Led by Gerd Blobel, MD, PhD, researchers in the Blobel Laboratory are studying the genetic and epigenetic control of hematopoesis in normal and malignant cells. The goal of the research conducted in this laboratory is to gain insights into the transcriptional control of normal hematopoesis in order to identify drug targets that can be used to develop new targeted therapies for the treatment of pediatric hematologic cancers and non-cancerous blood diseases.
Ongoing research in the Blobel Laboratory addresses the question how cell fate is maintained through cell divisions. For example, after each cell division, how do newborn normal and cancerous cells “remember” their state? For example, the Blobel lab found that the transcription factor GATA1 and the gene regulatory protein MLL, which is commonly involved in leukemia-causing chromosomal translocations, play a vital role in maintaining mitotic memory (“mitotic bookmarking”) of hematopoietic cells.
Additional studies in the Blobel Laboratory showed that GATA1 interacted with bromodomain and extra-terminal motif proteins (BETs) in a model system of hematopoietic maturation. Pharmacologic depletion of BETs in this system blunted GATA1-mediated gene activation and interfered with normal hematopoiesis. Drugs that inhibit BET proteins have entered numerous clinical trials, including several for the treatment of acute leukemias. The system that the Blobel lab has developed allows for the dissection of BET protein functions and might lead to the identification of more specific compounds with higher therapeutic potential in childhood leukemias.
Other studies in the Blobel Laboratory, using novel transgenic mouse models, demonstrated that mutations that altered normal FOG1-NuRD complex interactions led to lineage-inappropriate megakaryocyte-erythroid precursor cell gene expression, which interfered with normal megakaryocyte-erythroid cell development. This finding suggested that the FOG1-NuRD complex suppresses lineage inappropriate gene expression during normal megakaryocyte-erythroid cell development.
Another area of emphasis in the Blobel Laboratory is the use of chromatin modifying tools to alter gene expression in red blood cells of patients with sickle cell anemia in a way to cure them permanently.