ZFIN ID: ZDB-PERS-020717-10
Langenau, David
Email: dlangenau@partners.org
URL: http://langenaulab.com
Affiliation: Langenau Lab
Address: Assistant Professor of Pathology Principal Investigator Harvard Stem Cell Institute Harvard Medical School Massachusetts General Hospital 149 13th Street Charlestown, MA 02129 USA
Country: United States
Phone: 617-643-6508
Fax:
Orcid ID:


BIOGRAPHY AND RESEARCH INTERESTS
Our laboratory uses transgenic zebrafish models of rabdomyosarcoma to uncover the mechanisms by which a subset of malignant cells, the cancer stem cell, can remake tumor.

Using fluorescent transgenic zebrafish and cutting-edge live cell imaging, we are now visualizing ERMS development in real-time. Moreover, our fluorescent transgenic approaches allow for the identification of malignant cell sub-types and should afford unprecedented opportunities to visualize self-renewal within a tumor directly. Using conditional transgenic approaches and chemical genetics, we are currently interrogating which pathways modulate self-renewal, cancer stem cell number, and tumor growth in ERMS. Uncovering downstream molecular pathways that regulate self-renewal will be integral to identifying novel drugs for the treatment of this disease.


PUBLICATIONS
Ignatius, M.S., Hayes, M.N., Moore, F.E., Tang, Q., Garcia, S.P., Blackburn, P.R., Baxi, K., Wang, L., Jin, A., Ramakrishnan, A., Reeder, S., Chen, Y., Nielsen, G.P., Chen, E.Y., Hasserjian, R.P., Tirode, F., Ekker, S.C., Langenau, D.M. (2018) tp53 deficiency causes a wide tumor spectrum and increases embryonal rhabdomyosarcoma metastasis in zebrafish.. eLIFE. 7:
Mansour, M.R., He, S., Li, Z., Lobbardi, R., Abraham, B.J., Hug, C., Rahman, S., Leon, T.E., Kuang, Y.Y., Zimmerman, M.W., Blonquist, T., Gjini, E., Gutierrez, A., Tang, Q., Garcia-Perez, L., Pike-Overzet, K., Anders, L., Berezovskaya, A., Zhou, Y., Zon, L.I., Neuberg, D., Fielding, A.K., Staal, F.J.T., Langenau, D.M., Sanda, T., Young, R.A., Look, A.T. (2018) JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia. The Journal of experimental medicine. 215(7):1929-1945
Hayes, M.N., McCarthy, K., Jin, A., Oliveira, M.L., Iyer, S., Garcia, S.P., Sindiri, S., Gryder, B., Motala, Z., Nielsen, G.P., Borg, J.P., van de Rijn, M., Malkin, D., Khan, J., Ignatius, M.S., Langenau, D.M. (2018) Vangl2/RhoA Signaling Pathway Regulates Stem Cell Self-Renewal Programs and Growth in Rhabdomyosarcoma. Cell Stem Cell. 22:414-427.e6
Lobbardi, R., Pinder, J., Martinez-Pastor, B., Theodorou, M., Blackburn, J.S., Abraham, B.J., Namiki, Y., Mansour, M., Abdelfattah, N.S., Molodtsov, A., Alexe, G., Toiber, D., de Waard, M., Jain, E., Boukhali, M., Lion, M., Bhere, D., Shah, K., Gutierrez, A., Stegmaier, K., Silverman, L.B., Sadreyev, R.I., Asara, J.M., Oettinger, M.A., Haas, W., Look, A.T., Young, R.A., Mostoslavsky, R., Dellaire, G., Langenau, D.M. (2017) TOX regulates growth, DNA repair, and genomic instability in T-cell Acute Lymphoblastic Leukemia. Cancer discovery. 7(11):1336-1353
Kasheta, M., Painter, C.A., Moore, F.E., Lobbardi, R., Bryll, A., Freiman, E., Stachura, D., Rogers, A.B., Houvras, Y., Langenau, D.M., Ceol, C.J. (2017) Identification and characterization of T reg-like cells in zebrafish. The Journal of experimental medicine. 214(12):3519-3530
Tang, Q., Iyer, S., Lobbardi, R., Moore, J.C., Chen, H., Lareau, C., Hebert, C., Shaw, M.L., Neftel, C., Suva, M.L., Ceol, C.J., Bernards, A., Aryee, M., Pinello, L., Drummond, I.A., Langenau, D.M. (2017) Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing. The Journal of experimental medicine. 214(10):2875-2887
Fazio, M., Avagyan, S., van Rooijen, E., Mannherz, W., Kaufman, C.K., Lobbardi, R., Langenau, D.M., Zon, L.I. (2017) Efficient Transduction of Zebrafish Melanoma Cell Lines and Embryos Using Lentiviral Vectors. Zebrafish. 14(4):379-382
Bharathy, N., Svalina, M.N., Settelmeyer, T.P., Cleary, M.M., Berlow, N.E., Airhart, S.D., Xiang, S., Keck, J., Hayden, J.B., Shern, J.F., Mansoor, A., Lathara, M., Srinivasa, G., Langenau, D.M., Keller, C. (2017) Preclinical testing of the glycogen synthase kinase-3β inhibitor tideglusib for rhabdomyosarcoma. Oncotarget. 8:62976-62983
Ignatius, M.S., Hayes, M.N., Lobbardi, R., Chen, E.Y., McCarthy, K.M., Sreenivas, P., Motala, Z., Durbin, A.D., Molodtsov, A., Reeder, S., Jin, A., Sindiri, S., Beleyea, B.C., Bhere, D., Alexander, M.S., Shah, K., Keller, C., Linardic, C.M., Nielsen, P.G., Malkin, D., Khan, J., Langenau, D.M. (2017) The NOTCH1/SNAIL1/MEF2C Pathway Regulates Growth and Self-Renewal in Embryonal Rhabdomyosarcoma. Cell Reports. 19:2304-2318
Berberoglu, M.A., Gallagher, T.L., Morrow, Z.T., Talbot, J.C., Hromowyk, K.J., Tenente, I.M., Langenau, D.M., Amacher, S.L. (2017) Satellite-like cells contribute to pax7-dependent skeletal muscle repair in adult zebrafish. Developmental Biology. 424(2):162-180
Tenente, I.M., Hayes, M.N., Ignatius, M.S., McCarthy, K., Yohe, M., Sindiri, S., Gryder, B., Oliveira, M.L., Ramakrishnan, A., Tang, Q., Chen, E.Y., Petur Nielsen, G., Khan, J., Langenau, D.M. (2017) Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma. eLIFE. 6
Hayes, M.N., Langenau, D.M. (2017) Discovering novel oncogenic pathways and new therapies using zebrafish models of sarcoma. Methods in cell biology. 138:525-561
Moore, J.C., Mulligan, T.S., Torres Yordán, N., Castranova, D., Pham, V.N., Tang, Q., Lobbardi, R., Anselmo, A., Liwski, R.S., Berman, J.N., Sadreyev, R.I., Weinstein, B.M., Langenau, D.M. (2016) T cell immune deficiency in zap70 mutant zebrafish. Molecular and cellular biology. 36(23):2868-2876
Moore, J.C., Tang, Q., Yordán, N.T., Moore, F.E., Garcia, E.G., Lobbardi, R., Ramakrishnan, A., Marvin, D.L., Anselmo, A., Sadreyev, R.I., Langenau, D.M. (2016) Single-cell imaging of normal and malignant cell engraftment into optically clear prkdc-null SCID zebrafish. The Journal of experimental medicine. 213(12):2575-2589
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
Au, S.H., Storey, B.D., Moore, J.C., Tang, Q., Chen, Y.L., Javaid, S., Sarioglu, A.F., Sullivan, R., Madden, M.W., O'Keefe, R., Haber, D.A., Maheswaran, S., Langenau, D.M., Stott, S.L., Toner, M. (2016) Clusters of circulating tumor cells traverse capillary-sized vessels. Proceedings of the National Academy of Sciences of the United States of America. 113(18):4947-52
Tang, Q., Moore, J.C., Ignatius, M.S., Tenente, I.M., Hayes, M.N., Garcia, E.G., Torres Yordán, N., Bourque, C., He, S., Blackburn, J.S., Look, A.T., Houvras, Y., Langenau, D.M. (2016) Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish. Nature communications. 7:10358
Moore, J.C., Langenau, D.M. (2016) Allograft Cancer Cell Transplantation in Zebrafish. Advances in experimental medicine and biology. 916:265-87
Ignatius, M.S., Hayes, M., Langenau, D.M. (2016) In Vivo Imaging of Cancer in Zebrafish. Advances in experimental medicine and biology. 916:219-37
Tenente, I.M., Tang, Q., Moore, J.C., Langenau, D.M. (2014) Normal and Malignant Muscle Cell Transplantation into Immune Compromised Adult Zebrafish. Journal of visualized experiments : JoVE. (94)
Tang, Q., Abdelfattah, N.S., Blackburn, J.S., Moore, J.C., Martinez, S.A., Moore, F.E., Lobbardi, R., Tenente, I.M., Ignatius, M.S., Berman, J.N., Liwski, R.S., Houvras, Y., Langenau, D.M. (2014) Optimized cell transplantation using adult rag2 mutant zebrafish. Nature Methods. 11(8):821-4
Blackburn, J.S., Langenau, D.M. (2014) Zebrafish as a model to assess cancer heterogeneity, progression and relapse. Disease models & mechanisms. 7:755-762
Gutierrez, A., Feng, H., Stevenson, K., Neuberg, D.S., Calzada, O., Zhou, Y., Langenau, D.M., Look, A.T. (2014) Loss of function tp53 mutations do not accelerate the onset of myc-induced T-cell acute lymphoblastic leukaemia in the zebrafish. British journal of haematology. 166(1):84-90
Chen, E.Y., Deran, M.T., Ignatius, M.S., Grandinetti, K.B., Clagg, R., McCarthy, K.M., Lobbardi, R.M., Brockmann, J., Keller, C., Wu, X., Langenau, D.M. (2014) Glycogen synthase kinase 3 inhibitors induce the canonical WNT/β-catenin pathway to suppress growth and self-renewal in embryonal rhabdomyosarcoma. Proc. Natl. Acad. Sci. USA. 111(14):5349-54
Blackburn, J.S., Liu, S., Wilder, J.L., Dobrinski, K.P., Lobbardi, R., Moore, F.E., Martinez, S.A., Chen, E.Y., Lee, C., Langenau, D.M. (2014) Clonal evolution enhances leukemia-propagating cell frequency in T cell acute lymphoblastic leukemia through Akt/mTORC1 pathway activation. Cancer Cell. 25:366-78
Langenau, D.M. (2014) Pten regulates zebrafish hematopoiesis. Blood. 123(2):149-150
Chen, E.Y., Dobrinski, K.P., Brown, K.H., Clagg, R., Edelman, E., Ignatius, M.S., Chen, J.Y., Brockmann, J., Nielsen, G.P., Ramaswamy, S., Keller, C., Lee, C., and Langenau, D.M. (2013) Cross-species array comparative genomic hybridization identifies novel oncogenic events in zebrafish and human embryonal rhabdomyosarcoma. PLoS Genetics. 9(8):e1003727
Storer, N.Y., White, R.M., Uong, A., Price, E., Nielsen, G.P., Langenau, D.M., and Zon, L.I. (2013) Zebrafish rhabdomyosarcoma reflects the developmental stage of oncogene expression during myogenesis. Development (Cambridge, England). 140(14):3040-3050
Le, X., Pugach, E.K., Hettmer, S., Storer, N.Y., Liu, J., Wills, A.A., Dibiase, A., Chen, E.Y., Ignatius, M.S., Poss, K.D., Wagers, A.J., Langenau, D.M., and Zon, L.I. (2013) A novel chemical screening strategy in zebrafish identifies common pathways in embryogenesis and rhabdomyosarcoma development. Development (Cambridge, England). 140(11):2354-64
Albacker, C.E., Storer, N.Y., Langdon, E.M., Dibiase, A., Zhou, Y., Langenau, D.M., and Zon, L.I. (2013) The Histone Methyltransferase SUV39H1 Suppresses Embryonal Rhabdomyosarcoma Formation in Zebrafish. PLoS One. 8(5):e64969
Blackburn, J.S., Liu, S., Raiser, D.M., Martinez, S.A., Feng, H., Meeker, N.D., Gentry, J., Neuberg, D., Look, A.T., Ramaswamy, S., Bernards, A., Trede, N.S., and Langenau, D.M. (2012) Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency. Leukemia. 26(9):2069-2078
Ignatius, M.S., Chen, E., Elpek, N.M., Fuller, A.Z., Tenente, I.M., Clagg, R., Liu, S., Blackburn, J.S., Linardic, C.M., Rosenberg, A.E., Nielsen, P.G., Mempel, T.R., and Langenau, D.M. (2012) In Vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma. Cancer Cell. 21(5):680-693
Moore, F.E., and Langenau, D.M. (2012) Through the Looking Glass: Visualizing Leukemia Growth, Migration, and Engraftment Using Fluorescent Transgenic Zebrafish. Advances in hematology. 2012:478164
Moore, F.E., Reyon, D., Sander, J.D., Martinez, S.A., Blackburn, J.S., Khayter, C., Ramirez, C.L., Joung, J.K., and Langenau, D.M. (2012) Improved Somatic Mutagenesis in Zebrafish Using Transcription Activator-Like Effector Nucleases (TALENs). PLoS One. 7(5):e37877
Blackburn, J.S., Liu, S., and Langenau, D.M. (2011) Quantifying the Frequency of Tumor-propagating Cells Using Limiting Dilution Cell Transplantation in Syngeneic Zebrafish. Journal of visualized experiments : JoVE. (53):e2790
Blackburn, J.S., Liu, S., Raimondi, A.R., Ignatius, M.S., Salthouse, C.D., and Langenau, D.M. (2011) High-throughput imaging of adult fluorescent zebrafish with an LED fluorescence macroscope. Nature Protocols. 6(2):229-241
Sander, J.D., Dahlborg, E.J., Goodwin, M.J., Cade, L., Zhang, F., Cifuentes, D., Curtin, S.J., Blackburn, J.S., Thibodeau-Beganny, S., Qi, Y., Pierick, C.J., Hoffman, E., Maeder, M.L., Khayter, C., Reyon, D., Dobbs, D., Langenau, D.M., Stupar, R.M., Giraldez, A.J., Voytas, D.F., Peterson, R.T., Yeh, J.R., Joung, J.K. (2011) Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nature Methods. 8:67-9
Ignatius, M.S., and Langenau, D.M. (2011) Fluorescent imaging of cancer in zebrafish. Meth. Cell. Biol.. 105:437-459
Chen, E.Y., and Langenau, D.M. (2011) Zebrafish models of rhabdomyosarcoma. Meth. Cell. Biol.. 105:383-402
Feng, H., Stachura, D.L., White, R.M., Gutierrez, A., Zhang, L., Sanda, T., Jette, C.A., Testa, J.R., Neuberg, D.S., Langenau, D.M., Kutok, J.L., Zon, L.I., Traver, D., Fleming, M.D., Kanki, J.P., and Look, A.T. (2010) T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. Cancer Cell. 18(4):353-366
Smith, A.C., Raimondi, A.R., Salthouse, C.D., Ignatius, M.S., Blackburn, J.S., Mizgirev, I.V., Storer, N.Y., de Jong, J.L., Chen, A.T., Zhou, Y., Revskoy, S., Zon, L.I., and Langenau, D.M. (2010) High-throughput cell transplantation establishes that tumor-initiating cells are abundant in zebrafish T-cell acute lymphoblastic leukemia. Blood. 115(16):3296-3303
Blackburn, J.S., and Langenau, D.M. (2010) aMAZe-ing tools for mosaic analysis in zebrafish. Nature Methods. 7(3):188-190
Ignatius, M.S., and Langenau, D.M. (2009) Zebrafish as a Model for Cancer Self-Renewal. Zebrafish. 6(4):377-387
Freeman, J.L., Ceol, C., Feng, H., Langenau, D.M., Belair, C., Stern, H.M., Song, A., Paw, B.H., Look, A.T., Zhou, Y., Zon, L.I., and Lee, C. (2009) Construction and application of a zebrafish array comparative genomic hybridization platform. Genes, chromosomes & cancer. 48(2):155-170
Langenau, D.M., Keefe, M.D., Storer, N.Y., Jette, C.A., Smith, A.C., Ceol, C.J., Bourque, C., Look, A.T., and Zon, L.I. (2008) Co-injection strategies to modify radiation sensitivity and tumor initiation in transgenic Zebrafish. Oncogene. 27(30):4242-4248
Jette, C.A., Flanagan, A.M., Ryan, J., Pyati, U.J., Carbonneau, S., Stewart, R.A., Langenau, D.M., Look, A.T., and Letai, A. (2008) BIM and other BCL-2 family proteins exhibit cross-species conservation of function between zebrafish and mammals. Cell death and differentiation. 15(6):1063-1072
Burket, C.T., Montgomery, J.E., Thummel, R., Kassen, S.C., Lafave, M.C., Langenau, D.M., Zon, L.I., and Hyde, D.R. (2008) Generation and characterization of transgenic zebrafish lines using different ubiquitous promoters. Transgenic Research. 17(2):265-279
Feng, H., Langenau, D.M., Madge, J.A., Quinkertz, A., Gutierrez, A., Neuberg, D.S., Kanki, J.P., and Look, A.T. (2007) Heat-shock induction of T-cell lymphoma/leukaemia in conditional Cre/lox-regulated transgenic zebrafish. British journal of haematology. 138(2):169-175
Langenau, D.M., Keefe, M.D., Storer, N.Y., Guyon, J.R., Kutok, J.L., Le, X., Goessling, W., Neuberg, D.S., Kunkel, L.M., and Zon, L.I. (2007) Effects of RAS on the genesis of embryonal rhabdomyosarcoma. Genes and Development. 21(11):1382-1395
Le, X., Langenau, D.M., Keefe, M.D., Kutok, J.L., Neuberg, D.S., and Zon, L.I. (2007) Heat shock-inducible Cre/Lox approaches to induce diverse types of tumors and hyperplasia in transgenic zebrafish. Proc. Natl. Acad. Sci. USA. 104(22):9410-9415
Berghmans, S., Jette, C., Langenau, D., Hsu, K., Stewart, R., Look, T., and Kanki, J.P. (2005) Making waves in cancer research: new models in the zebrafish. Biotechniques. 39(2):227-237
Langenau, D.M., Feng, H., Berghmans, S., Kanki, J.P., Kutok, J.L., and Look, A.T. (2005) Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. USA. 102(17):6068-6073
Langenau, D.M., Jette, C., Berghmans, S., Palomero, T., Kanki, J.P., Kutok, J.L., and Look, A.T. (2005) Suppression of apoptosis by bcl-2-overexpression in lymphoid cells of transgenic zebrafish. Blood. 105(8):3278-3285
Langenau, D.M., and Zon, L.I. (2005) The zebrafish: a new model of T-cell and thymic development. Nature reviews. Immunology. 5(4):307-17
Traver, D., Winzeler, A., Stern, H.M., Mayhall, E.A., Langenau, D.M., Kutok, J.L., Look, A.T., and Zon, L.I. (2004) Effects of lethal irradiation in zebrafish and rescue by hematopoietic cell transplantation. Blood. 104(5):1298-1305
Langenau, D.M., Ferrando, A.A., Traver, D., Kutok, J.L., Hezel, J.P., Kanki, J.P., Zon, L.I., Look, A.T., and Trede, N.S. (2004) In vivo tracking of T cell development, ablation, and engraftment in transgenic zebrafish. Proc. Natl. Acad. Sci. USA. 101(19):7369-7374
Trede, N.S., Langenau, D.M., Traver, D., Look, A.T., and Zon, L.I. (2004) The use of zebrafish to understand immunity. Immunity. 20(4):367-379
Langenau, D.M. (2004) Transgenic models of T-cell acute lymphoblastic leukemia in the zebrafish. Ph.D. Thesis. :188p
Liu, T.X., Howlett, N.G., Deng, M., Langenau, D.M., Hsu, K., Rhodes, J., Kanki, J.P., D'Andrea, A.D., and Look, A.T. (2003) Knockdown of zebrafish fancd2 causes developmental abnormalities via p53-dependent apoptosis. Developmental Cell. 5(6):903-914
Langenau, D.M., Traver, D., Ferrando, A.A., Kutok, J.L., Aster, J.C., Kanki, J.P., Lin, S., Prochownik, E., Trede, N.S., Zon, L.I., and Look, A.T. (2003) Myc-induced T cell leukemia in transgenic zebrafish. Science (New York, N.Y.). 299(5608):887-890
Langenau, D., Palomero, T., Kanki, J., Ferrando, A., Zhou, Y., Zon, L., and Look, A. (2002) Molecular cloning and developmental expression of Tlx (Hox11) genes in zebrafish (Danio rerio). Mechanisms of Development. 117(1-2):243-248
Bennett, C.M., Kanki, J.P., Rhodes, J., Liu, T.X., Paw, B.H., Kieran, M.W., Langenau, D.M., Delahaye-Brown, A., Zon, L.I., Fleming, M.D., and Look, A.T. (2001) Myelopoiesis in the zebrafish, Danio rerio. Blood. 98(3):643-651
Bennett, C.M., Fleming, M.D., Kanki, J.P., Rhodes, J., Delahaye-Brown, A., Langenau, D.M., Liu, T.X., Paw, B.H., Zon, L.I., and Look, A.T. (2000) Genetic analysis of myelopoiesis the zebrafish. Blood. 96(11):4177
Bauer, M.P., Bridgham, J.T., Langenau, D.M., Johnson, A.L., and Goetz, F.W (2000) Conservation of steroidogenic acute regulatory (StAR) protein structure and expression in vertebrates. Molecular and Cellular Endocrinology. 168(1-2):119-125

NON-ZEBRAFISH PUBLICATIONS