Our laboratory is interested in the biology of inflammation and immune cells. We are developing techniques based on multichannel fluorescence intravital microscopy to visualize the molecular and cellular phenomena that occur within the inflamed vasculature. We are also interested in understanding the mechanisms by which leukocyte production and clearance modulates tissue homeostasis.
Imaging inflammation: Leukocytes and platelets are recruited to inflamed vessels via adhesion receptors, chemokines and cytokines. During this process, leukocytes redistribute surface receptors to discrete domains, each of which can mediate interactions with circulating platelets and erythrocytes. These interactions can lead to an excessive activation of the leukocyte, which in turn releases toxic mediators that damage the surrounding endothelium (Hidalgo et al., Nat. Medicine 2009). We wish to understand the biology of these interactions, including how they lead to the formation of polarized leukocyte domains, the identity of the receptors that mediate them, and their consequences in inflammatory processes. We are particularly interested in understanding the potential contribution of these interactions during atherosclerosis.
Neutrophils as regulators of homeostasis: We wish to dissect the links between inflammation and hematopoietic niches in the bone marrow, the home of hematopoietic stem cells and their differentiating progeny. We are addressing this through the use of gene-targeted mouse models with alterations in the immune and hematopoietic systems. Our long-term goal is to define how leukocyte production and elimination governs the normal or pathological functions of many organs in the body (Casanova-Acebes et al., Cell 2013; A-Gonzalez et al., Nat. Immunol. 2013).
Cell competition between hematopoietic stem cells: Cell competition is a biological process that selects for the fittest cells through induction of apoptotic death in the less fit population. First described in Drosophila, and very recently in the mouse embryo (Clavería et al., Nature 2013), this phenomenon serves to optimize tissue function. We are studying whether this mechanism also operates in the hematopoietic stem cell compartment of mice.
Legend for image panel: (Top left to bottom right) (1) Images from an intravital experiment of the inflamed vasculature of the cremaster muscle, in which we can identify and compare the behavior of leukocytes of different genotype on the basis of endogenous fluorescence, in this case mutant cells are detected by contrast and wild-type cells by expression of DsRed (red). (2) Inflammatory neutrophils (contrast) displaying polarization of the surface receptor L-selectin (blue) capture platelets (red) from the circulation. (3) Electron micrograph of an “aged” neutrophil. (4) Neutrophils physiologically cleared in the spleen of a mouse can be identified by GFP expression (green) in close interaction with red-pulp macrophages (red). Some neutrophils are actively engulfed by tissue macrophages (white arrow).
Andrés Hidalgo se licenció en CC. Biológicas por la Universidad Autónoma de Madrid en 1993, y se doctoró por la misma universidad en 1999 tras trabajar en control de la adhesión hematopoiética, en el laboratorio del Dr. Joaquín Teixidó (Centro de Investigaciones BIológicas, Madrid). En 2000 se mudó a Nueva York, donde se centró en entender los procesos de migración de leucocitos y células madre hematopoiéticas, así como procesos inflamatorios, en el laboratorio del Dr. Paul Frenette (Mount Sinai School of Medicine). Tras conseguir un contrato de reincorporación Ramón y Cajal, se incorpora como Investigador Junior II en el departamento de Aterotrombosis e Imagen Cardiovascular.del CNIC en 2008.