Adult stem cells self-renew for life while, at the same time, they proliferate and differentiate into mature cells that replenish their tissues. These abilities open the door to use stem cells in regenerative medicine. Adult stem cells reside in niches that maintain and regulate them. A lot of research focuses on identifying the intrinsic and niche-signals that regulate stem cells. However, little is known about the signals that regulate stem cell activity at the organ and system levels. Our laboratory is focused on understanding the mechanisms by which adult stem cells respond to meet the physiological demands of the organism. We use the hematopoietic system and hematopoietic stem cells (HSC, the ultimate source of all blood cells) as a model system. This is an ideal model because both human and murine HSC are well characterized, easy to isolate and have tremendous clinical applications. Tens of thousands of HSC transplants are done every year to treat malignant and non-malignant diseases. This ensures that new observations can be rapidly translated to the clinic to improve therapy. For our research we use multiple approaches like in vivo genetic (or pharmacological) gain- and loss- of function experiments, lineage tracing, whole organ imaging, hematopoietic stem cell transplantation and mouse chimaeras. We are currently focusing in understanding the role of inflammatory cells and cytokines in regulating HSC function in two conditions: homeostasis and bone marrow failure. We expect this research to discover novel paradigms of stem cell homeostasis that we can manipulate to cure disease.