Trista E. North
Department of Pathology
Center for Life Sciences Building, Room 636
3 Blackfan Circle
Boston, MA 02115
Visit my lab page here.
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 will 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.
Goessling W, Allen RS, Guan X, Jin P, Uchida N, Dovey M, Harris JM, Metzger ME, Bonifacino AC, Stroncek, D, Stegner J, Armant M, Schlaeger T, Tisdale JF, Zon LI, Donahue RE, North TE. Prostaglandin E2 enhances engraftment of human umbilical cord blood stem cells and is safe for use in preclinical primate and xenotransplantion models. 2011. Cell Stem Cell 8: 445-458.
North, TE*, Goessling W*, Peeters M, Li P, Ceol C, Lord AM, Weber GJ, Harris J, Cutting CC, Huang P, Dzierzak E, Zon LI. 2009. Cell 137: 736-748.
Goessling W*, North TE*, Schmitt S, Lord AM, Lee S, Stoick-Cooper C, Puder M, Daley GQ, Moon RT, and Zon LI. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. 2009. Cell 136: 1136-1147.
North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord A, Weber G, Bowman T, Jang IH, Grosser T, FitzGerald GA, Daley GQ, and Zon LI. Prostaglandin E2 regulates zebrafish hematopoietic stem cell homeostasis. 2007. Nature 447: 1007-1011.
For a complete listing of publications click here.
Last Update: 7/26/2012