Lab
North Lab
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Statement of Research Interest
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.
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.
Lab Members
| Dovey, Michael Post-Doc | Polok, Bozena Post-Doc | Harris, James Fish Facility Staff |
| Vedder, Lea Fish Facility Staff |