The Daley Laboratory focuses on stem cell biology, with an emphasis on hematopoietic differentiation from human and mouse embryonic stem cells (ES cells), cellular reprogramming, germ cell development, human disease modeling, and the study of the BCR-ABL oncoprotein of chronic myeloid leukemia, the classic malignancy of hematopoietic stem cells (HSCs). Our primary research areas are:
- Directed differentiation of HSCs from pluripotent cells: Mechanisms of directed differentiation and models for functional engraftment in diseased animals remain poorly defined. We study hematopoietic development in mouse embryos and differentiating cultures of human and mouse pluripotent stem cells in order to define the molecular genetic programs that enable formation of HSCs in experimental and therapeutic models.
- Derivation of genetically defined pluripotentstem cells: We use somatic cell nuclear transfer parthenogenesis and direct reprogramming to model disease and development
in the mouse.
- germ cell development: We have devised methods for directed differentiation of pluripotent stem cells into primordial germ cells and techniques for isolation and functional transplantation
of spermatagonial stem cells from testes. Using this integrated system, we are exploring strategies for in vitro maturation of pluripotent cell-derivedgerm cell populations into functional gametes, as well as studying the development of germ-cell related malignancies of the reproductive system.
- Target-directed chemotherapy for human malignancy: We characterize the mechanisms of action and modes of resistance of target-directed chemotherapy for the treatment of CML and other cancers and use chemical genetics to probe mechanisms of kinase regulation. Using techniques for molecular monitoring of resistance patterns in patients, we are seeking to define optimal combination chemotherapy regimens.
- Cellular reprogramming: Our laboratory was among the first groups in the world to show that mature cells obtained from a patient’s biopsy are capable of being reprogrammed to an embryonic-like state. We are currently using these induced pluripotent stem cells to advance our understanding of congenital and acquired diseases, with an ultimate goal of creating patient-matched cells for transplantation therapy. Science Magazine cited our work as as contributing to the Scientific Breakthrough of the Year for 2008.
Please visit the Daley Laboratory for more information. For a virtual tour of the Daley Lab, please view our video. For a full list of Daley publications, please visit PubMed.