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ZFIN ID: ZDB-PERS-060712-14
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BIOGRAPHY AND RESEARCH INTERESTS
Dr. Trista E. North is an Associate Professor at Harvard Medical School (HMS) and a Principal Investigator at Children’s Hospital 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 full member of the Dana-Farber/Harvard Cancer Center. Dr. North received a Bachelor’s degree from Bowdoin College in 1996, and her PhD from Dartmouth College in 2002. Her graduate work, in the laboratory of Dr. Nancy A. Speck, examined the function of Runx1 in hematopoietic (blood) stem cell (HSC) development in murine embryos. Dr. North conducted her postdoctoral research with Dr. Leonard I. Zon at Children’s Hospital, Harvard Medical School, using zebrafish to identify novel modulators of Runx1+ HSC production via a chemical screening approach; this methodology led to the first example of FDA approval for the investigational use of a compound (Prostaglandin E2 (PGE2)) identified in zebrafish for human clinical application (umbilical cord blood transplantation). Dr. North has served on the board of Directors for the International Society of Experimental Hematology, and as the chair of the publications committee, and was the founding editor of the Simply Blood blog. She is the head of the Hematology Research Group of the Zebrafish Disease Models Society (ZDMS) and is also editorial board member and guest editor for Experimental Hematology. Dr. North was named ASH Scholar in 2010, a V Foundation Scholar in 2011, and is currently a Scholar of the Leukemia and Lymphoma Society. Dr. North was recently awarded the 2017 McCulloch and Till award for outstanding hematology research from the International Society of Experimental Hematology.
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. The North lab uses 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 life-long function. To determine conservation of regulatory effect and translational application, the North lab utilizes murine HSC development and regeneration assays, and human HSC in vitro culture and xenograft models. Ongoing work in the North laboratory 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 hematopoiesis, including relevance to hematologic disease. Together, prior and ongoing work from the North lab 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 production and/or function for use in transplantation biology.
PUBLICATIONS
Song, J., Gooding, A.R., Hemphill, W.O., Love, B.D., Robertson, A., Yao, L., Zon, L.I., North, T.E., Kasinath, V., Cech, T.R. (2023) Structural basis for inactivation of PRC2 by G-quadruplex RNA. Science (New York, N.Y.). 381:133113371331-1337
Weeks, O., Miller, B.M., Pepe-Mooney, B.J., Oderberg, I.M., Freeburg, S.H., Smith, C.J., North, T.E., Goessling, W. (2022) Embryonic alcohol exposure disrupts the ubiquitin-proteasome system. JCI insight. 7(23):
Frame, J.M., Kubaczka, C., Long, T.L., Esain, V., Soto, R.A., Hachimi, M., Jing, R., Shwartz, A., Goessling, W., Daley, G.Q., North, T.E. (2020) Metabolic Regulation of Inflammasome Activity Controls Embryonic Hematopoietic Stem and Progenitor Cell Production. Developmental Cell. 55(2):133-149.e6
Chaturantabut, S., Shwartz, A., Garnaas, M.K., LaBella, K., Li, C.C., Carroll, K.J., Cutting, C.C., Budrow, N., Palaria, A., Gorelick, D.A., Tremblay, K.D., North, T.E., Goessling, W. (2020) Estrogen acts via estrogen receptor 2b to regulate hepatobiliary fate during vertebrate development. Hepatology (Baltimore, Md.). 72(5):1786-1799
Lundin, V., Sugden, W.W., Theodore, L.N., Sousa, P.M., Han, A., Chou, S., Wrighton, P.J., Cox, A.G., Ingber, D.E., Goessling, W., Daley, G.Q., North, T.E. (2020) YAP Regulates Hematopoietic Stem Cell Formation in Response to the Biomechanical Forces of Blood Flow. Developmental Cell. 52(4):446-460.e5
Kinney, M.A., Vo, L.T., Frame, J.M., Barragan, J., Conway, A.J., Li, S., Wong, K.K., Collins, J.J., Cahan, P., North, T.E., Lauffenburger, D.A., Daley, G.Q. (2019) Author Correction: A systems biology pipeline identifies regulatory networks for stem cell engineering. Nature Biotechnology. 37:962
Kinney, M.A., Vo, L.T., Frame, J.M., Barragan, J., Conway, A.J., Li, S., Wong, K.K., Collins, J.J., Cahan, P., North, T.E., Lauffenburger, D.A., Daley, G.Q. (2019) A systems biology pipeline identifies regulatory networks for stem cell engineering. Nature Biotechnology. 37:810-818
Chaturantabut, S., Shwartz, A., Evason, K.J., Cox, A.G., Labella, K., Schepers, A.G., Yang, S., Aravena, M., Houvras, Y., Mancio-Silva, L., Romano, S., Gorelick, D.A., Cohen, D.E., Zon, L.I., Bhatia, S.N., North, T.E., Goessling, W. (2019) Estrogen Activation of G protein-coupled Estrogen Receptor 1 Regulates Phosphoinositide 3-kinase and mTOR Signaling to Promote Liver Growth in Zebrafish and Proliferation of Human Hepatocytes. Gastroenterology. 156(6):1788-1804.e13
Oo, Z.M., Illendula, A., Grembecka, J., Schmidt, C., Zhou, Y., Esain, V., Kwan, W., Frost, I., North, T.E., Rajewski, R.A., Speck, N.A., Bushweller, J.H. (2017) A tool compound targeting the core binding factor Runt domain to disrupt binding to CBFβ in leukemic cells. Leukemia & lymphoma. 59(9):2188-2200
Theodore, L.N., Hagedorn, E.J., Cortes, M., Natsuhara, K., Liu, S.Y., Perlin, J.R., Yang, S., Daily, M.L., Zon, L.I., North, T.E. (2017) Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization. Stem Cell Reports. 8(5):1226-1241
Lim, S.E., Esain, V., Kwan, W., Theodore, L.N., Cortes, M., Frost, I.M., Liu, S.Y., North, T.E. (2017) HIF1α-induced PDGFRβ signaling promotes developmental HSC production via IL-6 activation. Experimental hematology. 46:83-95.e6
Konantz, M., Alghisi, E., Müller, J.S., Lenard, A., Esain, V., Carroll, K.J., Kanz, L., North, T.E., Lengerke, C. (2016) Evi1 regulates Notch activation to induce zebrafish hematopoietic stem cell emergence. The EMBO journal. 35(21):2315-2331
Cortes, M., Chen, M.J., Stachura, D.L., Liu, S.Y., Kwan, W., Wright, F., Vo, L.T., Theodore, L.N., Esain, V., Frost, I.M., Schlaeger, T.M., Goessling, W., Daley, G.Q., North, T.E. (2016) Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production. Cell Reports. 17:458-468
Nissim, S., Weeksb, O., Talbot, J.C., Hedgepeth, J.W., Wucherpfennig, J., Schatzman-Bone, S., Swinburne, I., Cortes, M., Alexa, K., Megason, S., North, T.E., Amacher, S.L., Goessling, W. (2016) Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development. Developmental Biology. 418(1):108-23
Kwan, W., Cortes, M., Frost, I., Esain, V., Theodore, L.N., Liu, S.Y., Budrow, N., Goessling, W., North, T.E. (2016) The Central Nervous System Regulates Embryonic HSPC Production via Stress-Responsive Glucocorticoid Receptor Signaling. Cell Stem Cell. 19:370-82
Moore, F.E., Garcia, E.G., Lobbardi, R., Jain, E., Tang, Q., Moore, J.C., Cortes, M., Molodtsov, A., Kasheta, M., Luo, C.C., Garcia, A.J., Mylvaganam, R., Yoder, J.A., Blackburn, J.S., Sadreyev, R.I., Ceol, C.J., North, T.E., Langenau, D.M. (2016) Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish. The Journal of experimental medicine. 213(6):979-92
Liu, L.Y., Alexa, K., Cortes, M., Schatzman-Bone, S., Kim, A.J., Mukhopadhyay, B., Cinar, R., Kunos, G., North, T.E., Goessling, W. (2016) Cannabinoid receptor signaling regulates liver development and metabolism. Development (Cambridge, England). 143:609-22
Cortes, M., Liu, S.Y., Kwan, W., Alexa, K., Goessling, W., North, T.E. (2015) Accumulation of the Vitamin D Precursor Cholecalciferol Antagonizes Hedgehog Signaling to Impair Hemogenic Endothelium Formation. Stem Cell Reports. 5:471-9
Esain, V., Kwan, W., Carroll, K.J., Cortes, M., Liu, S.Y., Frechette, G.M., Sheward, L.M., Nissim, S., Goessling, W., North, T.E. (2015) Cannabinoid Receptor-2 Regulates Embryonic Hematopoietic Stem Cell Development via PGE2 and P-selectin Activity. Stem cells (Dayton, Ohio). 33(8):2596-612
Li, Y., Esain, V., Teng, L., Xu, J., Kwan, W., Frost, I.M., Yzaguirre, A.D., Cai, X., Cortes, M., Maijenburg, M.W., Tober, J., Dzierzak, E., Orkin, S.H., Tan, K., North, T.E., Speck, N.A. (2014) Inflammatory signaling regulates embryonic hematopoietic stem and progenitor cell production. Genes & Development. 28(23):2597-612
Carroll, K.J., Esain, V., Garnaas, M.K., Cortes, M., Dovey, M.C., Nissim, S., Frechette, G.M., Liu, S.Y., Kwan, W., Cutting, C.C., Harris, J.M., Gorelick, D.A., Halpern, M.E., Lawson, N.D., Goessling, W., North, T.E. (2014) Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche. Developmental Cell. 29:437-53
Nissim, S., Sherwood, R.I., Wucherpfennig, J., Saunders, D., Harris, J.M., Esain, V., Carroll, K.J., Frechette, G.M., Kim, A.J., Hwang, K.L., Cutting, C.C., Elledge, S., North, T.E., and Goessling, W. (2014) Prostaglandin E2 regulates liver versus pancreas cell-fate decisions and endodermal outgrowth. Developmental Cell. 28(4):423-437
Cox, A.G., Saunders, D.C., Kelsey, P.B., Conway, A.A., Tesmenitsky, Y., Marchini, J.F., Brown, K.K., Stamler, J.S., Colagiovanni, D.B., Rosenthal, G.J., Croce, K.J., North, T.E., and Goessling, W. (2014) S-Nitrosothiol Signaling Regulates Liver Development and Improves Outcome following Toxic Liver Injury. Cell Reports. 6(1):56-69
Harris, J.M., Esain, V., Frechette, G.M., Harris, L.J., Cox, A.G., Cortes, M., Garnaas, M.K., Carroll, K.J., Cutting, C.C., Khan, T., Elks, P.M., Renshaw, S.A., Dickinson, B.C., Chang, C.J., Murphy, M.P., Paw, B.H., Vander Heiden, M.G., Goessling, W., and North, T.E. (2013) Glucose metabolism impacts the spatio-temporal onset and magnitude of HSC induction in vivo. Blood. 121(13):2483-2493
Cooney, J.D., Hildick-Smith, G.J., Shafizadeh, E., McBride, P.F., Carroll, K.J., Anderson, H., Shaw, G.C., Tamplin, O.J., Branco, D.S., Dalton, A.J., Shah, D.I., Wong, C., Gallagher, P.G., Zon, L.I., North, T.E., and Paw, B.H. (2013) Teleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis. Developmental Biology. 373(2):431-441
Garnaas, M.K., Cutting, C.C., Meyers, A., Kelsey, P.B., Harris, J.M., North, T.E., and Goessling, W. (2012) Rargb regulates organ laterality in a zebrafish model of right atrial isomerism. Developmental Biology. 372(2):178-189
Leshchiner, I., Alexa, K., Kelsey, P., Adzhubei, I., Austin, C., Cooney, J., Anderson, H., King, M., Stottman, R., Ha, S., Drummond, I., Paw, B.H., North, T., Beier, D., Goessling, W., and Sunyaev, S. (2012) Mutation mapping and identification by whole genome sequencing. Genome research. 22(8):1541-1548
Shaik, S., Nucera, C., Inuzuka, H., Gao, D., Garnaas, M., Frechette, G., Harris, L., Wan, L., Fukushima, H., Husain, A., Nose, V., Fadda, G., Sadow, P.M., Goessling, W., North, T., Lawler, J., and Wei, W. (2012) SCFβ-TRCP suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2. The Journal of experimental medicine. 209(7):1289-1307
Colanesi, S., Taylor, K.L., Temperley, N.D., Lundegaard, P.R., Liu, D., North, T.E., Ishizaki, H., Kelsh, R.N., and Patton, E.E. (2012) Small molecule screening identifies targetable zebrafish pigmentation pathways. Pigment cell & melanoma research. 25(2):131-143
North, T.E., Babu, I.R., Vedder, L.M., Lord, A.M., Wishnok, J.S., Tannenbaum, S.R., Zon, L.I., and Goessling, W. (2010) PGE2-regulated wnt signaling and N-acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury. Proceedings of the National Academy of Sciences of the United States of America. 107(40):17315-17320
Dovey, M., Patton, E.E., Bowman, T., North, T., Goessling, W., Zhou, Y., and Zon, L.I. (2009) Topoisomerase II alpha is required for embryonic development and liver regeneration in zebrafish. Molecular and cellular biology. 29(13):3746-3753
North, T.E., Goessling, W., Peeters, M., Li, P., Ceol, C., Lord, A.M., Weber, G.J., Harris, J., Cutting, C.C., Huang, P., Dzierzak, E., and Zon, L.I. (2009) Hematopoietic stem cell development is dependent on blood flow. Cell. 137(4):736-748
Goessling, W., North, T.E., Loewer, S., Lord, A.M., Lee, S., Stoick-Cooper, C.L., Weidinger, G., Puder, M., Daley, G.Q., Moon, R.T., and Zon, L.I. (2009) Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell. 136(6):1136-1147
Upadhyay, G., Goessling, W., North, T.E., Xavier, R., Zon, L.I., and Yajnik, V. (2008) Molecular association between beta-catenin degradation complex and Rac guanine exchange factor DOCK4 is essential for Wnt/beta-catenin signaling. Oncogene. 27(44):5845-5855
Goessling, W., North, T.E., Lord, A.M., Ceol, C., Lee, S., Weidinger, G., Bourque, C., Strijbosch, R., Haramis, A.P., Puder, M., Clevers, H., Moon, R.T., and Zon, L.I. (2008) APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development. Developmental Biology. 320(1):161-174
North, T.E., Goessling, W., Walkley, C.R., Lengerke, C., Kopani, K.R., Lord, A.M., Weber, G.J., Bowman, T.V., Jang, I.H., Grosser, T., Fitzgerald, G.A., Daley, G.Q., Orkin, S.H., and Zon, L.I. (2007) Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature. 447(7147):1007-1011
NON-ZEBRAFISH PUBLICATIONS
