George Q. Daley
 George Q. DaleyChildren's Hospital Boston
Harvard Medical School
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Research Summary
The laboratory focuses on stem cell biology, with an emphasis on hematopoietic differentiation from human and mouse ES cells, germ cell development, and study of the BCR-ABL oncoprotein of chronic myeloid leukemia (CML), the classic malignancy of hematopoietic stem cells (HSCs). These research thrusts are described below:
Directed differentiation of HSCs from ES cells: ES cells are pluripotent, yet 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 ES cells in order to define the molecular genetic programs that enable formation of HSCs in experimental and therapeutic models.
Somatic cell reprogramming: We use somatic cell nuclear transfer in the mouse to model combined cell and gene therapy of human genetic disorders (therapeutic cloning). We are studying the fundamental mechanisms involved in epigenetic reprogramming, and exploring alternative means beyond nuclear transfer to reprogram somatic cells.
Self-renewal and differentiation of human ES cells: We are using expression cloning together with genomic and proteomic strategies to identify factors that specify human ES cell self-renewal and differentiation. We are building tools for gene expression in human ES cells to facilitate future experimental and therapeutic studies.
Germ cell development: We have devised methods for directed differentiation of ES cells into primordial germcells, 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 ES-derived germ cell populations into functional gametes.
Target-directed chemotherapy for human CML: We have characterized the mechanisms of action and modes of resistance of target-directed chemotherapy for the treatment of CML. Our current studies are aimed at defining optimal combination chemotherapy regimensand mechanisms of clinical resistance in human trials.
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Bio-Sketch
George Q. Daley, M.D., Ph.D. is Associate Professor of Pediatrics in the Division of Hematology/Oncology at the Children's Hospital and Dana Farber Cancer Institute and Associate Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. He received a bachelor's degree magna cum laude from Harvard University (1982), a Ph.D. in biology from MIT (1989), and the M.D. degree summa cum laude from Harvard Medical School (1991). Dr. Daley's laboratory studies stem cell development and differentiation, emphasizing derivation of functional hematopoietic and germ cell elements from ES cells, and the genetic mechanisms that predispose to malignancy. Dr. Daley is Board Certified in Internal Medicine and Hematology, and is currently a staff physician in Hematology/Oncology at the Children's Hospital, the Dana Farber Cancer Institute, and the Brigham and Women's Hospital in Boston. He has been elected to the American Society for Clinical Investigation, and has received research awards from Harvard Medical School, the National Institutes of Health, the New England Cancer Society, the Burroughs Wellcome Fund, the Edward Mallinckrodt, Jr. Foundation, and the Leukemia and Lymphoma Society of America. He received the inaugural NIH Directors Pioneer Award, a five-year unrestricted grant to pursue highly innovative research.
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