Leonard I. Zon, M.D.
Boston Children's Hospital
Harvard Medical School
The Zon laboratory aims to dissect how assaults to the hematopoietic system cause severe diseases such as leukemias, lymphomas, and anemias. They investigate hematopoietic development and disease using chemical screens, genetic screens, and analysis of novel transgenic lines in zebrafish.
Research in the Zon lab focuses on the developmental biology of hematopoiesis and cancer. Over the past five years, they have collected over 30 mutants affecting the hematopoietic system. Some of the mutants represent excellent animal models of human disease. For instance, the isolation of the ferroportin iron transporter was based on a mutant zebrafish and subsequently was shown to be mutated in patients with iron overload disorders. The mutants also represent interesting key regulatory steps in the development of stem cells. Recently, a mutant was found that lacked blood stem cells and the mutated gene proved to be a caudal related homeoprotein called, CDX4. A Cdx-hox pathway was found to participate in early hematopoietic stem cell development and overexpression of CDX4 leads to ectopic blood development, within the zebrafish embryo and in mouse embryonic stem cells. We recently have developed hematopoietic cell transplantation for the zebrafish using blood cells labeled with green fluorescent protein and DSred. Zon lab researchers were able to image the hematopoietic cells as they migrate to the marrow and to the thymus.
The group has also developed zebrafish models of cancer. A screen for cell cycle mutants found 19 mutants. Some of these mutants get cancer at a very high rate as heterozygotes based on a carcinogenesis assay. The mutant genes appear to be new cancer genes and Zon has used small molecules in a chemical suppressor gene to find chemicals that bypass the mutant cell cycle problem. The lab has also generated a melanoma model in the zebrafish system using transgenics. Transgenic fish get nevi, and in a combination with a p53 mutant fish develop melanomas.
Dr. Leonard I. Zon is the Grousbeck Professor of Pediatric Medicine at Harvard Medical School, an Investigator with the Howard Hughes Medical Institute, and Director of the Stem Cell Program at Boston Children's Hospital. He received a B.S. in chemistry and natural sciences from Muhlenberg College and an M.D. from Jefferson Medical College. He subsequently did an internal medicine residency at New England Deaconess Hospital and a fellowship in medical oncology at Dana-Farber Cancer Institute. Dr. Zon is President of the International Society for Stem Cell Research, President of the American Society for Clinical Investigation, Head of the external investigators of the Zebrafish Genome Institution and Chairman of the Harvard Stem Cell Institutes Executive Committee.
Dr. Zon is internationally recognized for his pioneering research in the new fields of stem cell biology and cancer genetics. His current research focuses on two critical avenues of investigation: identifying the genes that direct stem cells to become cancers or to develop into more specialized blood or organ cells, and developing chemical or genetic suppressors to cure cancers and many other devastating diseases.