Molecular mechanisms of bone marrow regeneration

Macrophages initiate immune responses to infection, but aberrant macrophage activation may lead to organ damage and loss of stem cell functions. In the context of hematopoietic stem cell (HSC) gene therapy, alleviation of unwanted inflammation is critical to preserve the engraftment and regenerative capacities of gene-modified stem cells. We recently identified a transcriptional circuit enabling control of inflammatory gene expression in macrophages. In this project, we will combine advanced genomics and proteomics, computational analyses, and functional experiments to study the role of the PGE₂-MEF2A axis in the bone marrow microenvironment. Successful completion of the proposed research will uncover regulatory principles and mechanisms of tissue immune homeostasis and regeneration, with direct implications for HSC gene therapy.