BBS Faculty Member - Trista North

Trista North

Department of Pathology
Director, BIDMC Zebrafish Core Facility


Beth Israel Deaconess Medical Center
Center for Life Sciences Building, Room 636
3 Blackfan Circle
Boston, MA 02115
Tel: 617-735-2083
Fax: 617-735-2480
Email: tnorth@bidmc.harvard.edu
Visit my lab page here.



Research Interests: hematovascular development, hematopoietic stem cell (HSC) biology, HSC transplantation

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 for the lifetime of the organism. 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 vivo chemical 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 vitro culture 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 hematopathologies and enhancing blood stem cell transplantation.



Last Update: 11/16/2016



Publications

For a complete listing of publications click here.

 


 

Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production.
Cortes M, Chen MJ, Stachura DL, Liu SY, Kwan W, Wright F, Vo LT, Theodore LN, Esain V, Frost IM, Schlaeger TM, Goessling W, Daley GQ,
North TE.
Cell Reports. 2016; 17(2):458-468.
PMID: 27705794

The Central Nervous System Regulates Embryonic HSPC Production via Stress-Responsive Glucocorticoid Receptor Signaling.
Kwan W, Cortes M, Frost I, Esain V, Theodore LN, Liu SY, Budrow N, Goessling W,
North TE.
Cell Stem Cell. 2016; 19(3):370-82.
PMID: 27424782

Cannabinoid Receptor-2 Regulates Embryonic Hematopoietic Stem Cell Development via Prostaglandin E2 and P-Selectin Activity.
Esain V, Kwan W, Carroll KJ, Cortes M, Liu SY, Frechette GM, Sheward LM, Nissim S, Goessling W,
North TE.
Stem Cells (Dayton, Ohio). 2015; 33(8):2596-612. NIHMSID: NIHMS691951
PMID: 25931248
PMCID: PMC4781665

Inflammatory signaling regulates embryonic hematopoietic stem and progenitor cell production.
Li Y, Esain V, Teng L, Xu J, Kwan W, Frost IM, Yzaguirre AD, Cai X, Cortes M, Maijenburg MW, Tober J, Dzierzak E, Orkin SH, Tan K,
North TE, Speck NA.
Genes & Development. 2014; 28(23):2597-612.
PMID: 25395663
PMCID: PMC4248291

Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche.
Carroll KJ, Esain V, Garnaas MK, Cortes M, Dovey MC, Nissim S, Frechette GM, Liu SY, Kwan W, Cutting CC, Harris JM, Gorelick DA, Halpern ME, Lawson ND, Goessling W,
North TE.
Developmental Cell. 2014; 29(4):437-53. NIHMSID: NIHMS600095
PMID: 24871948
PMCID:PMC4469361



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