The overall theme of Dr. Silberstein's laboratory is to understand the mechanisms by which niche-specific signals in the bone marrow microenvironment influence hematopoiesis.
Both the localization and migration between bone marrow niches of hematopoietic progenitor cells depend on cell-cell and cell matrix interactions, which result from the cooperation of cytokine receptors, chemokine receptors, and adhesion molecules. Using B lineage differentiating bone marrow cells as a model, the laboratory wishes to define the molecular signaling pathways of the CXCL12/CXCR4 chemokine axis. Although the axis appears to play a major role in hematopoietic progenitor/homing engraftment in the bone marrow as well as retention in the bone marrow for normal hematopoietic development, the mechanisms by which these processes occur remains largely unknown.
By better understanding the molecular signaling pathways of the CXCL12/CXCR4 axis, the laboratory hopes to devise strategies to improve stem/progenitor cell engraftment following transplant. Laboratory methods include both molecular and cellular approaches of human and murine cells and the use of gene targeted animal models.