Adult stem cells are the source of committed, proliferating and differentiating cells during development and homeostasis, and the dysregulation of stem cell behavior is a major contributing factor to cancer. The Hematopoietic Stem Cells (HSCs) are self-renewing multipotent adult stem cells that produce all types of mature blood cells throughout the life of an organism. Given its importance in development and disease, it is essential to understand the underlying mechanisms behind the proper maintenance of hematopoietic stem and progenitor cells.
In complex vertebrate models, these questions are all harder to address, while the robust genetics of Drosophila allows for an in-depth analysis of these clinically relevant problems. The Drosophila provides an excellent model system for these investigations because it has only three types of mature blood cells, which act as the human myeloid lineage and the high degree of conservation of blood development between Drosophila and humans. Our scientific endeavors are focused towards understanding the developmental logic of blood cells by manipulation of gene function.
HSCs are uniquely capable of keeping their genomic integrity to retain life-long functionality. It is unclear how they achieve this skill. Recent studies have shown that DNA Damage Response (DDR) pathways are critical in preserving the quiescent HSCs. Alteration of DDR and repair pathways in HSCs cause cells entry into cell cycle that leading to HSCs exhaustion. Moreover, HSCs accumulate DNA damage during aging. Consequently, it leads to a poor immune response and the development of myeloid leukemia in old age. The underlying molecular mechanisms of how DDR and repair pathways impinge upon proper maintenance of stem and progenitor cells have not been addressed. We will use Drosophila blood system as an in vivo model to find novel mechanism that potentially involved in human hematopoiesis for proper maintenance of hematopoietic stem and progenitor cells. We intend to apply in vivo genetics, genomics, and cell biological approaches to address this problem. We hope that our research will uncover novel genes and mechanisms that are potentially relevant in the human hematopoiesis and leukemia.