• Researcher Profile

    Leonard I. Zon, MD

    Leonard I. Zon, MD
    Senior Physician

    Associate Professor of Pediatrics, Harvard Medical School

    Office phone: 617-355-7707
    Fax: 617-355-7262
    Email: zon@rascal.med.harvard.edu

    Preferred contact method: appointment phone

    Research Department

    Pediatric Oncology



    Area of Research

    Developmental Regulation of Hematopoiesis

    Boston Children's Hospital
    300 Longwood Ave.
    Karp 7210
    Boston, MA 02115


    Dr. Zon received his MD in 1983 from Jefferson Medical College, followed by a residency in internal medicine at New England Deaconess Hospital. He served a clinical fellowship in medical oncology at DFCI from 1986 to 1989, when he joined the staff of Children's Hospital and DFCI. His postdoctoral research was in the laboratory of Dr. Stuart Orkin. Dr. Zon is also an associate investigator at Howard Hughes Medical Institute.


    Developmental Regulation of Hematopoiesis

    Our laboratory focuses on the developmental biology of hematopoiesis. Hematopoietic stem cells are derived early during vertebrate embryogenesis. Because the mammalian embryo is difficult to evaluate, as an alternative we have used the zebrafish, which is externally fertilized. The zebrafish embryo is clear, and all organs can be visualized including circulating blood. A large number of animals can be kept in a relatively small space and each mother lays 200 to 300 eggs weekly. These qualities enable a forward genetic approach to vertebrate blood formation. Our studies show that the zebrafish provides information about hematopoiesis relevant to vertebrate biology and to disorders of blood formation.

    Mutant zebrafish. We have collected more than 26 complementation groups of mutants with hematopoietic problems. Peripheral blood and hematopoietic kidney smears were examined. We cloned more than 100 gene homologues of mouse or human factors important in hematopoiesis and evaluated gene expressions by whole-mount in situ hybridization. We developed technology for hematopoietic progenitor assays and stem cell transplantation. Our studies show there are mutants with hematopoietic stem cell defects, proliferation difficulties, and differentiation problems.

    Stem cell biology. We have studied gene expression using whole-embryo in situ hybridization to determine the spatial localization of the hematopoietic program during zebrafish ontogeny. Using complementary DNAs encoding the GATA-binding proteins as probes, we have defined the region of the intermediate cell mass as the equivalent of the yolk sac hematopoiesis. In addition, GATA-2+, GATA-1- cells in the posterior of the embryo appear to represent hematopoietic stem cells. We have characterized in great depth three zebrafish mutations of stem cell formation called bloodless, spadetail, and cloche.

    Hypochromic mutants of zebrafish. There are five complementation groups of mutants with a hypochromic microcytic anemia. This is characteristic of human patients with thalassemia or a defect in hemoglobin production. We initiated a positional cloning approach to isolate the sauternes gene and demonstrated that it was a defect in ALAS-2. The ALAS-2 gene is responsible for heme biosynthesis, and defects in this gene in humans lead to congenital sideroblastic anemia. The fish and human diseases are very similar, and the fish is the first animal model of this human disease.


    • Amatruda, James, MD, PhD
    • Paw, Barry, MD, PhD
    • Trede, Nikolaus, MD, PhD
    • Zhou, Yi, PhD


    • Agarwal, Sadhana, PhD
    • Bahary, Nathan, MD, PhD
    • Davidson, Alan, PhD
    • Ransom, David, PhD
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