Future advances in the field of infectious diseases will be based on an improved understanding of host-pathogen interactions. The host immune system can be viewed as a product of hematopoietic stem cells that reside in the bone marrow. My research is focused on how the composition of the immune system is regulated, starting at the level of the hematopoietic stem cell. We have found that inflammatory signals, particularly interferon gamma, influence the proliferation and differentiation of hematopoietic stem cells during infection, thus shaping the immune response as a whole. We use two model pathogens, Mycobacterium avium and lymphochoriomeningitis virus, in a murine model to study these effects in vivo.
This work provides insight into how immune cells are sustained during infection, when the demand for immune effector cells is dramatically increased. We are interested in the ways that such short term hematopoietic stem cell responses may ultimately contribute to syndromes of bone marrow dysfunction that are related to infection or inflammation, such as bone marrow suppression following tuberculosis and HIV/AIDS or acquired aplastic anemia as a result of EBV infection. This research will lead to critical insights into the basic biology of hematopoietic stem cell function, including how inflammation may contribute to hematologic changes seen in aging and cancer.