Photo of David M. Langenau,  PhD

David M. Langenau, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 643-6508


dlangenau@mgh.harvard.edu

David M. Langenau, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Pathology, Harvard Medical School
  • Associate Chair for Research, Pathology, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Langenau laboratory research focus is to uncover the mechanisms driving progression and relapse in pediatric tumors. Using novel, transgenic zebrafish models of pediatric sarcoma and leukemia that mimic human malignancy, we have undertaken studies to discover novel therapies by addition of drugs to the water and imaging tumor growth in live zebrafish. Moreover, we have utilized detailed imaging studies to visualize tumor cells in live animals and assess how cellular heterogeneity drives continued tumor growth. Capitalizing on insights gained from our zebrafish models of cancer, we are now extending our findings to human T-cell acute lymphoblastic leukemia and rhabdomyosarcoma.

Publications

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  • Yan C, Yang Q, Do D, Brunson DC, Langenau DM. Adult immune compromised zebrafish for xenograft cell transplantation studies. EBioMedicine 2019; 47:24-26. PubMed
  • Yohe ME, Heske CM, Stewart E, Adamson PC, Ahmed N, Antonescu CR, Chen E, Collins N, Ehrlich A, Galindo RL, Gryder BE, Hahn H, Hammond S, Hatley ME, Hawkins DS, Hayes MN, Hayes-Jordan A, Helman LJ, Hettmer S, Ignatius MS, Keller C, Khan J, Kirsch DG, Linardic CM, Lupo PJ, Rota R, Shern JF, Shipley J, Sindiri S, Tapscott SJ, Vakoc CR, Wexler LH, Langenau DM. Insights into pediatric rhabdomyosarcoma research: Challenges and goals. Pediatr Blood Cancer 2019. PubMed
  • Yan C, Brunson DC, Tang Q, Do D, Iftimia NA, Moore JC, Hayes MN, Welker AM, Garcia EG, Dubash TD, Hong X, Drapkin BJ, Myers DT, Phat S, Volorio A, Marvin DL, Ligorio M, Dershowitz L, McCarthy KM, Karabacak MN, Fletcher JA, Sgroi DC, Iafrate JA, Maheswaran S, Dyson NJ, Haber DA, Rawls JF, Langenau DM. Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish. Cell 2019; 177:1903-1914.e14. PubMed
  • Osseiran S, Austin LA, Cannon TM, Yan C, Langenau DM, Evans CL. Longitudinal monitoring of cancer cell subpopulations in monolayers, 3D spheroids, and xenografts using the photoconvertible dye DiR. Sci Rep 2019; 9:5713. PubMed
  • Chen H, Albergante L, Hsu JY, Lareau CA, Lo Bosco G, Guan J, Zhou S, Gorban AN, Bauer DE, Aryee MJ, Langenau DM, Zinovyev A, Buenrostro JD, Yuan GC, Pinello L. Single-cell trajectories reconstruction, exploration and mapping of omics data with STREAM. Nat Commun 2019; 10:1903. PubMed
  • Borga C, Foster CA, Iyer S, Garcia SP, Langenau DM, Frazer JK. Molecularly distinct models of zebrafish Myc-induced B cell leukemia. Leukemia 2018. PubMed
  • Garcia EG, Iyer S, Garcia SP, Loontiens S, Sadreyev RI, Speleman F, Langenau DM. Cell of origin dictates aggression and stem cell number in acute lymphoblastic leukemia. Leukemia 2018. PubMed
  • Hayes MN, McCarthy K, Jin A, Oliveira ML, Iyer S, Garcia SP, Sindiri S, Gryder B, Motala Z, Nielsen GP, Borg JP, van de Rijn M, Malkin D, Khan J, Ignatius MS, Langenau DM. Vangl2/RhoA Signaling Pathway Regulates Stem Cell Self-Renewal Programs and Growth in Rhabdomyosarcoma. Cell Stem Cell 2018; 22:414-427.e6. PubMed
  • Lobbardi R, Pinder J, Martinez-Pastor B, Theodorou M, Blackburn JS, Abraham BJ, Namiki Y, Mansour M, Abdelfattah NS, Molodtsov A, Alexe G, Toiber D, de Waard M, Jain E, Boukhali M, Lion M, Bhere D, Shah K, Gutierrez A, Stegmaier K, Silverman LB, Sadreyev RI, Asara JM, Oettinger MA, Haas W, Look AT, Young RA, Mostoslavsky R, Dellaire G, Langenau DM. TOX regulates growth, DNA repair, and genomic instability in T-cell Acute Lymphoblastic Leukemia. 2017. PubMed
  • Tang Q, Iyer S, Lobbardi R, Moore JC, Chen H, Lareau C, Hebert C, Shaw ML, Neftel C, Suva ML, Ceol CJ, Bernards A, Aryee M, Pinello L, Drummond IA, Langenau DM. Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing. J Exp Med 2017; 214:2875-2887. PubMed
  • Ignatius MS, Hayes MN, Lobbardi R, Chen EY, McCarthy KM, Sreenivas P, Motala Z, Durbin AD, Molodtsov A, Reeder S, Jin A, Sindiri S, Beleyea BC, Bhere D, Alexander MS, Shah K, Keller C, Linardic CM, Nielsen PG, Malkin D, Khan J, Langenau DM. The NOTCH1/SNAIL1/MEF2C Pathway Regulates Growth and Self-Renewal in Embryonal Rhabdomyosarcoma. Cell Rep 2017; 19:2304-2318. PubMed
  • Tenente IM, Hayes MN, Ignatius MS, McCarthy K, Yohe M, Sindiri S, Gryder B, Oliveira ML, Ramakrishnan A, Tang Q, Chen EY, Petur Nielsen G, Khan J, Langenau DM. Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma. Elife 2017. PubMed
  • Moore JC, Tang Q, Yordán NT, Moore FE, Garcia EG, Lobbardi R, Ramakrishnan A, Marvin DL, Anselmo A, Sadreyev RI, Langenau DM. Single-cell imaging of normal and malignant cell engraftment into optically clear prkdc-null SCID zebrafish. J Exp Med 2016; 213:2575-2589. 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
  • Tang Q, Moore JC, Ignatius MS, Tenente IM, Hayes MN, Garcia EG, Torres Yordán N, Bourque C, He S, Blackburn JS, Look AT, Houvras Y, Langenau DM. Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish. Nat Commun 2016; 7:10358. PubMed
  • Tang Q, Abdelfattah NS, Blackburn JS, Moore JC, Martinez SA, Moore FE, Lobbardi R, Tenente IM, Ignatius MS, Berman JN, Liwski RS, Houvras Y, Langenau DM. Optimized cell transplantation using adult rag2 mutant zebrafish. Nat Methods 2014. PubMed
  • Blackburn JS, Liu S, Wilder JL, Dobrinski KP, Lobbardi R, Moore FE, Martinez SA, Chen EY, Lee C, Langenau DM. Clonal evolution enhances leukemia-propagating cell frequency in T cell acute lymphoblastic leukemia through Akt/mTORC1 pathway activation. Cancer Cell 2014; 25:366-78. PubMed
  • Ignatius MS, Chen E, Elpek NM, Fuller AZ, Tenente IM, Clagg R, Liu S, Blackburn JS, Linardic CM, Rosenberg AE, Nielsen PG, Mempel TR, Langenau DM. In vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma. Cancer Cell 2012; 21:680-93. PubMed
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