Research Dr. Palis' research interests are: 1) Ontogeny of the mammalian hematopoietic system, 2) Differentiation of the erythroid lineage, 3) Erythroid precursor self-renewal, and 4) Response of the hematopoietic system to ionizing radiation Hematopoietic stem cells responsible for the production of blood cells throughout life arise during embryogenesis. However, the mechanisms that initiate blood cell development are largely unknown. The long-term aim of Dr. Palis' laboratory is to elucidate the cellular and molecular events underlying the initiation of hematopoiesis in the mammalian embryo. The first hematopoietic cells to emerge during mammalian embryogenesis are "primitive" red cells that are necessary for survival of the fetus. Their recent studies indicate that the primitive erythroid lineage in mice as "mammalian", rather than "non-mammalian" in character. Primitive erythropoiesis will thus serve as an important model of mammalian erythroid differentiation. Hematopoiesis originates in the yolk sac of embryos and transitions to the liver of the fetus. Two waves of hematopoietic progenitors have been identified in the yolk sac prior to colonization of the liver and the lineage composition and relationships of these primitive and definitive progenitor waves are under active investigation. Their studies indicate that the onset of hematopoiesis within the yolk sac of mammals is much more complex than previously thought. The hematopoietic system of the adult is exquisitely sensitive to xenotoxic insults. The Palis laboratory is investigating the response of the erythroid and megakaryocyte lineages to ionizing radiation. These studies will provide for the rational use of cytokines and other agents to mitigate the deleterious effects of external radiation. An understanding of the ontogeny of mammalian hematopoiesis and its response to damage will ultimately produce insights into the regulation and expansion of hematopoietic stem cells. These insights will also lead to a better understanding of genetic disorders, bone marrow failure syndromes and leukemias, ultimately leading to improvements in bone marrow transplantation for the curative treatment of numerous congenital anemias, genetic diseases, and several forms of childhood and adult cancers.