Our laboratory is interested in innate immune cells. Macrophages, a major cellular component of innate immunity, are conspicuously present in most organs in which they are endowed with specialized phenotypes and functions that support normal tissue integrity. How they acquire these properties in certain organs, like the heart, is unknown. One of our goals is to define how the heart instructs macrophages to perform its homeostatic functions, and to precisely define what these functions are. As macrophages are bona fide phagocytic cells, we also study how phagocytosis is executed in each tissue, its molecular mediators, and the consequences of phagocytosis in tissue-resident macrophages.

Another area of our interest relates to neutrophils, the most abundant innate immune cells. These leukocytes are highly migratory and essential to fight off invading microbes, but at the same time can cause collateral damage to the vasculature, a process that is important in many cardiovascular events from stroke to myocardial infarction. We study regulatory mechanisms in neutrophils that boost immune defense but limit vascular injury, as they may have high therapeutic value. In particular we focus on temporal regulation of neutrophils because these leukocytes display strict circadian patterns both in numbers and phenotype (Casanova-Acebes, Cell 2013). Because regulators of circadian time may be one of the mechanisms that ensures that immune defense and vascular integrity are compatible, we have generated various lines of mutant mice to understand how time controls the protective and aggressive functions of neutrophils. We also use high-resolution imaging in live tissues by multichannel intravital microscopy to visualize how neutrophils reach the site of inflammation and how they coordinate with other cell types, including platelets, to decide where and when to act (Sreeramkumar, Blood 2013; Chèvre, Circ. Res. 2014; Sreeramkumar, Science 2014).

Immune cells originate through proliferation and differentiation of hematopoietic stem cells (HSC), a rare population that resides mainly in the bone marrow and is maintained within dedicated hematopoietic niches in this organ. We devote efforts to understand how HSC proliferate, are maintained in, or mobilized from the bone marrow (Leiva, Nat. Commun. 2016). We are also interested in the mechanisms by which several types of niche cells maintain a functional population of HSC.