissue and Metabolism
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Liver physiology and pathology
- Phagocytosis and Immune Regulation
- Trace Elements in Health
- Microtubule and mitosis dynamics
- Liver Diseases and Immunity
- Viral Infectious Diseases and Gene Expression in Insects
- interferon and immune responses
- Wnt/β-catenin signaling in development and cancer
- 3D Printing in Biomedical Research
Novartis Institutes for BioMedical Research
2012-2024
Novartis (Switzerland)
2011-2024
Humans lacking sclerostin display progressive bone overgrowth due to increased formation. Although it is well established that an osteocyte-secreted formation inhibitor, the underlying molecular mechanisms are not fully elucidated. We identified in tandem affinity purification proteomics screens LRP4 (low density lipoprotein-related protein 4) as a interaction partner. Biochemical assays with recombinant proteins confirmed direct. Interestingly, vitro overexpression and RNAi-mediated...
The extracellular serine protease inhibitor serpinE2 is overexpressed in breast cancer and has been shown to foster metastatic spread. Here, we investigated the hypothesis that creates tumor-promoting conditions tumor microenvironment (TME) by affecting matrix remodeling. Using two different models, show blocking serpinE2, either knock-down (KD) cells or response a binding antibody, decreases dissemination from primary tumors lungs. We demonstrate KD antibody treatment there are dramatic...
Purpose: Hypersensitivity reactions (HSRs) were observed in three patients dosed a phase I clinical trial treated with LOP628, KIT targeted antibody drug conjugate. Mast cell degranulation was implicated as the root cause for HSR. Underlying mechanism of this reported HSR investigated an aim to identifying potential mitigation strategies.Experimental Design: Biomarkers mast evaluated patient samples and human peripheral blood cell-derived (PBC-MC) cultures LOP628. Mitigation strategies...
ABSTRACT Resident and recruited macrophages control the development proliferation of liver. We have previously shown in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte promoted repair models acute hepatic injury mice. Here, we investigated impact CSF1-Fc on resolution advanced fibrosis liver regeneration, using non-resolving toxin-induced model chronic C57BL/6J Co-administration exposure to thioacetamide (TAA)...
Abstract Deficiency of adenosine deaminase 2 (DADA2) is a severe, congenital syndrome, which manifests with hematologic, immunologic and inflammatory pathologies. DADA2 caused by biallelic mutations in ADA2 , but the function ADA2, mechanistic link between deficiency severe phenotype remains unclear. Here, we show that monocyte-derived proteomes from patients are highly enriched interferon response proteins. Using immunohistochemistry detailed glycan analysis demonstrate post-translationally...
HLA-B27 and HLA-B57 are associated with autoimmunity long-term viral control protection against HIV HCV infection; however, their role in cancer immunity remains unknown. HLA class I molecules interact innate checkpoint receptors of the LILRA, LILRB KIR families present diverse sets immune cells. Here, we demonstrate that an open format (peptide free conformation) expression- stability-optimized HLA-B57-B2m-IgG4_Fc fusion protein (IOS-1002) binds to human leukocyte immunoglobulin-like...
Abstract Resident and recruited macrophages control the development proliferation of liver. We showed previously in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte promoted repair models acute hepatic injury mice. Here we investigated impact CSF1-Fc on resolution advanced fibrosis liver regeneration, utilizing non-resolving toxin-induced model chronic C57BL/6J Co-administration exposure to thioacetamide (TAA)...
Macrophages and their secreted effectors are known to regulate metabolic homeostasis in health disease. Here we explore the impact of expansion tissue macrophage populations mice using a long-acting form colony stimulating factor 1 (CSF1). Rapid reversible response CSF1 treatment led somatic hepatic growth, increased glucose uptake extensive mobilisation body fat. The was independent several endocrine regulators metabolism did not physiological fasting response. Analysis implantable...
<div>Abstract<p><b>Purpose:</b> Hypersensitivity reactions (HSRs) were observed in three patients dosed a phase I clinical trial treated with LOP628, KIT targeted antibody drug conjugate. Mast cell degranulation was implicated as the root cause for HSR. Underlying mechanism of this reported HSR investigated an aim to identifying potential mitigation strategies.</p><p><b>Experimental Design:</b> Biomarkers mast evaluated patient samples and...
<p>Unconjugated LOP628, LMJ729, activity in mast cell degranulation assays</p>
<p>Representative FACs staining of in vitro generated mast cells confirming maturation</p>
<p>Unconjugated LOP628, LMJ729, activity in mast cell degranulation assays</p>
<div>Abstract<p><b>Purpose:</b> Hypersensitivity reactions (HSRs) were observed in three patients dosed a phase I clinical trial treated with LOP628, KIT targeted antibody drug conjugate. Mast cell degranulation was implicated as the root cause for HSR. Underlying mechanism of this reported HSR investigated an aim to identifying potential mitigation strategies.</p><p><b>Experimental Design:</b> Biomarkers mast evaluated patient samples and...
<p>Representative FACs staining of in vitro generated mast cells confirming maturation</p>
<p>Confirmatory FACs binding of LMJ729 engineered Fc mutants</p>
<p>F(ab')2-LMJ729 degranulation assay of hIFNg-treated mast cells</p>
<p>Additional small molecule inhibition of LMJ729/LOP628-mediated degranulation</p>