Molecular and Developmental Hematopoiesis
Hematopoietic Stem Cells (HSCs) provide the foundation of the hematopoietic system in vertebrates. Being multipotent and capable of self-renewal, HSCs are responsible for constant production of all blood cell types throughout life. Because of their properties, HSCs are highly demanded in clinic daily. For example, HSCs are used for replenishing the hematopoietic system of acute myeloid leukemia (AML) patients after chemotherapy or for patients that need blood transfusions. However, due to their limited number and our inability to expand them sufficiently in vitro, it has so far been impossible to provide for these extensive needs. In addition, alterations in the properties of HSCs and their environment lead to disease. In order to expand HSCs or cure hematopoietic malignancies arising from them, we need to understand the network of signals that govern their fate from the time they develop till maturity.
We focus particularly on the effect of endogenous and exogenous signals in hematopoiesis. We recently found that repetitive/transposable elements are expressed during developmental transitions and especially during hematopoietic stem cell formation. The RNA of repetitive elements triggers innate immune receptors like RIG-I-like receptors and leads to their activation. This was surprising, since RNA sensors are usually used by cells for the detection of viral RNA deriving from invading pathogens. However, in our system, RNA from endogenous repetitive elements signals through these receptors and causes a sterile inflammation that is helpful in hematopoietic stem cell formation (Lefkopoulos et al., Immunity 2020). We believe that repetitive elements play a role in adult hematopoiesis, especially under stress situation where quiescent hematopoietic stem cells need to be activated, exit quiescence and start cycling. In particular, we are very interested in chemotherapy since its wide medical use makes our research pertinent to human health.
In our lab we have several projects spanning different aspects of developmental and regenerative hematopoiesis and disease:
- Role of repetitive elements in hematopoietic stem cell development and regeneration
- Molecular mechanisms that govern hematopoietic stem cell activation after chemotherapy.
- The role of RNA sensors in hematopoietic disease