BBS Faculty Member - Stuart Orkin

Stuart Orkin

Department of Pediatric Oncology, DFCI

Boston Children's Hospital and Dana Farber Cancer Institute
Howard Hughes Medical Institute/ Harvard Stem Cell Institute
450 Brookline Ave.
Boston, MA 02215
Tel: 617-919-2042
Fax: 617-730-0222
Lab Members: 15 postdoctoral fellows, 1 graduate student, 1 visiting student, 1 rotation student

Molecule analysis of blood cell development has served as an important paradigm for stem cell biology. We have obtained a solid foundation in understanding how commitment to specific lineages is programmed and cell-specific patterns of gene expression are established. We are interested in how hematopoietic, and other, stem cells transcriptionally control developmental potency and how aberration may precipitate oncogenesis.

Our studies have focused primarily on the in vivo roles of transcriptional regulators in cell specification and differentiation. Studies involved diverse approaches, including conventional and conditional gene targeting, and proteomics. We have characterized the roles of several major transcription factors in blood cell development, and how abnormalities in these lead to malignancy. Ongoing projects include the following: 1. Epigenetic regulation of hematopoietic stem cells, individual blood lineages, and ES cells; 2. Dissecting the genetics of one form of early childhood leukemia using hES and iPS cells; 3. Modeling osterosarcoma in the mouse with the goal of developing new approaches to controlling or preventing metastases; 4. Defining the control of fetal hemoglobin (HbF) in humans and reactivation of HbF in adults; and 5. Chemical and biological approaches to HbF reactivation.

Last Update: 8/22/2013


For a complete listing of publications click here.



Sankaran, V.G., Xu, J., Ragoczy, T., Ippolito, G.C., Walkley, C.R., Maika, S.D., Fujiwara, Y., Ito, M., Groudine, M., Bender, M.A., Tucker, P.W., and Orkin, S.H. Developmental and species-divergent globin switching are driven by BCL11A. Nature 460: 1093-1098, 2009.

Kim, J., Woo, A.J., Chu, J., Snow, J., Fujiwara, Y., Kim, C.G., Cantor, A.B., and Orkin, S.H. A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs. Cell 143: 313-24, 2010.

Xu, J., Peng, C., Sankaran, V.J., Shao, Z., Esrick, E.B., Chong, B.G., Ippolito, G.C., Fujiwara, Y., Ebert, B.L., Tucker, P.W., and Orkin, S.H. Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science, 334: 993-996, 2011.

© 2013 by the President and Fellows of Harvard College