- Mass Spectrometry Techniques and Applications
- Chemical synthesis and alkaloids
- Prostate Cancer Treatment and Research
- Trace Elements in Health
- Microbial Natural Products and Biosynthesis
- Immunotherapy and Immune Responses
- Molecular Biology Techniques and Applications
- Endoplasmic Reticulum Stress and Disease
- Advanced Proteomics Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Cancer therapeutics and mechanisms
- Immune cells in cancer
- Toxin Mechanisms and Immunotoxins
- Biochemical and Molecular Research
- Cancer, Lipids, and Metabolism
- interferon and immune responses
- Chemokine receptors and signaling
- Cancer Immunotherapy and Biomarkers
- Polyamine Metabolism and Applications
- Nuclear Physics and Applications
- Fungal Biology and Applications
- Cellular transport and secretion
- Heat shock proteins research
- Neurogenesis and neuroplasticity mechanisms
- Prostate Cancer Diagnosis and Treatment
Norwegian University of Science and Technology
2019-2025
St Olav's University Hospital
2024-2025
NTNU Samfunnsforskning
2022
Kiel University
2014-2018
Clinical Research Center Kiel
2018
Abstract Background Prostate cancer tissues are inherently heterogeneous, which presents a challenge for metabolic profiling using traditional bulk analysis methods that produce an averaged profile. The aim of this study was therefore to spatially detect metabolites and lipids on prostate tissue sections by mass spectrometry imaging (MSI), method facilitates molecular heterogeneous sections, can subsequently be related the histology same section. Methods Here, we simultaneously obtained...
Abstract Background Truly understanding the cancer biology of heterogeneous tumors in precision medicine requires capturing complexities multiple omics levels and spatial heterogeneity tissue. Techniques like mass spectrometry imaging (MSI) transcriptomics (ST) achieve this by spatially detecting metabolites RNA but are often applied to serial sections. To fully leverage advantage such multi-omics data, individual measurements need be integrated into 1 dataset. Results We present Multi-Omics...
Abstract Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated mechanisms through which cells escape treatment, but their relation toward tumor microenvironment (TME) remains elusive. Here we present comprehensive landscape of prostate TME at multiple points in standard timeline employing single-cell RNA-sequencing spatial transcriptomics data from 120 patients. We identify club-like as key epithelial...
MALDI MS imaging (MSI) is a powerful analytical tool for spatial peptide detection in heterogeneous tissues. Proper sample preparation crucial to achieve high quality, reproducible measurements. Here we developed an optimized protocol spatially resolved proteolytic with time-of-flight MSI of fresh frozen prostate tissue sections. The parameters tested included four different washes, methods protein denaturation, trypsin digestion (different densities, sprayers, and incubation times), five...
Levels of zinc, along with its mechanistically related metabolites citrate and aspartate, are widely reported as reduced in prostate cancer compared to healthy tissue therefore pointed out potential biomarkers. Previously, it has only been possible analyze zinc by separate detection methods. Through matrix-assisted laser desorption/ionization mass spectrometry imaging (MSI), we were for the first time able demonstrate, two different sample sets (n = 45 n 4), simultaneous spatial form ZnCl3–,...
Abstract To truly understand the cancer biology of heterogenous tumors in context precision medicine, it is crucial to use analytical methodology capable capturing complexities multiple omics levels, as well spatial heterogeneity tissue. Different molecular imaging techniques, such mass spectrometry (MSI) and transcriptomics (ST) achieve this goal by spatially detecting metabolites mRNA, respectively. take full advantage multi-omics data, individual measurements need be integrated into one...
Prostate tumor heterogeneity is a major obstacle when studying the biological mechanisms of molecular markers. Increased gene expression levels secreted frizzled-related protein 4 (SFRP4) biomarker in aggressive prostate cancer. To understand how SFRP4 relates to cancer we performed comprehensive spatial and multiomics analysis same tissue samples. The experimental workflow included transcriptomics, bulk proteomics, DNA methylomics staining. mRNA was predominantly located stroma, produced by...
Background: Biobanking of prostate cancer tissue is crucial for advancing biomarker-guided precision medicine. However, there no standardized optimal protocol biobanking prostatectomy specimens. This study aims to compare the representativeness and sustainability two protocols-"Punch" "Slice"-currently used in Norway. Methods: Fresh frozen from 40 radical specimens was biobanked using both Punch Slice protocols. Following macroscopic evaluation, a 2 mm thick transverse slice (Slice protocol)...
The transmembrane chemokines CX3CL1/fractalkine and CXCL16 are widely expressed in different types of tumors, often without an appropriate expression their classical receptors. We observed that receptor-negative cancer cells could be stimulated by the soluble chemokines. Searching for alternative receptors we detected all expressing or transfected with chemokine ligands bound high affinity responded phosphorylation intracellular kinases, enhanced proliferation anti-apoptosis. This activity...
Abstract The highly conserved bacterial homospermidine synthase (HSS) is a key enzyme of the polyamine metabolism many proteobacteria including pathogenic strains such as Legionella pneumophila and Pseudomonas aeruginosa ; unique usage NAD(H) prosthetic group common feature HSS, eukaryotic HSS deoxyhypusine (DHS). structure does not possess lysine residue in active center thus form an enzyme-substrate Schiff base intermediate observed for DHS. In contrast to DHS site formed by interface two...
Endoplasmic reticulum (ER)-resident proteins with a C-terminal KDEL ERretention sequence are captured in the Golgi apparatus by receptors (KDELRs). The binding of such to these induces their retrograde transport. Nevertheless, some proteins, as Protein Disulfide Isomerases (PDIs), found at cell surface. PDIs target disulfide bridges extracellular domains integrins or A Disintegrin And Metalloprotease 17 (ADAM17) leading changes structure and function molecules. Integrins become activated...
// Sebastian Krossa 1 , Anne Dorothée Schmitt 2 Kirsten Hattermann 3 Jürgen Fritsch 4 Axel J. Scheidig Hubertus Maximilian Mehdorn Janka Held-Feindt Institute of Zoology, Department Structural Biology, 24118 Kiel, Germany Neurosurgery, University Schleswig-Holstein Medical Center, 24105 Anatomy, Immunology, Correspondence to: Held-Feindt, e-mail: held-feindtj@nch.uni-kiel.de Keywords: akirin-2, twist-1, glioblastoma, chemoresistance Received: January 16, 2015 Accepted: April 06, Published:...
Abstract Understanding the molecular characteristics and changes of tumor microenvironment (TME) associated with aggressive prostate cancer (PCa) is essential for precise diagnosis treatment. We interrogated spatially resolved integrated transcriptomics metabolomics data to build strafiers discriminating patients aggressive, potentially relapsing, metastasizing PCa. report a relapse (RA) gene expression signature characterized by upregulated immune response related scoring high in cancer,...
<title>Abstract</title> Increased gene expression levels of secreted frizzled-related protein 4 (SFRP4) is a biomarker in aggressive prostate cancer. Prostate tumor heterogeneity major obstacle when studying the biological mechanisms molecular markers. To understand how <italic>SFRP4</italic> relates to cancer we performed comprehensive spatial and multiomics analysis same tissue samples. The experimental workflow included transcriptomics, bulk proteomics, DNA methylomics staining. mRNA was...
High secretion of the metabolites citrate and spermine is a unique hallmark for normal prostate epithelial cells, reduced in aggressive cancer. However, identity genes controlling this biological process mostly unknown. In study, we have created gene signature 150 connected to prostate. We computationally integrated metabolic measurements with multiple transcriptomics datasets from public domain, including 3826 tissue samples The accuracy validated by its enrichment compartments. highlights...
A rapid and cost-efficient tissue preparation protocol for laser ablation-inductively coupled plasma-mass spectrometry imaging (LA-ICP-MSI) has been developed within this study as an alternative to the current gold standard using fresh-frozen samples or other techniques such formalin fixation (FFix) formalin-fixed paraffin-embedding (FFPE). Samples were vacuum dried at room temperature (RT) stored in sealed containers storage shipping between collaborating parties. We compared our new...
A Disintegrin and Metalloprotease 17 (ADAM17) can cause the fast release of growth factors inflammatory mediators from cell surface. Its activity has to be turned on which occurs by various stimuli. The active form inactivated a structural change in its ectodomain, related pattern formed disulphide bridges. switch-off is executed protein disulfide isomerases (PDIs) that catalyze an isomerization two bridges thereby switch. We demonstrate integrity CGHC-motif within site PDIs indispensable....
The existence of endogenous neural progenitor cells (NPCs) in the adult spinal cord (sc) provides potential for tailored repair therapies after injury (SCI). This study investigates impact inflammatory mediators on properties NPC cultures derived from rats SCI. Infinite Horizon impactor was used to apply 200-kdyn thoracic sc lesions rats. Control groups received laminectomies equivalent regions. Thoracic segments were taken neurosphere cell cultures. Cell proliferation found be significantly...
Abstract Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated mechanisms through which cells escape treatment, but their relation toward tumor microenvironment (TME) remains elusive. Here we present comprehensive landscape of prostate TME at multiple points in standard timeline employing single-cell RNA-sequencing spatial transcriptomics data from 110 patients. We identify club-like as key epithelial...