Photo of Trista E. North,  PhD

Trista E. North, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-6410


trista.north@childrens.harvard.edu

Trista E. North, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Associate Professor, Pathology, Harvard Medical School
  • Associate Professor, Stem Cell Program, Dept. Hem/Onc, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The North laboratory focuses on developmental hematopoiesis (blood production) as a key to uncovering general principles of stem cell formation and function. Hematopoietic stem cells (HSCs) give rise to each of the blood lineages found in the adult organism; the programs regulating HSC development and homeostasis are highly evolutionarily conserved. Alterations in hematopoiesis can result in a variety of hematologic malignancies, including leukemia. We use chemical biology and genetic methods in zebrafish to identify and integrate pathways regulating hematopoietic niche formation, stem cell induction, and life-long function. We also seek to understand how environmental or extrinsic modifiers alter stem cell production, self-renewal and differentiation capacity. To investigate conservation of regulatory effects and translational application, we utilize murine HSC transplantation assays and human in vitro culture and xenograft models. Work in the North laboratory has relevance to the development of novel methods to produce and/or expand HSCs for therapeutic use in the treatment of blood disease.

Publications

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  • Oo ZM, Illendula A, Grembecka J, Schmidt C, Zhou Y, Esain V, Kwan W, Frost I, North TE, Rajewski RA, Speck NA, Bushweller JH. A tool compound targeting the core binding factor Runt domain to disrupt binding to CBFβ in leukemic cells. Leuk Lymphoma 2017. PubMed
  • Theodore LN, Hagedorn EJ, Cortes M, Natsuhara K, Liu SY, Perlin JR, Yang S, Daily ML, Zon LI, North TE. Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization. Stem Cell Reports 2017; 8:1226-1241. PubMed
  • Lim SE, Esain V, Kwan W, Theodore LN, Cortes M, Frost IM, Liu SY, North TE. HIF1α-induced PDGFRβ signaling promotes developmental HSC production via IL-6 activation. Exp Hematol 2016; 46:83-95.e6. PubMed
  • Kwan W, North TE. Netting Novel Regulators of Hematopoiesis and Hematologic Malignancies in Zebrafish. Curr Top Dev Biol 2017; 124:125-160. PubMed
  • North TE, Goessling W. Haematopoietic stem cells show their true colours. Nat Cell Biol 2016; 19:10-12. PubMed
  • 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. Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production. Cell Rep 2016; 17:458-468. PubMed
  • Nissim S, Weeks O, Talbot JC, Hedgepeth JW, Wucherpfennig J, Schatzman-Bone S, Swinburne I, Cortes M, Alexa K, Megason S, North TE, Amacher SL, Goessling W. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development. Dev Biol 2016; 418:108-23. PubMed
  • Konantz M, Alghisi E, Müller JS, Lenard A, Esain V, Carroll KJ, Kanz L, North TE, Lengerke C. Evi1 regulates Notch activation to induce zebrafish hematopoietic stem cell emergence. EMBO J 2016. PubMed
  • Kwan W, Cortes M, Frost I, Esain V, Theodore LN, Liu SY, Budrow N, Goessling W, North TE. The Central Nervous System Regulates Embryonic HSPC Production via Stress-Responsive Glucocorticoid Receptor Signaling. Cell Stem Cell 2016; 19:370-82. PubMed
  • Moore FE, Garcia EG, Lobbardi R, Jain E, Tang Q, Moore JC, Cortes M, Molodtsov A, Kasheta M, Luo CC, Garcia AJ, Mylvaganam R, Yoder JA, Blackburn JS, Sadreyev RI, Ceol CJ, North TE, Langenau DM. Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish. J Exp Med 2016; 213:979-92. PubMed
  • Goessling W, North TE. EnaBILEing Growth in the Fetal Liver. Cell Stem Cell 2016; 18:427-8. PubMed
  • Kanz D, Konantz M, Alghisi E, North TE, Lengerke C. Endothelial-to-hematopoietic transition: Notch-ing vessels into blood. Ann N Y Acad Sci 2016. PubMed
  • Liu LY, Alexa K, Cortes M, Schatzman-Bone S, Kim AJ, Mukhopadhyay B, Cinar R, Kunos G, North TE, Goessling W. Cannabinoid receptor signaling regulates liver development and metabolism. Development 2016; 143:609-22. PubMed
  • Esain V, Cortes M, North TE. Enumerating Hematopoietic Stem and Progenitor Cells in Zebrafish Embryos. Methods Mol Biol 2016; 1451:191-206. PubMed
  • Cortes M, Liu SY, Kwan W, Alexa K, Goessling W, North TE. Accumulation of the Vitamin D Precursor Cholecalciferol Antagonizes Hedgehog Signaling to Impair Hemogenic Endothelium Formation. Stem Cell Reports 2015. PubMed
  • Esain V, Kwan W, Carroll KJ, Cortes M, Liu SY, Frechette GM, Sheward LM, Nissim S, Goessling W, North TE. Cannabinoid Receptor-2 Regulates Embryonic Hematopoietic Stem Cell Development via Prostaglandin E2 and P-Selectin Activity. Stem Cells 2015; 33:2596-612. PubMed
  • 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. Inflammatory signaling regulates embryonic hematopoietic stem and progenitor cell production. Genes Dev 2014; 28:2597-612. PubMed
  • Carroll KJ, North TE. Oceans of opportunity: exploring vertebrate hematopoiesis in zebrafish. Exp Hematol 2014. PubMed
  • 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. Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche. Dev Cell 2014; 29:437-53. PubMed
  • Nissim S, Sherwood RI, Wucherpfennig J, Saunders D, Harris JM, Esain V, Carroll KJ, Frechette GM, Kim AJ, Hwang KL, Cutting CC, Elledge S, North TE, Goessling W. Prostaglandin E2 regulates liver versus pancreas cell-fate decisions and endodermal outgrowth. Dev Cell 2014; 28:423-37. PubMed
  • Cutler C, Multani P, Robbins D, Kim HT, Le T, Hoggatt J, Pelus LM, Desponts C, Chen YB, Rezner B, Armand P, Koreth J, Glotzbecker B, Ho VT, Alyea E, Isom M, Kao G, Armant M, Silberstein L, Hu P, Soiffer RJ, Scadden DT, Ritz J, Goessling W, North TE, Mendlein J, Ballen K, Zon LI, Antin JH, Shoemaker DD. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood 2013; 122:3074-81. PubMed
  • Liu LY, Fox CS, North TE, Goessling W. Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development. Dis Model Mech 2013; 6:1271-8. PubMed
  • Shan J, Schwartz RE, Ross NT, Logan DJ, Thomas D, Duncan SA, North TE, Goessling W, Carpenter AE, Bhatia SN. Identification of small molecules for human hepatocyte expansion and iPS differentiation. Nat Chem Biol 2013; 9:514-20. PubMed
  • Harris JM, Esain V, Frechette GM, Harris LJ, Cox AG, Cortes M, Garnaas MK, Carroll KJ, Cutting CC, Khan T, Elks PM, Renshaw SA, Dickinson BC, Chang CJ, Murphy MP, Paw BH, Vander Heiden MG, Goessling W, North TE. Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo. Blood 2013; 121:2483-93. PubMed
  • Cooney JD, Hildick-Smith GJ, Shafizadeh E, McBride PF, Carroll KJ, Anderson H, Shaw GC, Tamplin OJ, Branco DS, Dalton AJ, Shah DI, Wong C, Gallagher PG, Zon LI, North TE, Paw BH. Teleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis. Dev Biol 2012. PubMed
  • Garnaas MK, Cutting CC, Meyers A, Kelsey PB, Harris JM, North TE, Goessling W. Rargb regulates organ laterality in a zebrafish model of right atrial isomerism. Dev Biol 2012; 372:178-89. PubMed
  • Leshchiner I, Alexa K, Kelsey P, Adzhubei I, Austin-Tse CA, Cooney JD, Anderson H, King MJ, Stottmann RW, Garnaas MK, Ha S, Drummond IA, Paw BH, North TE, Beier DR, Goessling W, Sunyaev SR. Mutation mapping and identification by whole-genome sequencing. Genome Res 2012; 22:1541-8. PubMed
  • 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 human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models. Cell Stem Cell 2011; 8:445-58. PubMed
  • North TE, Babu IR, Vedder LM, Lord AM, Wishnok JS, Tannenbaum SR, Zon LI, Goessling W. PGE2-regulated wnt signaling and N-acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury. Proc Natl Acad Sci U S A 2010; 107:17315-20. PubMed
  • Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z, Zon LI, Armstrong SA. The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science 2010; 327:1650-3. PubMed
  • North TE, Goessling W. Previews. NOTCHing an arrow at cord blood: translating stem cell knowledge into clinical practice. Cell Stem Cell 2010; 6:186-7. PubMed
  • North TE,Goessling W,Peeters M,Li P,Ceol C,Lord AM,Weber GJ,Harris J,Cutting CC,Huang P,Dzierzak E,Zon LI. Hematopoietic stem cell development is dependent on blood flow. Cell 2009; 137:736-48. PubMed
  • Goessling W,North TE,Loewer S,Lord AM,Lee S,Stoick-Cooper CL,Weidinger G,Puder M,Daley GQ,Moon RT,Zon LI. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 2009; 136:1136-47. PubMed
  • Goessling W, North TE, Lord AM, Ceol C, Lee S, Weidinger G, Bourque C, Strijbosch R, Haramis AP, Puder M, Clevers H, Moon RT, Zon LI. APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development. Dev Biol 2008; 320:161-74. PubMed
  • North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord AM, Weber GJ, Bowman TV, Jang IH, Grosser T, Fitzgerald GA, Daley GQ, Orkin SH, Zon LI. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 2007; 447:1007-11. PubMed
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