Research in the North Lab
Dr. North’s laboratory focuses on developmental hematopoiesis as a key to uncovering fundamental principles of stem cell regulation, including specification, self-renewal, regeneration, and cancer. 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. Significantly, intrinsic or extrinsic deregulation of hematopoiesis can result in hematologic disorders and/or malignancies, including leukemia. We use genetic knockdown and epistasis methodologies, together with in vivochemical biology screening approaches in zebrafish to identify pathways regulating hematopoietic niche formation, stem cell induction, and subsequent function. To determine conservation of regulatory effect and translational application, we employ murine HSC development and regeneration assays, and human umbilical cord blood in vitroculture and xenograft models. Our in vivo screening methodology 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.
Our current work examines the following topics in the field of hematovascular biology: 1) characterization of novel regulators of hemogenic endothelium induction and HSC function; 2) the biological rationale for pre-HSC blood formation and shifting hemogenic niches in the vertebrate organism; 3) the impact of immuno-metabolic and environmental factors on embryonic hematovasculogenesis, including relevance to hematologic disease. 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 hematologic disease and enhancing blood stem cell transplantation biology.
Biosketch
Dr. Trista E. North is an Associate Professor at Harvard Medical School (HMS) and Boston Children’s Hospital (BCH) in Boston, Massachusetts, USA. She is Principal Faculty at the Harvard Stem Cell Institute, Faculty of the Biological and Biomedical Sciences Graduate Program at HMS, and a member of the HMS and BIDMC Cancer Centers. Dr. North received a BA from Bowdoin College in 1996, and her PhD from Dartmouth College in 2002. Her graduate work with Dr. Nancy A. Speck examined the function of Runx1 in hematopoietic (blood) stem cell (HSC) development the mouse. Dr. North’s postdoctoral research with Dr. Leonard I. Zon at Boston Children’s Hospital utilized zebrafish to identify novel modulators of Runx1+ HSC production via a chemical screening approach. Dr. North started her own laboratory in the Department of Pathology at BIDMC/HMS in 2008. She returned to Boston Children’s Hospital in 2017. She serves on the board of Directors for the International Society of Experimental Hematology (ISEH), is the editor of the Simply Blood blog, and an editorial board member and guest editor of Experimental Hematology.