The laboratory focuses on stem cell biology, with an emphasis on hematopoietic differentiation from human and mouse pluripotent stem cells (embryonic stem, ES, and induced Pluirpotent Stem, iPS) cells, epigenetic reprogramming, germ cell development, and the overlap between germ cells, stem cells and cancer. Our goals are described briefly below:
Directed differentiation of hematopoietic stem cells (HSCs) from pluripotent cells: ES/iPS 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/iPS cells to define the molecular genetic programs that enable formation of HSCs in experimental and therapeutic models.
Derivation of genetically defined ES/iPS cells: We use somatic cell nuclear transfer, parthenogenesis, and direct reprogramming in the mouse to model combined cell and gene therapy of human genetic disorders. We develop human models using factor-based reprogramming of somatic cells from patients with a variety of diseases.
Germ lineage, stem cells, and cancer: We are exploring developmental pathways that commonly influence the germ lineage, various stem cell compartments, and tumorigenesis. Most studies focus on the role of the Lin28/let-7 axis, which we have linked to developmental timing, the balance of self-renewal vs differentiation in stem cell populations, and tumor formation, especially in germ cells and blood.
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.
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 464(7286):292-6; online Feb 17; PMID: 20164838.