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Strategic Objective
In the setting of the systemic response frequently found in patients attended in Internal Medicine wards, our group has studied some regulatory mechanisms of the innate immune response in patients with sepsis and other inflammatory states such as acute coronary syndromes (ACS), cystic fibrosisand cancer.
The first line of our research is the link between the parasympathetic and innate immune systems, that is the molecular mechanisms by which acetylcholine can influence the immune system via the “cholinergic anti-inflammatory pathway”.
This pathway is mediated by the vagus nerve whichreleases acetylcholine to interact with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR).
We firstly reported that the neuronal α7 nicotinic receptor subunit gene (CHRNA7) is partially duplicated in the human genome forming a hybrid gene (CHRFAM7A) with the novel FAM7A gene, and provided experimental data showing that dupα7 could modulate α7 receptor-mediated synaptic transmission and cholinergic anti-inflammatory response (J Biol Chem 2011). The Toll-like receptor (TLR) plays an important role in the induction of the hyperinflammatory response and tissue injury in sepsis. We found that the α7 gene expression level in septic patients’ peripheral blood mononuclear cells (PBMC) is a clinically relevant marker to assess the magnitude of the patient’s inflammatory state, disease severity, and clinical outcome (J Infect Dis 2015).
Another exciting line of our research is the involvement of the α7-nicotinic receptor and its endogenous modulator dupα7 in human smoking- related tumors, and particularly their involvement in tobacco carcinogen-induced tumor development and chemotherapy resistence. This topic has attracted a grant from the Ministerio de Economia y Competitividad from 2014-2017. Besides, professor Jaime Renart who works in our team group, is doing new research on the molecular mechanisms of podoplanin, a type I transmembrane mucin widely known as a marker for lymphatic endothelial cells that has a critical role during development of the heart, lungs and lymphatic endothelial system. The expression of podoplanin is significantly enhanced during tissue-remodelling processes and in several types of human cancer, including squamous cell carcinomas.
Research Lines
Applied research lines:
• Molecular mechanisms involved in the innate immune response.
• Link between the parasympathetic and innate immune systems.
Collaborative research line:
• Adaptative imnune response in human immunodeficiency virus (HIV) infection.
• Multicentric group: RIETE group (Registro Español de Enfermedad Trombo-Embólica).
• Molecular mechanisms of podoplanin during tissueremodelling processes and in several types of human cancer.
• Mechanisms and clinical features of systemic autoimmne diseases.
Lines of study framed in basic research projects:
• Study of the pathophysiological role of nicotinica7 and dup-a7 receptors expressed in human macrophages, neurons and lung carcinoma cells.
• Identification of signalling pathways connecting nicotinic alpha7 receptors and negative regulators of TLR-mediated inflammation in human macrophages.
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