Trista E.. North, Ph.D.
Harvard Medical School
Director, BIDMC Zebrafish Core Facility
Beth Israel Deaconess Medical Center
Harvard Medical School
330 Brookline Avenue, E/CLS-636
Boston, MA 02215
Dr. Trista E. North is an Associate Professor at Harvard Medical School (HMS) and Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts, USA. She is Principal Faculty at the Harvard Stem Cell Institute (HSCI) and a Developmental and Regererative Biology (DRB) faculty member in the Biological and Biomedical Sciences (BBS) Graduate Program at HMS. Dr. North is a member of the BIDMC Cancer Center and Center for Vascular Biology. 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; this line of investigation revealed a conserved regulatory role for Prostaglandin E2 and Nitric Oxide in HSC production, which has therapeutic application. Dr. North started her own laboratory at BIDMC/HMS in 2008 and is the director of the BIDMC Zebrafish Core Facility. Dr. North 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. Research in the North laboratory has been generously funded by the National Institutes of Health (NIH), the Leukemia and Lymphoma Society, the American Society of Hematology, the V Foundation and the HSCI.
Research Interests: Hematovascular Development, Hematopoietic Stem Cell (HSC) Biology, HSC Transplantation
Basic Research - 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.
New and Noteworthy Publications:
Lim SE, Esain V, Kwan W, Theodore LN, Cortes M, Frost IM, Liu SY, North TE. . HIF1?-induced PDGFR? signaling promotes developmental HSC production via IL-6 activation. Experimental Hematology. 2016; (in press). PMID: 27751871 .
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 Reports. 2016; 17(2):458-468. PMID: 27705794 .
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(3):370-82. PMID: 27424782 .
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. The Journal of Experimental Medicine. 2016; 213(6):979-92. PMID: 27139488. PMCID: PMC4886368 .
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. The Journal of Experimental Medicine. 2016; 213(6):979-92. PMID: 27139488. PMCID: PMC4886368 .
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 (Dayton, Ohio). 2015; 33(8):2596-612. NIHMSID: NIHMS691951. PMID: 25931248. PMCID: PMC4781665 .