A5041692254- Single-cell and spatial transcriptomics
- Organ Transplantation Techniques and Outcomes
- Blood Coagulation and Thrombosis Mechanisms
- Barrier Structure and Function Studies
- Transplantation: Methods and Outcomes
- Angiogenesis and VEGF in Cancer
- Cardiac Ischemia and Reperfusion
- Lymphatic System and Diseases
- Cancer Cells and Metastasis
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cardiac and Coronary Surgery Techniques
- Atherosclerosis and Cardiovascular Diseases
- Zebrafish Biomedical Research Applications
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Cardiomyopathy and Myosin Studies
- Caveolin-1 and cellular processes
- Complement system in diseases
- Neuropeptides and Animal Physiology
- Xenotransplantation and immune response
- Acute Kidney Injury Research
- Adenosine and Purinergic Signaling
- Adipose Tissue and Metabolism
- Hippo pathway signaling and YAP/TAZ
Uppsala University
2014-2022
Science for Life Laboratory
2021-2022
Stanford University
2020-2021
Palo Alto University
2021
Palo Alto Veterans Institute for Research
2020
VA Palo Alto Health Care System
2020
Rationale: Pericytes are capillary mural cells playing a role in stabilizing newly formed blood vessels during development and tissue repair. Loss of pericytes has been described several brain disorders, genetically induced pericyte deficiency the leads to increased macromolecular leakage across blood-brain barrier (BBB). However, molecular details endothelial response remain elusive. Objective: To map transcriptional changes resulting from lack contact at single-cell level correlate them...
Single-cell transcriptomics promises to revolutionize our understanding of the vasculature. Emerging computational methods applied high dimensional single cell data allow integration results between samples and species, illuminate diversity underlying developmental architectural organization populations. Here, we illustrate these in analysis mouse lymph node (LN) lymphatic endothelial cells (LEC) at resolution. Clustering identifies five well-delineated subsets, including two medullary sinus...
Abstract Blood vascular endothelial cells (BECs) control the immune response by regulating blood flow and cell recruitment in lymphoid tissues. However, diversity of BEC their origins during angiogenesis remain unclear. Here we profile transcriptomes from peripheral lymph nodes map phenotypes to vasculature. We identify multiple subsets, including a medullary venous population whose gene signature predicts selective role myeloid (vs lymphocyte) medulla, confirmed videomicroscopy. define five...
Dysfunctional and leaky blood vessels resulting from disruption of the endothelial cell (EC) barrier accompanies numerous diseases. The EC is established through tight adherens junctions. However, expression pattern precise contribution different junctional proteins to poorly understood. Here, we focus on organs with continuous endothelium identify structural functional in vivo characteristics barrier. Assembly multiple single-cell RNAseq datasets into a single integrated database revealed...
Vascular endothelial (VE)-cadherin in adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated diseases such as cancer retinopathies. Inhibitors Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin phosphorylation prevent excessive leakage, edema high interstitial pressure. Here we show that Src-related Yes kinase, rather than Src, localized at cell (EC) where it becomes activated a flow-dependent manner....
PALMD (palmdelphin) belongs to the family of paralemmin proteins implicated in cytoskeletal regulation. Single nucleotide polymorphisms locus that result reduced expression are strong risk factors for development calcific aortic valve stenosis and predict severity disease.Immunodetection public database screening showed dominant endothelial cells (ECs) brain cardiovascular tissues including valves. Mass spectrometry, coimmunoprecipitation, immunofluorescent staining allowed identification...
Abstract Ischemia reperfusion injury is one of the major complications responsible for delayed graft function in kidney transplantation. Applications to reduce are essential due widespread use kidneys from deceased organ donors where risk especially prominent. We have recently shown that coating inflamed or damaged endothelial cells with a unique heparin conjugate reduces thrombosis and leukocyte recruitment. In this study we evaluated binding capacity cultured human cells, brain-dead...
Ischaemia-reperfusion injury (IRI) poses a major challenge in many thrombotic conditions and whole organ transplantation. Activation of the endothelial cells shedding protective vascular glycocalyx during IRI increase risk innate immune activation, cell infiltration severe thrombus formation, promoting damage to tissue. Here, we present novel one-step strategy protect vasculature by immobilisation unique multi-arm heparin conjugate endothelium. Applying new vitro blood chamber model, was...
Background Previously, we have been able to demonstrate the possibility of coating inner surface renal arteries in porcine kidneys with a heparin conjugate during hypothermic machine perfusion (HMP). The purpose this study was assess efficacy treatment reducing early ischemia-reperfusion injury. Method Brain death induced male landrace pigs by stepwise volume expansion an epidural balloon catheter until negative cerebral pressure (CPP) obtained. Both (matched pairs; n = 6 + 6) were preserved...
The impact of complement activation and its possible relation to cytokine responses during malaria pathology was investigated in plasma samples from patients with confirmed Plasmodium falciparum human whole-blood specimens stimulated malaria-relevant agents ex vivo. Complement significantly activated the cohort, compared healthy controls, positively correlated disease severity certain cytokines, particular interleukin 8 (IL-8)/CXCL8. This vivo–stimulated blood specimens, which inhibition...
Development of blood-forming (hemogenic) endothelial cells that give rise to hematopoietic stem and progenitor (HSPCs) is critical during embryogenesis generate the embryonic postnatal system. We previously demonstrated specification murine hemogenic promoted by retinoic acid (RA) signaling requires downstream cell cycle control. Whether this mechanism conserved in human unknown. Here, we present a protocol derive primordial from promote their toward cells. Furthermore, demonstrate RA...
The majority of all known diseases are accompanied by disorders the cardiovascular system. Studies into complexity interacting pathways activated during pathologies are, however, limited lack robust and physiologically relevant methods. In order to model pathological vascular events we have developed an in vitro assay for studying interaction between endothelium whole blood. consists primary human endothelial cells, which placed contact with method utilizes native blood no or very little...
Abstract Single-cell transcriptomics promises to revolutionize our understanding of the vasculature. Emerging computational methods applied high dimensional single cell data allow integration results between samples and species, illuminate diversity underlying developmental architectural organization populations. Here, we illustrate these in analysis mouse lymph node (LN) lymphatic endothelial cells (LEC) at resolution. Clustering identifies five well-delineated subsets, including two...
Abstract Corline Heparin Conjugate (CHC), a compound of multiple unfractionated heparin chains, coats cells with glycocalyx-like layer and may inhibit (xeno)transplant-associated activation the plasma cascade systems. Here, we investigated use CHC to protect WT genetically modified (GTKO.hCD46.hTBM) pig aortic endothelial (PAEC) in two pig-to-human vitro xenotransplantation settings. Model 1: incubation untreated or hTNFα-treated PAEC 10% human induced complement C3b/c C5b-9 deposition,...
Abstract Blood vascular endothelial cells (BECs) control the immune response by regulating cell recruitment, metabolite exchange and blood flow in lymphoid tissues. However, diversity of BEC their origins during angiogenesis remain poorly understood. Here we profile transcriptomes from mouse peripheral lymph nodes map key phenotypes to vasculature. Our analysis identifies multiple novel subsets including a venous population whose gene signature predicts an unexpectedly selective role myeloid...
The risk for adverse immune-mediated reactions, associated with the administration of certain immunotherapeutic agents, should be mitigated early. Infusion reactions to monoclonal antibodies and other biopharmaceuticals, known as cytokine release syndrome, can arise from cytokines via drug target cell, well recruitment immune effector cells. While several in vitro assays have been proposed up date, many them lack important blood components, required this response occur. endothelial cell...
The majority of all known diseases are accompanied by disorders the cardiovascular system. Studies into complexity interacting pathways activated during pathologies are, however, limited lack robust and physiologically relevant methods. In order to model pathological vascular events we have developed an in vitro assay for studying interaction between endothelium whole blood. consists primary human endothelial cells, which placed contact with method utilizes native blood no or very little...