Manuel A. Sánchez-García
A5010843495- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Respiratory Support and Mechanisms
- Hemoglobin structure and function
- High Altitude and Hypoxia
- Sepsis Diagnosis and Treatment
- COVID-19 Clinical Research Studies
- Metabolism and Genetic Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological Disease Mechanisms and Treatments
- MicroRNA in disease regulation
- Immune Response and Inflammation
- Alzheimer's disease research and treatments
- Neurogenesis and neuroplasticity mechanisms
- Biochemical Acid Research Studies
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Axon Guidance and Neuronal Signaling
- Barrier Structure and Function Studies
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Memory and Neural Mechanisms
- Diet and metabolism studies
- FOXO transcription factor regulation
- Angiogenesis and VEGF in Cancer
- Cancer Research and Treatments
University of Edinburgh
2020-2024
Centre for Inflammation Research
2020-2024
The Queen's Medical Research Institute
2020-2023
Queen's Medical Centre
2020-2022
Hospital Universitario Virgen del Rocío
2017-2021
Universidad de Sevilla
2017-2021
Instituto de Biomedicina de Sevilla
2017-2021
Neutrophils can function and survive in injured infected tissues, where oxygen metabolic substrates are limited. Using radioactive flux assays LC-MS tracing with U-13C glucose, glutamine, pyruvate, we observe that neutrophils require the generation of intracellular glycogen stores by gluconeogenesis glycogenesis for effective survival bacterial killing. These adaptations dynamic, net increases observed following LPS challenge or altitude-induced hypoxia. from patients chronic obstructive...
Rationale: COPD (Chronic Obstructive Pulmonary Disease) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in bioenergetics contribute impaired antioxidant responses pathogenesis has yet be fully delineated. Objectives: Through the study of alveolar (AM) peripheral monocyte-derived (MDM) macrophages, we sought establish if intrinsic defects core metabolic processes drive dysfunction redox imbalance. Methods: AM MDM...
Abstract Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, often neglected. In present study, we have shown that ARDS patients were hypoxemic monocytopenic within first 48 h ventilation. Monocytopenia was also observed in mouse models hypoxic lung injury, which hypoxemia drove suppression type I interferon signaling bone marrow....
Scientists found a new miRNA involved in macrophage responses, paving the way for an improved management of inflammatory diseases.
Background: Acute respiratory distress syndrome (ARDS) is a severe critical condition with high mortality that currently in focus given it associated caused by coronavirus disease 2019 (COVID-19). Neutrophils play key role the lung injury characteristic of non-COVID-19 ARDS and there also accumulating evidence neutrophil mediated patients who succumb to infection acute 2 (SARS-CoV-2). Methods: We undertook functional proteomic metabolomic survey circulating populations, comparing COVID-19...
<ns3:p><ns3:bold>Background: </ns3:bold>Acute respiratory distress syndrome (ARDS) is a severe critical condition with high mortality that currently in focus given it associated caused by coronavirus disease 2019 (COVID-19). Neutrophils play key role the lung injury characteristic of non-COVID-19 ARDS and there also accumulating evidence neutrophil mediated patients who succumb to infection acute 2 (SARS-CoV-2).</ns3:p><ns3:p> <ns3:bold>Methods: </ns3:bold>We undertook functional proteomic...
Abstract The human Alzheimer’s disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis started near plaques in both AD mouse models and samples. However, endothelial cells express molecular signature of non-productive (NPA) accumulate, plaques, a tip cell marker IB4 reactive vascular anomalies with NOTCH activity. Notably, NPA induction by loss presenilin, whose mutations cause...
Neutrophilic inflammation is central to disease pathogenesis, for example, in chronic obstructive pulmonary disease, yet the mechanisms that retain neutrophils within tissues remain poorly understood. With emerging evidence axon guidance factors can regulate myeloid recruitment and expression of a class 3 semaphorin, SEMA3F, we investigated role SEMA3F inflammatory cell retention inflamed tissues. We observed upregulate response proinflammatory mediators following neutrophil lung. In both...
Background Recent epidemiological evidence has linked hypoxia with the development of Alzheimer disease (AD). A number in vitro and vivo studies have reported that can induce amyloid-β peptide accumulation through various molecular mechanisms including up-regulation precursor protein, β-secretase Bace1, or γγ-secretase complex components, as well down-regulation Aβ-degrading enzymes. Objectives To investigate effects acute chronic sustained Aβ generation vivo. Methods 2–3 month-old C57/Bl6J...
Abstract The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced the dopaminergic neurons of substantia nigra (DA SNpc), both involved nigrostriatal maintenance but reciprocal relationships among these only partially understood. To define postnatal connections...
Neutrophils are essential in the early innate immune response to pathogens. Harnessing their antimicrobial powers, without driving excessive and damaging inflammatory responses, represents an attractive therapeutic possibility. The neutrophil population is increasingly recognised be more diverse malleable than was previously appreciated. Hypoxic signalling pathways known regulate important behaviours and, as such, potential targets for regulating responses.
Summary Understanding the mechanisms by which infection with SARS-CoV-2 leads to acute respiratory distress syndrome (ARDS) is of significant clinical interest given mortality associated severe and critical coronavirus induced disease 2019 (COVID-19). Neutrophils play a key role in lung injury characteristic non-COVID-19 ARDS, but relative paucity these cells observed at post-mortem tissue patients who succumb SARS-CoV-2. With emerging evidence dysregulated innate immune response COVID-19,...
Abstract Microglia respond to Alzheimer’s disease (AD) with a variety of transcriptional responses. However, the regulation specific signatures and contribution each individual response progression is only starting be characterized. We have previously shown that hypoxia via inducible factor 1 (HIF1) strong regulator Aß plaque-associated microglia (AßAM). Here, we characterize role HIF1-mediated transcription Egln3 , encoding for PHD3, in AßAM. show oligomeric treatment (oAß) vitro induces...
Abstract Acute Respiratory Distress Syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, has no cure. Hypoxemia is a defining feature, yet its impact on inflammation often neglected. Patients with ARDS are monocytopenic early in the onset disease. Endotoxin Streptococcus pneumoniae acute lung injury (ALI) context hypoxia replicates this finding, through hypoxia-driven suppression type I interferon signalling. This results failed monocyte-derived interstitial...