BBS Faculty Member - Trista North

Trista North

Department of Hematology/Oncology
Stem Cell Program


Boston Children's Hospital
Karp Family Research Building, 05214
300 Longwood Ave.
Boston, MA 02115
Tel: 617-919-6410
Fax: 617-735-2480
Email: trista.north@childrens.harvard.edu
Visit my lab page here.



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.



Last Update: 9/25/2020



Publications

For a complete listing of publications click here.

 


 

Frame JM, Kubaczka C, Long TL, Esain V, Soto RA, Hachimi M, Jing R, Shwartz A, Goessling W, Daley GQ, North TE. Metabolic regulation of inflammasome activity controls embryonic hematopoietic stem and progenitor cell production. 2020. Developmental Cell Aug 10;S1534-5807(20)30589-X doi: 10.1016/j.devcel.2020.07.015. Online ahead of print. PMID: 32810442

Lundin V*, Sugden WW*, Theodore LN*, Sousa PM, Han A, Chou S, Wrighton PJ, Cox AG, Ingber DE, Goessling W, Daley GQ, North TE. YAP Regulates Hematopoietic Stem Cell Formation in Response to the Biomechanical Forces of Blood Flow. Developmental Cell. 2020 Feb 24;52(4):446-460.e5. PMID: 32032546

Vo Lt. Kinney MA, Liu X, Zhang Y, Barragan J, Sousa PM, Jha DK, Han A, Cesana M, Shao Z, North TE, Orkin SH, Doulatov S, Xu J, and Daley GQ. Regulation of embryonic haematopoietic multipotency by EZH1. 2018. Nature 553(7689): 506-510. PMCID: PMC5785461.

Theodore LN*, Hagedorn EJ*, Cortes M*, Natsuhara KH, Liu SY, Perlin JR, Yang S, Daily ML, Zon LI and North TE. Distinct Roles for Matrix Metalloproteinase 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration and Niche Colonization. 2017. Stem Cell Reports 8(5): 1226-1241. PMCID: PMC5425629.

Kwan W, Cortes M, Frost I, Esain V, Theodore LN, Liu SY, Budrow N, Goessling W and North TE. The Central Nervous System Regulates Embryonic HSPC Production via Stress-Responsive Glucocorticoid Receptor Signaling. 2016. Cell Stem Cell 19: 1-13 (3): 370-82. PMCID: PMC5181112.



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of Harvard College