We are interested in understanding the cell fate decision processes: how does a cell know what to be and what not to be? We use two primary biological model systems to investigate this question.
1. Induced pluripotency (Yamanaka reprogramming). How does a somatic cell abandon its own identity and take on pluripotency as a new identity? This process is rare but does not occur randomly. We are interested in the rare cells that undergo cell identity switching at high efficiency. We are particularly interested in a subset of hematopoietic progenitors that can undergo cell fate switching with extraordinarily high efficiency. These cells and others help us to understand the mechanism that enable high efficiency cell fate switching.
2. Maintainence of the hematopoietic stem and progenitor cell fate. Our recent work has determined that the same rare cells mentioned above, a subset of rapidly dividing hematopoietic progenitors, undergo MLL-AF9 mediated malignant transformation with high efficiency: the oncogene perpetuates this highly proliferative cell state. Therefore, the proliferative state precedes the oncogene activity and promotes transformation. We are actively working on elucidating the mechanisms that maintain or perpetuate the hematopoietic progenitor cell fate.
Overall, our long term goal is to deduce the rules of cell fate control to help create desired cell types for cell replacement therapies and to eliminate the emergence of harmful cell types such as cancer.
Specialized Terms: Cell fate control; Reprogramming; Hematopoietic stem and progenitors; Leukemogenesis; Cell cycle; live-cell imaging
Cell Biology; Hematopoietic Stem Cells; Leukemia, Experimental; Cellular Reprogramming