Hematopoietic stem cells (HSCs) can give rise to each of the blood lineages present throughout a vertebrate’s lifetime. The gene programs and signaling networks regulating HSC development and function in the embryo and adult are highly evolutionarily conserved, with dysregulation resulting in hematologic disorders or malignancies, such as anemia, leukemia and lymphoma. HSCs are therapeutically valuable for the treatment of blood disease, but are in limited supply and currently cannot be effectively expanded or produced de novo in culture. My laboratory utilizes genetic methods and chemical biology approaches in zebrafish to identify and characterize pathways regulating HSC induction, expansion and function in vivo; to examine conservation of regulatory effect and translational application, we employ both murine and human in vitro culture assays, and in vivo HSC functional analyses.

This in vivo screening methodology and cross-species functional validation led to the first example of FDA approval for the investigational use of a compound [Prostaglandin E2 (PGE2)] identified in zebrafish for clinical application in the treatment of human disease. Research in the North lab has led to the identification of a series of extrinsic cues that influence the spatio-temporal development, expansion and maintenance of HSC production across vertebrates, including essential roles for metabolic, inflammatory and biomechanical signals, which are conserved across species. Ongoing investigations in the lab are focused on the following topics in the field of hemato-vascular biology: 1) regulation of hemogenic endothelium commitment and HSC production in vivo and in vitro; 2) rationale for pre-HSC blood formation and shifting hemogenic niches in the vertebrate embryo; 3) the impact of environmental factors on developmental hematopoiesis, including relevance to onset and progression of blood disorders and diseases. Trainees in the North lab have successfully competed for independent funding, have been selected for oral presentations and awards at international conferences, and have transitioned to highly productive postdoctoral, scientist and leadership positions in academia and industry. Together, our prior and ongoing work broadens our understanding of vertebrate HSC formation, expansion and differentiation, which has direct relevance for the development of novel therapeutic strategies for controlling hematopathologies and enhancing blood stem cell transplantation.