A5055289181- Systemic Lupus Erythematosus Research
- Organ and Tissue Transplantation Research
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- Organ Donation and Transplantation
- Viral-associated cancers and disorders
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- SARS-CoV-2 detection and testing
- COVID-19 Clinical Research Studies
- Lymphoma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Tissue Engineering and Regenerative Medicine
- Transplantation: Methods and Outcomes
- Erythrocyte Function and Pathophysiology
- CNS Lymphoma Diagnosis and Treatment
- Xenotransplantation and immune response
- Angiogenesis and VEGF in Cancer
- Respiratory viral infections research
- Mesenchymal stem cell research
- Vasculitis and related conditions
- Immunodeficiency and Autoimmune Disorders
- Pregnancy and preeclampsia studies
University of Bern
2016-2025
University Hospital of Bern
2016-2025
Federal Department of Home Affairs
2020-2024
Institute of Virology of the Slovak Academy of Sciences
2021-2023
German Rheumatism Research Centre
2011-2020
HES-SO University of Applied Sciences and Arts Western Switzerland
2019-2020
Weatherford College
2019
Charité - Universitätsmedizin Berlin
2012-2018
Humboldt-Universität zu Berlin
2018
Freie Universität Berlin
2018
Objectives To investigate whether bortezomib, a proteasome inhibitor approved for treatment of multiple myeloma, induces clinically relevant plasma cell (PC) depletion in patients with active, refractory systemic lupus erythematosus (SLE). Methods Twelve received median two (range 1–4) 21-day cycles intravenous bortezomib (1.3 mg/m 2 ) the coadministration dexamethasone (20 mg) active SLE. Disease activity was assessed using SLEDAI-2K score. Serum concentrations anti–double-stranded DNA...
Abstract Emerging variants of concern (VOCs) are driving the COVID-19 pandemic 1,2 . Experimental assessments replication and transmission major VOCs progenitors needed to understand mechanisms 3 Here we show that spike protein (S) from Alpha (also known as B.1.1.7) Beta (B.1.351) had a greater affinity towards human angiotensin-converting enzyme 2 (ACE2) receptor than progenitor variant S(D614G) in vitro. Progenitor virus expressing (wt-S 614G ) showed similar kinetics nasal airway...
Abstract Variant of concern (VOC) Omicron-BA.1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization advanced primary cell culture systems animal models are urgently needed. Here, we characterize recombinant spike gene mutants comparison with VOC Delta well-differentiated human nasal bronchial epithelial cells vitro, followed by vivo fitness hamsters, ferrets hACE2-expressing mice, immunized hACE2-mice. We demonstrate a spike-mediated...
Abstract Immunostimulatory properties of defensins on DC promote maturation and proinflammatory response. Defensins are endogenous defense peptides with well-defined antimicrobial activity against a broad spectrum pathogens including bacteria, fungi, viruses, parasites. Several lines evidence suggest that might also contribute to the regulation host innate adaptive immunity, but their immunomodulatory functions still poorly understood. Herein, we studied impact human multiple DCs, which...
Introduction: Human ear reconstruction is recognized as the emblematic enterprise in tissue engineering. Up to now, it has failed reach human applications requiring appropriate complexity along with an accessible vascular tree. We hereby propose a new method process auricles order provide poorly immunogenic, complex and vascularized graft scaffold. Methods: 12 ears their pedicles were procured. Perfusion-decellularization was applied using SDS/polar solvent protocol. Cell antigen removal...
Abstract During the evolution of SARS-CoV-2 in humans a D614G substitution spike (S) protein emerged and became predominant circulating variant (S-614G) COVID-19 pandemic 1 . However, whether increasing prevalence S-614G represents fitness advantage that improves replication and/or transmission or is merely due to founder effects remains elusive. Here, we generated isogenic variants demonstrate has (i) enhanced binding human ACE2, (ii) increased primary bronchial nasal airway epithelial...
The persistence of long-lived memory plasma cells in the bone marrow depends on survival factors available marrow, which are provided niches organized by stromal cells. Using an ex vivo system we supply known signals, direct cell contact to cells, and soluble cytokine a proliferation-inducing ligand (APRIL), have elucidated critical signaling pathways required for Integrin-mediated with activates phosphatidylinositol 3-kinase (PI3K) pathway, leading inactivation Forkhead-Box-Protein O1/3...
Approved vaccines are effective against severe COVID-19, but broader immunity is needed new variants and transmission. Therefore, we developed genome-modified live-attenuated (LAV) by recoding the SARS-CoV-2 genome, including 'one-to-stop' (OTS) codons, disabling Nsp1 translational repression removing ORF6, 7ab 8 to boost host immune responses, as well spike polybasic cleavage site optimize safety profile. The resulting OTS-modified LAVs, designated OTS-206 OTS-228, genetically stable can be...
Tyrosine phosphorylation of signaling molecules that mediate B cell activation in response to various stimuli is tightly regulated by protein tyrosine phosphatases (PTPs). PTP1B a ubiquitously expressed phosphatase with well-characterized functions metabolic pathways. We show here negatively regulates CD40, activating factor receptor (BAFF-R), and TLR4 cells. Specifically, counteracts p38 mitogen-activated kinase (MAPK) directly dephosphorylating Tyr182 this kinase. Mice cell–specific...
Abstract Antibody‐secreting cells (ASCs), including short‐lived plasmablasts and long‐lived memory plasma (LLPCs), contribute to autoimmune pathology. ASCs, particularly LLPCs, refractory conventional immunosuppressive drugs pose a major therapeutic challenge. Since stromal expressing C‐X‐C motif chemokine‐12 (CXCL12) organize survival niches for LLPCs in the bone marrow, we investigated effects of CXCL12 its ligand CXCR4 (C‐X‐C chemokine receptor 4) on ASCs lupus mice (NZB/W). Fewer...
Studies on severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have highlighted the crucial role of host proteases for viral replication and immune response. The serine furin TMPRSS2 lysosomal cysteine facilitate entry by limited proteolytic processing spike (S) protein. While neutrophils are recruited to lungs during COVID-19 pneumonia, little is known about neutrophil (NSPs) cathepsin G (CatG), elastase (NE), proteinase 3 (PR3) SARS-CoV-2 replication. Furthermore, current...
Long-lived plasma cells (LLPCs) are an unmet therapeutic challenge, and developing strategies for their targeting is emerging goal of autoantibody-mediated diseases such as systemic lupus erythematosus (SLE). It was previously shown that can be depleted by agents bortezomib (Bz) or blocking LFA-1 VLA-4 integrins. However, they regenerate quickly after depletion due to B cell hyperactivity in autoimmune conditions. Therefore, we compared different therapies the elimination LLPCs combined with...
During the last decade, face allotransplantation has been shown to be a revolutionary reconstructive procedure for severe disfigurements. However, offer patients remains limited due lifelong immunosuppression. To move forward in field, new pathway tissue engineering is proposed.Our previously reported technique of matrix production porcine auricular subunit graft translated human model.5 partial and 1 total grafts were procured from fresh cadavers. After arterial cannulation, specimens...
Routine application of vascularized composite allotransplantation is hampered by immunosuppression-related health comorbidities. To mitigate these, we developed an inflammation-responsive hydrogel for local immunosuppression. Here, report on its long-term effect graft survival, immunological, and toxicological impact.Brown Norway-to-Lewis rat hindlimb transplantations were treated either systemically with daily injections 1 mg/kg tacrolimus (TAC) or subcutaneous intragraft containing 7 mg...
The cellular reservoirs of Kaposi's sarcoma-associated herpesvirus (KSHV) and the exact nature putative KSHV-infected circulating precursor spindle cells sarcoma (KS) still remain poorly defined. Because KS are thought to be endothelial origin, because mature do not sustain persistent KSHV-infection, our attention was focalized on hematopoietic precursors able differentiate into lineage.Late progenitor (late-EPCs) were cultured from peripheral blood mononuclear 16 patients with classic KS....
The pathophysiology of chronic heart failure (CHF) involves multiple hystologic and molecular alterations. To determine the effects physical training on circulating endothelial progenitor cells (EPCs), angiogenesis (angiogenin, angiopoietin-1 -2, VEGF, Tie-2, SDF-1α) inflammation (IL-6, CRP), we compared data obtained from 11 CHF pts before after 3 months aerobic exercise training, to those 10 non trained (CHF-C group, age 64 + 2 years, NYHA 2). At end study, EPCs count AP-2 serum levels...
Vascularized composite allotransplantation is successful in reconstruction of major defects the upper extremity and face. Both rejection vascular damage seriously endanger outcome. The role adipose-derived stromal cells (ASCs) suppressing acute allotransplants their short-term protective effects on vessels remains widely unexplored. Systemic local donor-derived ASCs (CD45-CD29+CD90+) versus FK-506 administration was evaluated for reversal alterations fully mismatched rat hind-limb...
Abstract The IL‐1 family member IL‐36α has proinflammatory and pathogenic properties in psoriasis. binds to the IL‐36 receptor leading nuclear factor kappa B/mitogen activated protein kinase mediated cytokine release. IL‐36R antagonist prevents recruitment of accessory therefore IL‐36‐dependent cell activation. In inflamed human tissue, we previously could show that resident B cells plasma (PC) express IL‐36α. Further, fibroblast‐like synoviocytes (FLS) produced cytokines upon...