ABOUT THE RESEARCHER

OVERVIEW

RNA is an ancient and universal biopolymer that is involved in nearly every aspect of biology. Next to nucleic acids, proteins, and lipids, glycans are the fourth fundamental biopolymer. Glycans perform a myriad of essential functions, especially in the context of cell surface events, where complex glycans facilitate the folding and purposeful trafficking of proteins and lipids for secretion or membrane presentation. Processes such as embryogenesis, host-pathogen recognition, and tumor-immune interactions rely on proper glycosylation. Interestingly while glycans, lipids, and proteins all work together in these highly conserved processes, nucleic acids have been traditionally excluded. However, our most recent work has led to the discovery that some RNAs are glycosylated with complex N-glycans. This new class of biomolecule, glycoRNA, represents a physical link between the world of RNA and that of glycosylation. Flynn Lab is focused on exploring the interface of two key biomolecules, RNA and glycans, by developing and implementing chemical, biochemical, and genetic tools. Understanding the regulatory mechanisms underlying glycoRNA and the interface of the secretory pathway and nucleic acids will have implications for the basic biology of processes such as stem cells, cancer, and regeneration. Researcher Background Ryan Flynn is an Assistant Professor at the Boston Children’s Hospital in the Stem Cell Program and in the Department of Stem Cell and Regenerative Biology at Harvard University. Ryan graduated from MIT in 2010 and subsequently completed his M.D. and Ph.D. training at Stanford University in 2017. After completing his postdoctoral fellowship also at Stanford, he moved to Harvard to establish his independent laboratory in 2021.

PUBLICATIONS

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  1. The CD22-IGF2R interaction is a therapeutic target for microglial lysosome dysfunction in Niemann-Pick type C. Sci Transl Med. 2021 Dec; 13(622):eabg2919. View abstract
  2. Diverse functional elements in RNA predicted transcriptome-wide by orthogonal RNA structure probing. Nucleic Acids Res. 2021 11 18; 49(20):11868-11882. View abstract
  3. fSHAPE, fSHAPE-eCLIP, and SHAPE-eCLIP probe transcript regions that interact with specific proteins. STAR Protoc. 2021 Sep 17; 2(3):100762. View abstract
  4. Small RNAs are modified with N-glycans and displayed on the surface of living cells. Cell. 2021 06 10; 184(12):3109-3124.e22. View abstract
  5. Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021 04 29; 184(9):2394-2411.e16. View abstract
  6. Progenitor identification and SARS-CoV-2 infection in human distal lung organoids. Nature. 2020 12; 588(7839):670-675. View abstract
  7. Proteomic analysis of young and old mouse hematopoietic stem cells and their progenitors reveals post-transcriptional regulation in stem cells. Elife. 2020 11 25; 9. View abstract
  8. Footprinting SHAPE-eCLIP Reveals Transcriptome-wide Hydrogen Bonds at RNA-Protein Interfaces. Mol Cell. 2020 12 03; 80(5):903-914.e8. View abstract
  9. Systematic discovery and functional interrogation of SARS-CoV-2 viral RNA-host protein interactions during infection. bioRxiv. 2020 Oct 06. View abstract
  10. A memory of eS25 loss drives resistance phenotypes. Nucleic Acids Res. 2020 07 27; 48(13):7279-7297. View abstract
  11. Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures. bioRxiv. 2020 Jul 27. View abstract
  12. RNA helicase DDX21 mediates nucleotide stress responses in neural crest and melanoma cells. Nat Cell Biol. 2020 04; 22(4):372-379. View abstract
  13. DNA-PKcs has KU-dependent function in rRNA processing and haematopoiesis. Nature. 2020 03; 579(7798):291-296. View abstract
  14. Inhibition of inositol kinase B controls acute and chronic graft-versus-host disease. Blood. 2020 01 02; 135(1):28-40. View abstract
  15. Functional significance of U2AF1 S34F mutations in lung adenocarcinomas. Nat Commun. 2019 12 13; 10(1):5712. View abstract
  16. An RNA-centric dissection of host complexes controlling flavivirus infection. Nat Microbiol. 2019 12; 4(12):2369-2382. View abstract
  17. Activated protein C ameliorates chronic graft-versus-host disease by PAR1-dependent biased cell signaling on T cells. Blood. 2019 08 29; 134(9):776-781. View abstract
  18. HiChIRP reveals RNA-associated chromosome conformation. Nat Methods. 2019 06; 16(6):489-492. View abstract
  19. Targeting PI3Kd function for amelioration of murine chronic graft-versus-host disease. Am J Transplant. 2019 06; 19(6):1820-1830. View abstract
  20. The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders. Elife. 2019 01 10; 8. View abstract
  21. C5aR1 regulates T follicular helper differentiation and chronic graft-versus-host disease bronchiolitis obliterans. JCI Insight. 2018 12 20; 3(24). View abstract
  22. Small-molecule BCL6 inhibitor effectively treats mice with nonsclerodermatous chronic graft-versus-host disease. Blood. 2019 01 03; 133(1):94-99. View abstract
  23. Retraction Note: DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. Nature. 2018 10; 562(7725):150. View abstract
  24. Notch signaling mediated by Delta-like ligands 1 and 4 controls the pathogenesis of chronic GVHD in mice. Blood. 2018 11 15; 132(20):2188-2200. View abstract
  25. Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders. Nature. 2018 02 01; 554(7690):112-117. View abstract
  26. Murine chronic graft-versus-host disease proteome profiling discovers CCL15 as a novel biomarker in patients. Blood. 2018 04 12; 131(15):1743-1754. View abstract
  27. Inhibition of NGLY1 Inactivates the Transcription Factor Nrf1 and Potentiates Proteasome Inhibitor Cytotoxicity. ACS Cent Sci. 2017 Nov 22; 3(11):1143-1155. View abstract
  28. Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements. Nat Genet. 2017 Nov; 49(11):1602-1612. View abstract
  29. An activated Th17-prone T cell subset involved in chronic graft-versus-host disease sensitive to pharmacological inhibition. JCI Insight. 2017 Jun 15; 2(12). View abstract
  30. The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity. Cell. 2017 Jun 01; 169(6):1051-1065.e18. View abstract
  31. Invariant natural killer T cells ameliorate murine chronic GVHD by expanding donor regulatory T cells. Blood. 2017 06 08; 129(23):3121-3125. View abstract
  32. Comparative Analysis Reveals Furoyl in Vivo Selective Hydroxyl Acylation Analyzed by Primer Extension Reagents Form Stable Ribosyl Ester Adducts. Biochemistry. 2017 Apr 04; 56(13):1811-1814. View abstract
  33. Comparison of SHAPE reagents for mapping RNA structures inside living cells. RNA. 2017 02; 23(2):169-174. View abstract
  34. Novel Gene Expression Profile of Women with Intrinsic Skin Youthfulness by Whole Transcriptome Sequencing. PLoS One. 2016; 11(11):e0165913. View abstract
  35. An inducible long noncoding RNA amplifies DNA damage signaling. Nat Genet. 2016 11; 48(11):1370-1376. View abstract
  36. HiChIP: efficient and sensitive analysis of protein-directed genome architecture. Nat Methods. 2016 Nov; 13(11):919-922. View abstract
  37. ROCK2 signaling is required to induce a subset of T follicular helper cells through opposing effects on STATs in autoimmune settings. Sci Signal. 2016 07 19; 9(437):ra73. View abstract
  38. Isoform-specific targeting of ROCK proteins in immune cells. Small GTPases. 2016 07 02; 7(3):173-7. View abstract
  39. RNA Duplex Map in Living Cells Reveals Higher-Order Transcriptome Structure. Cell. 2016 May 19; 165(5):1267-1279. View abstract
  40. Medulloblastoma-associated DDX3 variant selectively alters the translational response to stress. Oncotarget. 2016 May 10; 7(19):28169-82. View abstract
  41. Proteomics analysis reveals a Th17-prone cell population in presymptomatic graft-versus-host disease. JCI Insight. 2016 May 05; 1(6). View abstract
  42. irCLIP platform for efficient characterization of protein-RNA interactions. Nat Methods. 2016 06; 13(6):489-92. View abstract
  43. Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma. Mol Cell. 2016 Apr 07; 62(1):34-46. View abstract
  44. Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism. Blood. 2016 04 28; 127(17):2144-54. View abstract
  45. 7SK-BAF axis controls pervasive transcription at enhancers. Nat Struct Mol Biol. 2016 Mar; 23(3):231-8. View abstract
  46. Corrigendum: DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. Nature. 2016 May 05; 533(7601):130. View abstract
  47. Transcriptome-wide interrogation of RNA secondary structure in living cells with icSHAPE. Nat Protoc. 2016 Feb; 11(2):273-90. View abstract
  48. DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. Nature. 2015 Dec 24; 528(7583):517-22. View abstract
  49. Transcriptome analysis of GVHD reveals aurora kinase A as a targetable pathway for disease prevention. Sci Transl Med. 2015 Nov 25; 7(315):315ra191. View abstract
  50. Leukemia-Associated Cohesin Mutants Dominantly Enforce Stem Cell Programs and Impair Human Hematopoietic Progenitor Differentiation. Cell Stem Cell. 2015 Dec 03; 17(6):675-688. View abstract
  51. Erratum: Structural imprints in vivo decode RNA regulatory mechanisms. Nature. 2015 Nov 12; 527(7577):264. View abstract
  52. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015 Oct; 29(10):2062-8. View abstract
  53. Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells. Nature. 2015 Jun 11; 522(7555):221-5. View abstract
  54. Targeting Syk-activated B cells in murine and human chronic graft-versus-host disease. Blood. 2015 Jun 25; 125(26):4085-94. View abstract
  55. Systematic discovery of Xist RNA binding proteins. Cell. 2015 Apr 09; 161(2):404-16. View abstract
  56. B7-H3 expression in donor T cells and host cells negatively regulates acute graft-versus-host disease lethality. Blood. 2015 05 21; 125(21):3335-46. View abstract
  57. Structural imprints in vivo decode RNA regulatory mechanisms. Nature. 2015 Mar 26; 519(7544):486-90. View abstract
  58. Strategies to inhibit alloantibody production in alloprimed murine recipients of hematopoietic stem cell grafts. Am J Transplant. 2015 Apr; 15(4):931-41. View abstract
  59. RNA helicase DDX21 coordinates transcription and ribosomal RNA processing. Nature. 2015 Feb 12; 518(7538):249-53. View abstract
  60. Dissecting noncoding and pathogen RNA-protein interactomes. RNA. 2015 Jan; 21(1):135-43. View abstract
  61. Therapeutic activity of multiple common ?-chain cytokine inhibition in acute and chronic GVHD. Blood. 2015 Jan 15; 125(3):570-80. View abstract
  62. m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell. 2014 Dec 04; 15(6):707-19. View abstract
  63. Ibrutinib treatment ameliorates murine chronic graft-versus-host disease. J Clin Invest. 2014 Nov; 124(11):4867-76. View abstract
  64. CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease. J Clin Invest. 2014 Oct; 124(10):4266-80. View abstract
  65. RNA structural analysis by evolving SHAPE chemistry. Wiley Interdiscip Rev RNA. 2014 Nov-Dec; 5(6):867-81. View abstract
  66. Long noncoding RNAs in cell-fate programming and reprogramming. Cell Stem Cell. 2014 Jun 05; 14(6):752-61. View abstract
  67. Abstract 158: Identification of BMP-Responsive Long Noncoding RNAs in Pluripotent Cells. Plast Reconstr Surg. 2014 Mar; 133(3 Suppl):174. View abstract
  68. Essential role of lncRNA binding for WDR5 maintenance of active chromatin and embryonic stem cell pluripotency. Elife. 2014 Feb 12; 3:e02046. View abstract
  69. Landscape and variation of RNA secondary structure across the human transcriptome. Nature. 2014 Jan 30; 505(7485):706-9. View abstract
  70. The seed and the soil: optimizing stem cells and their environment for tissue regeneration. Ann Plast Surg. 2013 Feb; 70(2):235-9. View abstract
  71. Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature. 2013 Jan 10; 493(7431):231-5. View abstract
  72. RNA SHAPE analysis in living cells. Nat Chem Biol. 2013 Jan; 9(1):18-20. View abstract
  73. Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers. Genome Biol. 2012 Aug 28; 13(8):R75. View abstract
  74. Contrasting acute graft-versus-host disease effects of Tim-3/galectin-9 pathway blockade dependent upon the presence of donor regulatory T cells. Blood. 2012 Jul 19; 120(3):682-90. View abstract
  75. SU-E-T-606: Optimal Emission Angle Selection in Rotating Shield Brachytherapy. Med Phys. 2012 Jun; 39(6Part19):3845. View abstract
  76. SU-E-T-547: Rotating Shield Brachytherapy (RSBT) for Cervical Cancer. Med Phys. 2012 Jun; 39(6Part18):3831. View abstract
  77. Active chromatin and noncoding RNAs: an intimate relationship. Curr Opin Genet Dev. 2012 Apr; 22(2):172-8. View abstract
  78. Donor B-cell alloantibody deposition and germinal center formation are required for the development of murine chronic GVHD and bronchiolitis obliterans. Blood. 2012 Feb 09; 119(6):1570-80. View abstract
  79. Antisense RNA polymerase II divergent transcripts are P-TEFb dependent and substrates for the RNA exosome. Proc Natl Acad Sci U S A. 2011 Jun 28; 108(26):10460-5. View abstract
  80. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011 Apr 07; 472(7341):120-4. View abstract
  81. Construction of a novel expression cassette for increasing transgene expression in vivo in endothelial cells of large blood vessels. Gene Ther. 2011 May; 18(5):501-8. View abstract
  82. A unique chromatin signature uncovers early developmental enhancers in humans. Nature. 2011 Feb 10; 470(7333):279-83. View abstract
  83. Phosphotyrosine signaling analysis of site-specific mutations on EGFRvIII identifies determinants governing glioblastoma cell growth. Mol Biosyst. 2010 Jul; 6(7):1227-37. View abstract
  84. c-Myc regulates transcriptional pause release. Cell. 2010 Apr 30; 141(3):432-45. View abstract
  85. Divergent transcription from active promoters. Science. 2008 Dec 19; 322(5909):1849-51. View abstract
  86. Quantitative analysis of EGFRvIII cellular signaling networks reveals a combinatorial therapeutic strategy for glioblastoma. Proc Natl Acad Sci U S A. 2007 Jul 31; 104(31):12867-72. View abstract
  87. Diagnosis, treatment, and management of breast cancer in previously augmented women. Breast J. 2006 Jul-Aug; 12(4):343-8. View abstract
  88. Components of high-level vision: a cognitive neuroscience analysis and accounts of neurological syndromes. Cognition. 1990 Mar; 34(3):203-77. View abstract