Stem Cell Program Labs
GeorgeDaleyLab_Edited

The Daley Lab

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-derived germ 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.

For a virtual tour of the Daley lab, please view our video.

SELECTED REFERENCES

Kim K, Lerou P, Yabuuchi A, Lengerke C, Ng K, West J, Kirby A, Daly M, Daley GQ. Histocompatible embryonic stem cells by parthenogenesis. Science 2007 315(5811):482-6. Epub 2006 Dec 14; PMID: 17170255.

Park I-H, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, and Daley GQ. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2008 451(7175):141-6. Epub 2007 Dec 23; PMID: 18157115.

Lerou PH, Yabuuchi A, Shea J, Takeuchi A, Cimin T, Ince T, Ginsburg E, Racowsky C, Daley GQ. Human embryonic stem cell derivation using poor quality embryos. Nature Biotechnology 2008 26(2):212-4. Epub 2008 Jan 27; PMID: 18223642.

Viswanathan S, *Daley GQ, *Gregory RI. Selective blockade of microRNA processing by Lin-28. Science 2008 320(5872):97-100 [Epub February 21]; PMID: 18292307.

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; PMCID: PMC2633781.

*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; PMID: 19440194.

Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ. Bone Marrow Adipocytes as Negative Regulators of the Hematopoietic Microenvironment. Nature 2009 Jul 9;460(7252):259-63. Epub 2009 Jun 10; PMID: 19516257.

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 germ cell development and germ cell malignancy. Nature 2009 460(7257):909-13; online July 5; PMID: 19578360; PMCID: PMC2729657.

Agarwal S, Loh Y-H, McLoughlin EM, Huang J, Park I-H, Miller JD, Huo H, Rosana Okuka M, Maria dos Reis RM, Loewer S, Ng, H-H, Keefe DL, Goldman FD, Klingelhutz AJ, Liu L, and Daley GQ. Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature 2010 online Feb 17; PMID: 20164838.

Giving

Spotlight

  • Embryonic stem cells teach lessons about Fanconi anemia

    Children with Fanconi anemia, a rare genetic disease, often begin experiencing low blood cell counts at about age 7, and can die unless they get a bone marrow transplant. Now, by modeling Fanconi anemia in the lab using human ES cells, researchers at Children’s Hospital Boston reveal that inadequate production of blood cells may actually begin long before birth, casting a whole new light on the disease. ES cells were used because past research has shown Fanconi anemia to be difficult to model with induced pluripotent cells
    . Read more.