George Daley
Department of Biological Chemistry and Molecular Pharmacology, Pediatrics, and Medicine Investigator, Howard Hughes Medical Institute
Children's Hospital
Karp Family Research Building 7214
One Blackfan Circle
Boston, MA 02115
Tel: (617) 919-2015
Fax: (617) 730-0222
Email: george.daley@childrens.harvard.edu
18 postdoctoral fellows, 4 graduate students
The laboratory focuses on stem cell biology, with an emphasis on somatic cell reprogramming, hematopoietic differentiation from human and mouse pluripotent stem cells, germ cell development, and mechanisms of oncogenesis. Our specific research programs are described briefly below:
Directed differentiation of HSCs from pluripotent stem cells: We study hematopoietic development in mouse embryos and differentiating cultures of human and mouse pluripotent stem cells to define the molecular genetic programs that enable formation of HSCs in experimental and therapeutic models. Our long-term goal is improved transplantation therapies for genetic and malignant blood disorders.
Derivation of genetically defined pluripotent stem cells: We use nuclear transfer, parthenogenesis, and reprogramming with defined genes to model combined cell and gene therapy of human genetic disorders.
Germ cell development and germ cell tumor biology: We have devised methods for directed differentiation of pluripotent stem cells into primordial germ cells in vitro, which provides an accessible in vitro model system for studying germ lineage commitment. We are studying genetic pathways that preserve pluripotency in the germ lineage and which become deranged in germ cell tumors.
Mechanisms of oncogenesis: We have a long-standing interest in molecular mechanisms of leukemia induction by the BCR/ABL oncoprotein in human Chronic Myeloid Leukemia, the classic malignancy of hematopoietic stem cells. Recent studies in our lab have identified novel genes involved in CML progression to blast crisis. We are currently exploring the Lin-28/let-7 microRNA pathway that we and others have implicated in stem cell self-renewal and oncogenesis.
References:
- Park I-H, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ. Disease-specific induced pluripotent stem cells. Cell 2008 134(5):877-86. Epub 2008 Aug 7; PMID: 18691744.
- Adamo L, *Naveiras O, McKinney-Freeman S, Mack PJ, Suchy-Dicey A, Yoshimoto M, Lensch MW, Yoder MC, #García-Cardeña G, #Daley GQ. Biomechanical forces promote embryonic hematopoiesis. Nature 2009 Jun 25;459(7250):1131-5. Epub 2009 May 13. *equal contribution/ #co-corresponding authors. PMID: 199440194
- Viswanathan S, et al. Lin28 Promotes Transformation and is Associated with Advanced Human Malignancies. Nature Genetics 2009 epub May 31.
- Naveiras O, Nardi V, Wenzel PL, Fahey F, Daley GQ. Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment. Nature 2009 Epub Jun 10.
- West J, Viswanathan SR, Yabuuchi A, Takeuchi A, Cunniff K, Park IH, Sero JE, Perez-Atayde A, Frazier AL, Surani MA, Daley GQ. A role for Lin28 in primordial germ-cell development and germ-cell malignancy. Nature 2009 460(7257):909-13; online July 5. PMID: 19578360 PMCID: PMC2729657
BBS webpage updated 5/11/2010