Pablo J. Sáez

ORCID: 0000-0003-0521-9426
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About
Contact & Profiles
Research Areas
  • Cellular Mechanics and Interactions
  • Connexins and lens biology
  • Immunotherapy and Immune Responses
  • Cell Adhesion Molecules Research
  • Adenosine and Purinergic Signaling
  • Nicotinic Acetylcholine Receptors Study
  • T-cell and B-cell Immunology
  • Cellular transport and secretion
  • Heme Oxygenase-1 and Carbon Monoxide
  • 3D Printing in Biomedical Research
  • Immune Response and Inflammation
  • Calcium signaling and nucleotide metabolism
  • Neuroinflammation and Neurodegeneration Mechanisms
  • Cell Image Analysis Techniques
  • Biochemical effects in animals
  • Force Microscopy Techniques and Applications
  • Immune cells in cancer
  • Cancer Cells and Metastasis
  • Immune Cell Function and Interaction
  • Renal Diseases and Glomerulopathies
  • Lysosomal Storage Disorders Research
  • Single-cell and spatial transcriptomics
  • Neuroscience of respiration and sleep
  • Advanced Fluorescence Microscopy Techniques
  • Autophagy in Disease and Therapy

Universität Hamburg
2020-2025

University Medical Center Hamburg-Eppendorf
2020-2025

CRUK Lung Cancer Centre of Excellence
2024

Cancer Institute (WIA)
2024

Université Paris Sciences et Lettres
2016-2023

Institut Curie
2015-2023

Centre National de la Recherche Scientifique
2017-2023

Institut Pierre-Gilles de Gennes pour la Microfluidique
2017-2023

Inserm
2011-2020

Immunité et Cancer
2016-2019

Astrocytes have a role in maintaining normal neuronal functions, some of which depend on connexins, protein subunits gap junction channels and hemichannels. Under inflammatory conditions, microglia release cytokines, including interleukin-1β tumor necrosis factor-α, that reduce intercellular communication via junctions. Now, we demonstrate either conditioned medium harvested from activated or mixture these two cytokines enhances the cellular exchange with extracellular milieu Cx43 These...

10.1523/jneurosci.2042-07.2007 article EN cc-by-nc-sa Journal of Neuroscience 2007-12-12

The nucleus makes the rules Single cells continuously experience and react to mechanical challenges in three-dimensional tissues. Spatial constraints dense tissues, physical activity, injury all impose changes cell shape. How can measure shape deformations ensure correct tissue development homeostasis remains largely unknown (see Perspective by Shen Niethammer). Working independently, Venturini et al. Lomakin now show that act as an intracellular ruler cellular variations. nuclear envelope...

10.1126/science.aba2894 article EN Science 2020-10-16

The mechanisms involved in Alzheimer's disease are not completely understood and how glial cells contribute to this neurodegenerative remains be elucidated. Because inflammatory treatments products released from activated microglia increase hemichannel activity, we investigated whether amyloid-β peptide (Aβ) could regulate these channels affect neuronal viability. Microglia, astrocytes, or cultures as well acute hippocampal slices made GFAP-eGFP transgenic mice were treated with the active...

10.1523/jneurosci.6417-10.2011 article EN cc-by-nc-sa Journal of Neuroscience 2011-03-30

Abstract Despite decades of research, how mammalian cell size is controlled remains unclear because the difficulty directly measuring growth at single-cell level. Here we report direct measurements volumes over entire cycles on various lines and primary human cells. We find that, in a majority types, volume added across cycle shows little or no correlation to birth size, homeostatic behavior called “adder”. This involves modulation G1 S-G2 duration rate. The precise combination these...

10.1038/s41467-018-05393-0 article EN cc-by Nature Communications 2018-08-10

Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These can adapt to such deformation events using dedicated shape-sensing pathways. However, how sensing affects immune function is mostly unknown. Here, we identify a mechanism increases expression chemokine receptor CCR7 and guides dendritic migration from peripheral tissues lymph nodes at steady state. This relies on lipid...

10.1038/s41590-024-01856-3 article EN cc-by Nature Immunology 2024-06-04

Abstract The ventromedial hypothalamus is involved in regulating feeding and satiety behavior, its neurons interact with specialized ependymal‐glial cells, termed tanycytes. latter express glucose‐sensing proteins, including glucose transporter 2, glucokinase, ATP‐sensitive K + (K ATP ) channels, suggesting their involvement hypothalamic glucosensing. Here, the transduction mechanism glucose‐induced rise of intracellular free Ca 2+ concentration ([Ca ] i cultured β‐tanycytes was examined....

10.1002/glia.21246 article EN Glia 2011-10-10

Upon its release from injured cells, such as infected, transformed, inflamed, or necrotic extracellular adenosine-5'-triphosphate (ATP) acts a danger signal that recruits phagocytes, neutrophils, macrophages, and dendritic cells (DCs), to the site of injury. The sensing ATP occurs through purinergic (P2) receptors. We investigated cellular mechanisms linking signaling DC motility. found stimulated fast motility an autocrine loop, which was initiated by activation P2X7 receptors further...

10.1126/scisignal.aah7107 article EN Science Signaling 2017-11-21

Abstract Cell polarity is required for the functional specialization of many cell types including lymphocytes. A hallmark reorientation centrosome that allows repositioning organelles and vesicles in an asymmetric fashion. The mechanisms underlying polarization are not fully understood. Here we found resting lymphocytes, centrosome-associated Arp2/3 locally nucleates F-actin, which needed tethering to nucleus via LINC complex. Upon lymphocyte activation, partially depleted from as a result...

10.1038/ncomms10969 article EN cc-by Nature Communications 2016-03-18

MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from membranes to the plasma and/or mitochondria, toxin-induced resistance, and mitochondrial dysfunction. Down-regulation of Niemann-Pick C1 deficient cells decreased content, suggesting functions independently NPC1. However, role maintenance flow intracellular homeostasis remains unclear. We have previously described hepatic overexpression increases liver content induces damage....

10.1016/j.redox.2017.02.024 article EN cc-by-nc-nd Redox Biology 2017-03-02

Abstract An important channel of cell-to-cell communication is direct contact. The immune synapse a paradigmatic example such type interaction: it forms upon engagement antigen receptors in lymphocytes by antigen-presenting cells and allows the local exchange molecules information. Although mechanics has been shown to play an role this process, how forces organize impact on function unknown. We find that mechanical are spatio-temporally patterned at synapse: global pulsatile myosin II-driven...

10.1038/s41467-019-10751-7 article EN cc-by Nature Communications 2019-06-28

Expansion microscopy physically enlarges biological specimens to achieve nanoscale resolution using diffraction-limited systems1. However, optimal performance is usually reached laser-based systems (for example, confocal microscopy), restricting its broad applicability in clinical pathology, as most centres have access only light-emitting diode (LED)-based widefield systems. As a possible alternative, computational method for image enhancement, namely, super-resolution radial fluctuations...

10.1038/s41565-023-01328-z article EN cc-by Nature Nanotechnology 2023-04-01

The all-terrain motility of lymphocytes in tissues and tissue-like gels is best described as amoeboid motility. For motility, do not require specific biochemical or structural modifications to the surrounding extracellular matrix. Instead, they rely on changing shape steric interactions with microenvironment. However, exact mechanism remains elusive. Here, we report that septins participate T cells, enabling formation F-actin α-actinin-rich cortical rings at sites cell cortex-indenting...

10.1126/sciadv.adi1788 article EN cc-by-nc Science Advances 2024-01-03

Abstract Previously, we found that human dendritic cells (hDCs) pulsed with a melanoma cell lysate (MCL) and stimulated TNF-α (MCL/TNF) acquire mature phenotype in vitro are able to trigger tumor-specific immune responses when they used immunotherapy patients. In this study, describe MCL/TNF induces gap junction (GJ)-mediated intercellular communications promotes Ag transfer between ex vivo produced hDCs from also exhibit increased expression of the GJ-related protein connexin 43, which...

10.4049/jimmunol.178.11.6949 article EN The Journal of Immunology 2007-06-01

CKD (chronic kidney disease) has become a public health problem. The therapeutic approaches have been able to reduce proteinuria, but not successful in limiting disease progression. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of MSC (mesenchymal stem cells) on progression and expression molecular biomarkers effects. Adult male Sprague-Dawley rats subjected 5/6 NPX (nephrectomy) received single intravenous...

10.1042/cs20110108 article EN Clinical Science 2011-07-04

Therapeutic approaches for CKD (chronic kidney disease) have been able to reduce proteinuria, but not diminish the disease progression. We demonstrated beneficial effects by injection of BM (bone marrow)-derived MSCs (mesenchymal stem cells) from healthy donors in a rat model with CKD. However, it has recently reported that BM-MSCs derived uraemic patients failed confer functional protection similar model. This suggests autologous are suitable treatment In present study, we explored...

10.1042/cs20120644 article EN Clinical Science 2013-03-13

Upon infection, mature dendritic cells (mDCs) migrate from peripheral tissue to lymph nodes (LNs) activate T lymphocytes and initiate the adaptive immune response. This fast tightly regulated process is tuned by different microenvironmental factors, such as physical properties of tissue. Mechanistically, mDCs migration mostly relies on acto-myosin flow contractility that depend non-muscular Myosin IIA (MyoII) activity. However, specific contribution this molecular motor for navigation in...

10.3389/fimmu.2019.00747 article EN cc-by Frontiers in Immunology 2019-04-12

Death of murine T cells induced by extracellular ATP is mainly triggered activation purinergic P2X7 receptors (P2X7Rs). However, a link between P2X7Rs and pannexin1 (Panx1) channels, which are non-selective, has been recently demonstrated in other cell types. In this work, we characterized the expression cellular distribution pannexin family members (Panxs 1, 2 3) isolated cells. Panx1 was main member clearly detected both helper (CD4+) cytotoxic (CD8+) cells, whereas low levels Panx2 were...

10.4161/chan.28122 article EN Channels 2014-03-01

Satellite glial cells (SGCs) are the main glia in sensory ganglia. They surround neuronal bodies and form a cap that prevents formation of chemical or electrical synapses between neighboring neurons. SGCs have been suggested to establish bidirectional paracrine communication with However, molecular mechanism involved this cellular is unknown. In central nervous system (CNS), astrocytes present connexin43 (Cx43) hemichannels pannexin1 (Panx1) channels, opening these channels allows release...

10.3389/fncel.2014.00158 article EN cc-by Frontiers in Cellular Neuroscience 2014-06-20
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