Associate Professor of Pathology, Harvard Medical School
Stem Cell Program, Department of Hematology/Oncology, Boston Children's Hospital
Children's Hospital, Dr. Leonard Zon, postdoctoral research fellowship
Dartmouth College, Ph.D. (2002)
Bowdoin College, B.S. (1996)
Regenerative medicine holds great promise to alleviate morbidity and mortality in patients suffering from organ failure. Pathways that govern stem cell behavior and organ development can be modulated to affect adult organ repair and regeneration. Our laboratory focuses on developmental hematopoiesis as a key to uncovering general principles of stem cell function, self-renewal and tissue regeneration. Hematopoietic stem cells (HSCs) give rise to each of the blood lineages found in the adult vertebrate; the gene programs regulating HSC development and homeostasis are highly evolutionarily conserved. We are using the zebrafish as a model system to discover novel regulators of HSC formation. In addition, we employ murine models to document evolutionary conservation of these signaling pathways during development and in hematopoietic regeneration following injury or transplantation.
Through a chemical genetic screening approach, we identified several novel compound modifiers of blood stem cell formation; each pathway isolated in the screen altered the normal expression pattern of the conserved HSC marker runx1. This methodology led to the first example of FDA approval for the investigational use of a compound identified in an unbiased screen in zebrafish for clinical application in the treatment of human disease. Our laboratory will use both chemical and genetic approaches in the zebrafish to characterize novel mechanisms controlling HSC induction in the vertebrate embryo. Additionally, through comparative genomic examination of zebrafish and murine sites of embryonic hematopoiesis, we aim to decipher regulatory networks that are central to HSC formation and function. Using chemical ablation, irradiation injury and transplantation approaches, we will further define the functional conservation of HSC regulators identified in the embryonic screens in controlling adult marrow homeostasis in zebrafish and mice. Xenotransplantation experiments using human cord blood with be employed to investigate translational potential. The work in our laboratory has direct relevance for the development of novel therapeutic strategies for controlling leukemogenesis and enhancing stem cell transplantation biology.
NIH NIDDK R01 and URM Supplement
Leukemia and Lymphoma Society Scholar Award
HSCI Seed Grant
American Society of Hematology Junior Faculty Scholar Award
HSCI Junior Faculty Program Grant
HSCI Blood Program Project Grant
V Foundation for Cancer Research Scholar