Bone marrow derived hematopoietic stem cells give rise to all blood cell types among which are myeloid cells that constitute an essential arm of innate immunity. This hierarchical cell fate decisions process is orchestrated by key transcription factors. These factors govern and modulate the expression of lineage specific genes. Aberrant expression of these key regulators results in block in the differentiation process and subsequently leads to leukemias. Lineage specific expression is the hallmark of this complex differentiation process, yet the molecular mechanisms that govern this lineage restricted expression are not elucidated.
Our research is focused on the molecular mechanisms that govern transcriptional regulation of genes in general and during myeloid cell differentiation in particular. We study a transcription factor termed IRF-8, which is essential for the ability of progenitor cell differentiation toward the monocyte arm of the myeloid cells. We demonstrate that epigenetics modifications are essential for this lineage specific expression. Further, we study gene regulatory network governed by IRF-8 and its role in the differentiation process, the activity of the mature cells and the suppression of leukemias. Our research will allow future drug design to manipulate the immune system and to eliminate cancer cells and invading pathogens.
Molecular Biotechnology, Mechanisms of gene regulation in the immune system; the effect on pathogen resistance and the emergence of myeloid-leukemias