A5068478683- Angiogenesis and VEGF in Cancer
- Cancer Cells and Metastasis
- Nuclear Receptors and Signaling
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Cancer, Hypoxia, and Metabolism
- Retinoids in leukemia and cellular processes
- Cytokine Signaling Pathways and Interactions
- Prostate Cancer Treatment and Research
- Cell Adhesion Molecules Research
- Lung Cancer Treatments and Mutations
- Protease and Inhibitor Mechanisms
- 3D Printing in Biomedical Research
- Kruppel-like factors research
- Advanced Fluorescence Microscopy Techniques
- Cancer Research and Treatments
- Fibroblast Growth Factor Research
- Mechanisms of cancer metastasis
- TGF-β signaling in diseases
- Chemokine receptors and signaling
- Bone health and treatments
- Lung Cancer Research Studies
- Glycosylation and Glycoproteins Research
- S100 Proteins and Annexins
- Biomarkers in Disease Mechanisms
Cornell University
2010-2023
University of Zurich
2016-2021
Hexagon (Switzerland)
2021
IBM Research - Zurich
2019
Life Science Zurich
2018
Kettering University
2015
Haukeland University Hospital
2013
Boston Children's Hospital
2013
University of Bergen
2013
College Medical Center
2013
CRISPR-Cas9 enables efficient sequence-specific mutagenesis for creating somatic or germline mutants of model organisms. Key constraints in vivo remain the expression and delivery active Cas9-sgRNA ribonucleoprotein complexes (RNPs) with minimal toxicity, variable efficiencies depending on targeting sequence, high mutation mosaicism. Here, we apply vitro assembled, fluorescent RNPs solubilizing salt solution to achieve maximal efficiency zebrafish embryos. MiSeq-based sequence analysis...
Abstract Tumors systemically initiate metastatic niches in distant target organs. These niches, composed of bone marrow–derived hematopoietic cells, provide permissive conditions for future metastases. However, the mechanisms by which these cells mediate outgrowth tumor are not completely known. Using mouse models spontaneous breast cancer, we show enhanced recruitment CD11b+Gr1+ myeloid progenitor premetastatic lungs. Gene expression profiling revealed that from lungs express versican, an...
Significance Lungs are highly susceptible to inflammation. However, molecular insights into how external inflammation enhances metastatic outgrowth in the lungs remain lacking. Clinically, approaches required block tumor secondary organs for effective treatment of cancers. We demonstrate a previously unidentified mechanism thrombospondin-1 (Tsp-1) regulation by inflammatory neutrophil proteases organ. Our findings suggest potential using protease inhibitors as antimetastatic therapies.
Abstract A holistic understanding of tissue and organ structure function requires the detection molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous up to 40 antigens transcripts using metal-tagged antibodies but has so far been restricted two-dimensional imaging. Here we report development 3D IMC for multiplexed analysis at single-cell resolution demonstrate utility technology by human breast cancer samples. The resulting...
Abstract Metastatic tumors have been shown to establish permissive microenvironments for metastases via recruitment of bone marrow–derived cells. Here, we show that metastasis-incompetent are also capable generating such microenvironments. However, in these situations, the otherwise prometastatic Gr1+ myeloid cells create a metastasis-refractory microenvironment induction thrombospondin-1 (Tsp-1) by tumor-secreted prosaposin. Bone marrow–specific genetic deletion Tsp-1 abolished inhibition...
Abstract Background There is strong evidence demonstrating that activation of epidermal growth factor receptors (EGFRs) leads to tumor growth, progression, invasion and metastasis. Erlotinib gefitinib, two EGFR-targeted agents, have been shown be relevant drugs for lung cancer treatment. Recent studies demonstrate lapatinib, a dual tyrosine kinase inhibitor EGFR HER-2 receptors, clinically effective against HER-2-overexpressing metastatic breast cancer. In this report, we investigated the...
Different isoforms of VEGF-A (mainly VEGF₁₂₁, VEGF₁₆₅ and VEGF189) have been shown to display particular angiogenic properties in the generation a functional tumor vasculature. Recently, novel class isoforms, designated as VEGF(xxx)b, generated through alternative splicing, described. Previous studies suggested that these may inhibit angiogenesis. In present work we produced recombinant VEGF₁₂₁/₁₆₅b proteins yeast Pichia pastoris constructed vectors overexpress assess their...
Mortality rates in lung cancer patients have not decreased significantly recent years, even with the implementation of new therapeutic regimens. One main problems is that a large proportion present local or distant metastasis at time diagnosis. The need for identification novel biomarkers and targets more effective management led us to investigate TMPRSS4, protease reported promote tumour growth metastasis. In all, 34 cell lines were used evaluate TMPRSS4 expression. Cell migration...
Abstract Tumor angiogenesis is essential for malignant growth and metastasis. Bone marrow (BM)–derived endothelial progenitor cells (EPC) contribute to angiogenesis-mediated tumor growth. EPC ablation can reduce growth; however, the lack of a marker that track EPCs from BM neovasculature has impeded progress in understanding molecular mechanisms underlying biology. Here, we report use transgenic mouse lentiviral models monitor BM-derived compartment stroma; this approach exploits selectivity...
Bone microenvironment and cell-cell interactions are crucial for the initiation development of metastasis. By means a pharmacologic approach, using multitargeted tyrosine kinase inhibitor sunitinib, we tested relevance platelet-derived growth factor receptor (PDGFR) axis in bone marrow (BM) stromal compartment lung cancer metastasis to bone. PDGFRβ was found be main target sunitinib expressed BM ST-2 MC3T3-E1 preosteoblastic cells. In contrast, no expression sunitinib-targeted receptors...
Imaging and image analysis advances are yielding increasingly complete complicated records of cellular events in tissues whole embryos. The ability to follow hundreds thousands cells at the individual level demands a spatio-temporal data infrastructure: tools assemble collate knowledge about development spatially manner analogous geographic information systems (GIS). Just as GIS indexes items or based on their 4D location Earth these would organize within Developmental processes highly...
Clinical morphological analysis of histopathology samples is an effective method in cancer diagnosis. Computational pathology methods can be employed to automate this analysis, providing improved objectivity and scalability. More specifically, computational techniques used segmenting glands, which essential factor Automatic delineation glands a challenging task considering large variability glandular morphology across tissues pathological subtypes. A deep learning based gland segmentation...
Abstract Mass cytometry facilitates high‐dimensional, quantitative, single‐cell analysis. The method for sample multiplexing in mass cytometry, called mass‐tag cellular barcoding (MCB), relies on the covalent reaction of bifunctional metal chelators with intracellular proteins. Here, we describe use osmium and ruthenium tetroxides (OsO 4 RuO ) that bind covalently fatty acids membranes aromatic amino Both OsO rapidly reacted allowed MCB live cells, crosslinked permeabilized cells. Given...
Abstract Imaging mass cytometry is a novel imaging modality that enables simultaneous antibody‐based detection of >40 epitopes and molecules in tissue sections at subcellular resolution by the use isotopically pure metal tags. Essential for any approach which antigen performed counterstaining, reveals overall structure tissue. Counterstaining necessary because antigens interest are often present only small subset cells, rest structures not visible. As most biological tissues nearly...
Vascular endothelial growth factor (VEGF) is a proangiogenic upregulated in many tumors. The alternative splicing of VEGF mRNA renders 3 major isoforms 121, 165 and 189 amino-acids humans (1 less amino-acid for each mouse isoform). We have designed isoform specific real time QRT-PCR assays to quantitate transcripts human normal malignant prostates. In the prostate, VEGF(165) was predominant (62.8% +/- 5.2%), followed by VEGF(121) (22.5% 6.3%) VEGF(189) (p < 0.001) (14.6% 2.1%). Prostate...
Radiotherapy (RT) is a common treatment for localised prostate cancer, but can cause important side effects. The therapeutic efficacy of RT be enhanced by pharmacological compounds that target specific pathways involved in cell survival. This would elicit similar response using lower doses and, turn, reducing study describes the antitumour activity novel Akt inhibitor 8-(1-Hydroxy-ethyl)-2-methoxy-3-(4-methoxy-benzyloxy)-benzo[c]chromen-6-one (Palomid 529 or P529) as well its ability to...
Abstract BACKGROUND Oxidative stress plays a role in prostate cancer (PrCa) initiation and development. Selenoprotein‐P (SepP; protein involved antioxidant defence) mRNA levels are down‐regulated PrCa. The main goal of our study was to assess whether SepP protects cells from reactive oxygen species (ROS) carcinogenesis. METHODS Modification ROS conditions C3(1)/Tag‐derived cell lines representing epithelial neoplasia (PIN) lesions (Pr‐111, with high expression); invasive tumors (Pr‐14, very...