A5066305023- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- Lung Cancer Treatments and Mutations
- Cancer Treatment and Pharmacology
- Cancer Immunotherapy and Biomarkers
- Hematopoietic Stem Cell Transplantation
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Hematological disorders and diagnostics
- Mesenchymal stem cell research
- Nanoplatforms for cancer theranostics
- Cancer Cells and Metastasis
- Immune Cell Function and Interaction
- Radiopharmaceutical Chemistry and Applications
- CRISPR and Genetic Engineering
- Chemokine receptors and signaling
- Single-cell and spatial transcriptomics
- Monoclonal and Polyclonal Antibodies Research
- Cell Image Analysis Techniques
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Diabetic Foot Ulcer Assessment and Management
Roche (Switzerland)
2020-2025
ETH Zurich
2015-2023
Board of the Swiss Federal Institutes of Technology
2018-2021
RWTH Aachen University
2015
Circulating tumor cells (CTCs) are shed from solid cancers in the form of single or clustered cells, and latter display an extraordinary ability to initiate metastasis. Yet, biological phenomena that trigger shedding CTC clusters a primary cancerous lesion poorly understood. Here, when dynamically labeling breast cancer along progression, we observe majority undergoing hypoxia, while CTCs largely normoxic. Strikingly, find vascular endothelial growth factor (VEGF) targeting leads shrinkage,...
Expansion and differentiation of antigen-experienced PD-1+TCF-1+ stem-like CD8+ T cells into effector is critical for the success immunotherapies based on PD-1 blockade1-4. Hashimoto et al. have shown that, in chronic infections, administration cytokine interleukin (IL)-2 triggers an alternative path towards a distinct population 'better effector' similar to those generated acute infection5. IL-2 binding receptor α-chain (CD25) was essential triggering this expanding better effectors with...
Significance The development of an in vitro human bone marrow (BM) tissue appears essential to compile information on hematopoiesis. Conventional systems fail at both capturing the complexity niche while allowing maintenance functional hematopoietic stem cells (HSCs). Here, we report a 3D analogue perfusion-based bioreactor system, partially recapitulating structural, compositional, and organizational features native osteoblastic environment. engineered supports some progenitor cell (HSPC)...
Effective T-cell responses not only require the engagement of receptors (TCRs; "signal 1"), but also availability costimulatory signals ("signal 2"). bispecific antibodies (TCBs) deliver a robust signal 1 by engaging TCR signaling component CD3ε, while simultaneously binding to tumor antigens. The CD20-TCB glofitamab redirects T cells CD20-expressing malignant B cells. Although exhibits strong single-agent efficacy, adding may enhance depth and durability T-cell-mediated cell killing. We...
Abstract Purpose: CD40 agonists hold great promise for cancer immunotherapy (CIT) as they enhance dendritic cell (DC) activation and concomitant tumor-specific T-cell priming. However, the broad expression of accounts sink side effects, hampering efficacy anti-CD40 antibodies. We hypothesized that these limitations can be overcome by selectively targeting agonism to tumor. Therefore, we developed a bispecific FAP-CD40 antibody, which induces stimulation solely in presence fibroblast protein...
Abstract Therapies targeting the activation and recruitment of immune cells such as T or DCs to tumor microenvironment (TME) are considered highly promising approaches improve anti-tumor responses. Here, we evaluated synergistic efficacy PD1-IL2v in combination with FAP-CD40 syngeneic notoriously difficult treat KPC-4662 model. drives expansion stem-like CD8 their differentiation into effector cells, while FAP-CD40, a targeted CD40 agonist antibody, triggers DCs. Our aim was uncover spatial...
Abstract Cancer Immunotherapies (CITs) have shown unprecedented results in improving tumor control. However, many patients are still refractory to treatment. A deeper understanding of CIT-drugs mode action (MoA) may help improve therapeutic approaches reach better anti-tumor response. To this end, we developed a skinfold chamber model humanized mice that allows, by multi-photon intra-vital microscopy, the vivo study microenvironment. Analysis at single cell level upon treatment with...
Lung-resident immune cells, spanning both innate and adaptive compartments, preserve the integrity of respiratory barrier, but become pathogenic if dysregulated1. Current in vitro organoid models aim to replicate interactions between alveolar epithelium cells have not yet incorporated lung-specific critical for tissue residency2. Here we address this shortcoming by describing human lung immuno-organoids (LIO) that contain an autologous tissue-resident lymphoid compartment, primarily composed...
Tumors are populated by a multitude of immune cell types with varied phenotypic and functional properties, which can either promote or inhibit anti-tumor responses. Appropriate localization function these cells within tumors is critical for protective immunity, CD8 T infiltration being biomarker disease outcome therapeutic efficacy. Recent multiplexed imaging approaches have revealed highly complex patterns subsets the generation distinct tumor microenvironments (TMEs), vary among cancer...
Contribution of synergistic muscles toward specific movements over multi joint systems may change with varying position distal or proximal joints. Purpose this study is to reveal the relationship muscular coordination brachioradialis and biceps brachii during elbow flexion respect hand biomechanical advantages disadvantages brachii. A group 16 healthy subjects has been advised perform 20 repetitions single in different positions (pronated, neutral, supinated). With a speed 20°/s,...
Intestinal epithelial cell (IEC) NF-κB signaling regulates the balance between mucosal homeostasis and inflammation. It is not fully understood which signals tune this how bacterial exposure elicits process. Pure LPS induces activation in vivo. However, we found that mice, IECs do respond directly to LPS. Instead, tissue-resident lamina propria intercrypt macrophages sense via TLR4 rapidly secrete TNF elicit their immediate neighborhood. This response pattern relevant also during oral...
Abstract Blood-borne metastasis of breast cancer involves a series tightly regulated sequential steps, including the growth primary tumor lesion, intravasation circulating cells (CTC), and adaptation in various distant metastatic sites. The genes orchestrating each these steps are poorly understood physiologically relevant contexts, owing to rarity experimental models that faithfully recapitulate biology, kinetics, tropism human cancer. Here, we conducted an vivo loss-of-function CRISPR...
C-X-C motif chemokine ligand 12 (CXCL12; aka SDF1α) is a major regulator of number cellular systems, including hematopoiesis, where it influences hematopoietic cell trafficking, proliferation, and survival during homeostasis upon stress disease. A variety constitutive, temporal, ubiquitous, cell-specific loss-of-function models have documented the functional consequences on hematopoiesis deletion Cxcl12. Here, in contrast to experiments, we implemented gain-of-function approach by generating...
The generation of humanized ectopic ossicles (hOss) in mice has been proposed as an advanced translational and fundamental model to study the human hematopoietic system. approach relies on presence bone marrow-derived mesenchymal stromal cells (hMSCs) supporting engraftment transplanted stem progenitor (HSPCs). However, functional distribution hMSCs within microenvironment remains be investigated. Here, we combined genetic tools quantitative confocal microscopy engineer subsequently analyze...
The transcription factor (TF) GATA2 plays a key role in organ development and cell fate control the central nervous, urogenital, respiratory, reproductive systems, primitive definitive hematopoiesis. Here, we generate knockin protein reporter mouse line expressing GATA2VENUS fusion from endogenous Gata2 genomic locus, with correct expression localization of different organs. is heterogeneous hematopoietic stem progenitor populations (HSPCs), identifies functionally distinct subsets, suggests...