Lab: Brand Lab
Our main research interest is the regulation of gene expression at the level of transcription and chromatin. In particular we focus on the transcriptional regulatory network that controls hematopoietic stem cell differentiation towards the erythroid lineage. Hematopoietic Stem cells have the capacity to differentiate along multiple lineages potentially giving rise to all cells present in the blood. This process is controlled by cell-specific and ubiquitously expressed transcription factors and cofactors. Defects in the transcriptional regulatory network of these cells can lead to leukemia. The major goal of our lab is to decipher the molecular mechanism of hematopoietic stem sell differentiation towards the erythroid lineage and to understand how deregulation of this process can cause leukemia. Towards this goal, we are using a systems biology approach that applies quantitative proteomics (isotope tagged methods such as ICAT, iTRAQ and SILAC), genomics (expression microarray, ChIP-sequencing) and bioinformatics in hematopoietic cell systems to understand the regulation of gene expression at the level of transcription, epigenetics and chromatin structure. Notably, we are employing a recently developed cell culture protocol to induce differentiation of red blood cells ex vivo from human hematopoietic stem cells that have been extracted from blood, bone marrow or cord blood. This system provides us with large quantities of cells at various stages of hematopoietic differentiation to perform genomics and proteomics experiments. Together these studies will help elucidate the molecular mechanism by which oncogenes alter cell-fate memory in the hematopoietic lineage leading to leukemic transformation.