Stuart Orkin, MD
Boston Children's Hospital
Howard Hughes Medical Institute
The laboratory utilizes multidisciplinary approaches to understand how mammalian cells choose specific fates and how mutations in important transcriptional regulators lead to developmental defects or malignancy. Recent and ongoing work falls into several overlapping areas. First, while many of the essential hematopoietic transcription factors are identified, how they act in the context of other factors within progenitors is less well understood. Hence, we are using biochemical and molecular approaches to address the function of these factors. Second, we are exploring the role of epigenetic modifiers in the biology of hematopoietic stem cells (HSCs), individual hematopoietic lineages, and pluripotent ES cells. Third, we studying the pathogenesis of leukemia and one solid tumor, osteosarcoma, using engineered mice and genomic methods. These studies include modeling one form of infant leukemia in iPS cells. Finally, we have defined the transcription factors critical to developmental regulation of the human globin genes, and are pursuing approaches to the reactivation of the fetal globin genes in adults as a means of therapy for the frequent hemoglobin disorders, sickle cell anemia and beta-thalassemia. Many of the studies in the laboratory have recently employed genetic and chemical screens using complex libraries.
B.S. in Life Sciences at MIT (1967) and M.D. from Harvard Medical School (1972). Research Associate, US Public Health Service (1973-75), Asst. Prof to Professor, Harvard Medical School (1978-1986). Leland Fikes Professor, HMS (1986-2000), David G. Nathan Professor (2000-present) and Chairman of the Department of Pediatric Oncology, DFCI. Member: NAS, IOM, and AAAS. Recipient: AFCR Award (1984), Dameshek Prize of the ASH (1986), Mead-Johnson Award (1987), Warrent Alpert Prize (1993), Helmut Horten Research Award (1995), E. Donnell Thomas Prize of the ASH (1998) and Basic Science Mentor Award (2009), Distinguished Research Award of the AAMC (2005). Chair of the Grants Review Panel of the State of California Stem Cell Institute (2005-2008). Donald Metcalf Award of the International Society of Experimental Hematology (2012).