Imaging the Cardiovascular Inflammation and the Immune Response
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.