A5091351703- Cellular Mechanics and Interactions
- Asthma and respiratory diseases
- Receptor Mechanisms and Signaling
- Cell Adhesion Molecules Research
- Mast cells and histamine
- Retinal Development and Disorders
- Advanced Fluorescence Microscopy Techniques
- Inflammatory mediators and NSAID effects
- Cellular transport and secretion
- IL-33, ST2, and ILC Pathways
- Protein Kinase Regulation and GTPase Signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Eicosanoids and Hypertension Pharmacology
- Microtubule and mitosis dynamics
- S100 Proteins and Annexins
- Cardiomyopathy and Myosin Studies
- Skin and Cellular Biology Research
- Neurobiology and Insect Physiology Research
- Immune Cell Function and Interaction
- Respiratory and Cough-Related Research
- Eosinophilic Esophagitis
- Food Allergy and Anaphylaxis Research
- Muscle Physiology and Disorders
- Blood disorders and treatments
- Urticaria and Related Conditions
Karolinska Institutet
2019-2024
Karolinska University Hospital
2022-2024
Babraham Institute
2014-2023
Uppsala University
2011
Stockholm University
2010-2011
Specific inflammatory pathways are indicated to contribute severe asthma, but their individual involvement in the development of airway hyperresponsiveness remains unexplored.This experimental study human small bronchi aimed provide insight into which type 2 and 17 cytokines cause smooth muscle.Explanted isolated from lung tissue muscle cells were treated for 1 day(s), respectively, with 100 ng/mL IL-4, IL-5, IL-13, or IL-17A, contractile responses, Ca2+ mobilization, receptor expression...
Highlights•Live quantification of RhoA activity during development and disease progression•Real-time visualization signaling in normal skin, osteocytes, neutrophils•Monitoring deregulation invasive mammary pancreatic cancers•Longitudinal vivo imaging inhibition using optical windowsSummaryThe small GTPase is involved a variety fundamental processes tissue. Spatiotemporal control thought to govern mechanosensing, growth, motility cells, while its associated with development. Here, we describe...
The small G protein family Rac has numerous regulators that integrate extracellular signals into tight spatiotemporal maps of its activity to promote specific cell morphologies and responses. Here, we have generated a mouse strain, Rac-FRET, which ubiquitously expresses the Raichu-Rac biosensor. It enables FRET imaging quantification in live tissues primary cells without affecting properties We assessed chemotaxing Rac-FRET neutrophils found enrichment leading-edge protrusions unexpected...
Abstract RAC1 activity is critical for intestinal homeostasis, and required hyperproliferation driven by loss of the tumour suppressor gene Apc in murine intestine. To avoid impact direct targeting upon we reasoned that indirect via RAC-GEFs might be effective. Transcriptional profiling deficient tissue identified Vav3 Tiam1 as key targets. Deletion these indicated while TIAM1 deficiency could suppress Apc- hyperproliferation, it had no tumourigenesis, VAV3 effect. Intriguingly, deletion...
Dysregulated T-cell activation is a hallmark of several autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS). The lymphocyte cytosolic protein 2 (LCP2), also known SLP-76, essential for the development T cells. Despite critical role LCP2 in need developing drugs that modify activation, no inhibitors have been developed. This can be explained by "undruggable" nature LCP2, lacking structure permissive to standard small molecule inhibitor modalities. Here, we...
Introduction Rac-GTPases and their Rac-GEF activators play important roles in neutrophil-mediated host defence. These proteins control the adhesion molecules cytoskeletal dynamics required for neutrophil recruitment to inflamed infected organs, effector responses that kill pathogens. Methods Here, we used live cell TIRF-FRET imaging neutrophils from Rac-FRET reporter mice with deficiencies Rac-GEFs Dock2, Tiam1 or Prex1/Vav1 evaluate if these activate spatiotemporally distinct pools of Rac,...
The major mast cell prostanoid PGD2 is targeted for therapy of asthma and other diseases, because the biological actions include bronchoconstriction, vasodilation regulation immune cells mediated by three different receptors. It not known if alternative to selectively inhibit biosynthesis affects release prostanoids in human cells.To determine biochemical consequences inhibition hematopoietic prostaglandin D synthase (hPGDS) cells.Four models, LAD2, cord blood derived (CBMC), peripheral...
Mast cells are critically involved in IgE-mediated diseases, e.g., allergies and asthma. Human mast heterogeneous, from different anatomical sites have been shown to respond differently certain stimuli drugs. The origin of the is therefore importance when setting up a model system, human lung highly relevant study context We set out optimize protocol activation cells. were extracted tissue obtained patients undergoing pulmonary resection by enzyme digestion mechanical disruption followed...
Rac GTPases are required for neutrophil adhesion and migration, the effector responses that kill pathogens. These Rac-dependent functions impaired when neutrophils lack activators of Rac, Rac-GEFs from Prex, Vav, Dock families. In this study, we demonstrate Tiam1 is also expressed in neutrophils, governing focal complexes, actin cytoskeletal dynamics, polarisation, a manner depending on integrin ligand to which cells adhere. dispensable generation reactive oxygen species but mediates...
<p>Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-Forster resonance energy transfer (FRET) biosensor mouse coupled in vivo photoswitching track intratumoral movement, we help guide treatment scheduling breast cancer setting impair metastatic progression. We uncover altered Rac1 activity at the center versus invasive border tumors...
<b>Background:</b> The major mast cell prostanoid PGD<sub>2</sub> is an interesting target for therapeutic intervention because of its influence on bronchoconstriction, vasodilation and eosinophilic recruitment. We investigated the biochemical impact inhibition biosynthesis in four human models. <b>Methods:</b> Mast cells (LAD2, cord blood derived (CBMC), peripheral (PBMC) lung (HLMC)) were activated by anti-IgE or ionophore A23187. Expression COX-1, COX-2 hematopoietic prostaglandin D...
<p>Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-Forster resonance energy transfer (FRET) biosensor mouse coupled in vivo photoswitching track intratumoral movement, we help guide treatment scheduling breast cancer setting impair metastatic progression. We uncover altered Rac1 activity at the center versus invasive border tumors...