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Ryan O'Connell

Professor of Microbiology and Immunology

Noncoding RNAs, Inflammation, Cancer, Extracellular Vesicles, Microbiota and Metabolism

 

Ryan O'Connell

 

Molecular Biology Program

Education

B.S. California Lutheran University

Ph.D. University of California, Los Angeles

Links

Lab Page

PubMed Literature Search

ryan.oconnell@path.utah.edu

 

Research

I am a Professor in the Department of Pathology at the University of Utah, and my laboratory is located at the Huntsman Cancer Institute. My postdoctoral studies were performed in Dr. David Baltimore’s laboratory at the California Institute of Technology where I began working in the area of microRNAs (miRNAs) following my graduate training in Immunology at UCLA. My research program has since been focused on studying the roles of miRNAs in regulating both physiological and pathological immune cell functions in mammals, with an emphasis on inflammation and cancer.

The lab is currently focused on the following:

  • Understanding the communication between the mammalian host and gut microbiota via extracellular vesicles and their RNA cargo during inflammatory bowel disease (IBD) and colorectal cancer (CRC).
  • Exploring the role of miRNAs in coordinating antitumor and immuno therapeutic responses to gastrointestinal (GI) and blood cancers.
  • The development and mechanistic study of mRNA vaccines to induce immunity against GI and blood cancers.
  • Defining the interplay between miRNAs and cellular metabolism during age-related inflammation (GI and muscle) and cancer (GI).

Collectively, my work as a trainee and as an independent principal investigator has resulted in the publication of over 100 high impact primary research manuscripts and review articles, and has significantly contributed to our current understanding of the importance of microRNAs during the development, function and transformation of hematopoietic cells. Furthermore, I also serve in multiple leadership roles at the University of Utah that include Co-Director of the Immunology, Inflammation and Infectious Disease (3i) Initiative, Associate Chief of the Microbiology and Immunology Division, and Program Co-Director of the Neuroimmunology Training Grant. Of note, I have mentored 14 graduate students (4 MD/PhD students) and 6 postdoctoral scholars, many of whom have advanced to exciting positions in academia and industry.

References

  1. Bauer KM, Nelson MC, Tang WW, Chiaro TR, Brown DG, Ghazaryan A., Lee S-H, Allison M. Weis AM, Hill JH, Klag KA, Tran VT, Thompson JW, Ramstead AG, Monts JK, Marvin JE, Alexander M, Voth WP, Stephens WZ, Ward DM, Petrey AC, Round JL* and O’Connell RM.* CD11c+ myeloid cell exosomes reduce intestinal inflammation during colitis. JCI Insight 2022, Oct 10;7(19):e159469. PMCID: PMC9675566.
  2. Ost KS, O'Meara TR, Stephens WZ, Chiaro T, Zhou H, Penman J, Bell R, Catanzaro JR, Song D, Singh S, Call DH, Hwang-Wong E, Hanson KE, Valentine JF, Christensen KA, O'Connell RM, Cormack B, Ibrahim AS, Palm NW, Noble SM, Round JL. Adaptive immunity induces mutualism between commensal eukaryotes. Nature. 2021 Aug;596(7870):114-118.
  3. Huffaker TB, Ekiz HA, Barba C, Lee S-H, Runtsch MC, Nelson MC, Bauer KM, Tang WW, Mosbruger TL, Cox JE, Round JL, Voth WP, O’Connell RM. A Stat1 bound enhancer promotes Nampt expression and function within tumor associated macrophages. Nature Communications, 2021 May 11. 12;2620. PMCID: PMC8113251.
  4. Fix DK, Ekiz HA, Petrocelli JJ, Mckenzie AM, Mahmassani ZS, O'Connell RM, Drummond MJ. Disrupted macrophage metabolic reprogramming in aged soleus muscle during early recovery following disuse atrophy. Aging Cell. 2021 Sep;20(9):e13448.
  5. Stephens WZ, Kubinak JL, Ghazaryan A, Bauer KM, Bell R, Buhrke K, Chiaro TR, Weis AM, Tang WW, Monts JK, Soto R, Ekiz HA, O'Connell RM*, Round JL*. Epithelial-myeloid exchange of MHC class II constrains immunity and microbiota composition. Cell Rep. 2021 Nov 2;37(5):109916.
  6. Warner, LM, Dong, J, Lin, L-L, Chen, M-C, O’Connell, RM, and Lu, L-F (2020). Thymic epithelial miR-155 promotes regulatory T cell development by safeguarding medullary thymic epithelial cell maturation. J. Exp. Med. Feb 1;218(2):e20192423.
  7. Ekiz, HA, Conley, CJ, Stephens, WZ and O'Connell, RM (2020). CIPR: a web-based R/shiny app and R package to annotate cell clusters in single cell RNA sequencing experiments. BMC Bioinformatics, May 15;21(1):191.
  8. Ramstead AG, Wallace JA, Lee S-H, Bauer KM, Tang WW, Ekiz HA, Cluntun AA, Bettini ML, Round JL, Rutter J, O’Connell RM (2020). Mitochondrial Pyruvate Carrier 1 (MPC1) promotes peripheral T cell homeostasis through metabolic regulation of thymic development. Cell Reports, 2020 Mar 3;30(9):2889-2899.
  9. Reidy PT, McKenzie AI, Mahmassani ZS, Petrocelli JJ, Nelson DB, Lindsay CC, Gardner JE, Morrow VR, Keefe AC, Huffaker TB, Stoddard GJ, Kardon G, O'Connell RM, Drummond MJ. Aging impairs mouse skeletal muscle macrophage polarization and muscle-specific abundance during recovery from disuse. Am J Physiol Endocrinol Metab. 2019 Jul 1;317(1):E85-E98
  10. Runtsch MC, Nelson MC, Lee SH, Voth W, Alexander M, Hu R, Wallace J, Petersen C, Panic V, Villanueva CJ, Evason KJ, Bauer KM, Mosbruger T, Boudina S, Bronner M, Round JL, Drummond MJ, O'Connell RM. Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease. PLoS Genet. 2019 Feb 15;15(2):e1007970.
  11. Ekiz HA, Huffaker TB, Grossmann AH, Stephens WZ, Williams MA, Round JL, O'Connell RM. MicroRNA-155 coordinates the immunological landscape within murine melanoma and correlates with immunity in human cancers. JCI Insight. 2019 Mar 21;4(6). pii: 126543. doi: 10.1172/jci.insight.126543
  12. Alexander M, Ramstead AG, Bauer KM, Lee SH, Runtsch MC, Wallace J, Huffaker TB, Larsen DK, Tolmachova T, Seabra MC, Round JL, Ward DM, O'Connell RM. Rab27-Dependent Exosome Production Inhibits Chronic Inflammation and Enables Acute Responses to Inflammatory Stimuli. J Immunol. 2017 Nov 15;199(10):3559-3570.
  13. Huffaker TB, Lee SH, Tang WW, Wallace JA, Alexander M, Runtsch MC, Larsen DK, Thompson J, Ramstead AG, Voth WP, Hu R, Round JL, Williams MA, O'Connell RM Antitumor immunity is defective in T cell-specific microRNA-155-deficient mice and is rescued by immune checkpoint blockade. J Biol Chem. 2017 Nov 10;292(45):18530-18541.
  14. Wallace JA, O'Connell RM. MicroRNAs and acute myeloid leukemia: therapeutic implications and emerging concepts. Blood. 2017 Sep 14;130(11):1290-1301.
  15. Soto R, Petersen C, Novis CL, Kubinak JL, Bell R, Stephens WZ, Lane TE, Fujinami RS, Bosque A, O'Connell RM, Round JL. Microbiota promotes systemic T cell survival through suppression of an apoptotic factor. Proc Natl Acad Sci. 2017 May 23;114(21):5497-5502.
  16. Wallace JA, Kagele DA, Eiring AM, Kim CN, Hu R, Runtsch MC, Alexander M, Huffaker TB, Lee SH, Patel AB, Mosbruger TL, Voth W, Rao DS, Miles RR, Round JL, Deininger MW, O'Connell RM. miR-155 promotes FLT3-ITD-induced myeloproliferative disease through inhibition of the interferon response. Blood. 2017 Jun 8;129(23):3074-3086.
  17. Chiaro T, Soto R, Stephens, WZ, Kubinak, JL, Petersen, C, Gogokhia L, Bell R, Delgado JC, Cox J, Voth W, Brown J, Stillman D, O’Connell RM, Tebo A and Round JL. A member of the mycobiota modulates host metabolism to increase intestinal permeability and disease. Science Translational Medicine. 2017 Mar 8;9(380).
  18. Dickey L, Worne C, Glover J, Lane T and O’Connell RM. MicroRNA-155 enhances T cell trafficking and antiviral effector function in a model of coronavirus-induced neurologic disease. Journal of Neuroinflammation. 2016 Sep 7;13(1):240.
  19. Wallace J, Hu R, Mosbruger TL, Dahlem TJ, Stephens WZ, Rao DS, Round JL, O'Connell RM. Genome-Wide CRISPR-Cas9 Screen Identifies MicroRNAs That Regulate Myeloid Leukemia Cell Growth. PLoS One. 2016 Apr 15;11(4):e0153689.
  20. Kubinak JL, Stephens WZ, Soto R, Petersen C, Chiaro T, Gogokhia L, Bell R, Ajami NJ, Petrosino JF, Morrison L, Potts WK, Jensen PE, O'Connell RM, Round JL. MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection. Nat Commun. 2015 Oct 23;6:8642.
  21. Runtsch MC, Hu R, Alexander M, Wallace J, Kagele D, Petersen C, Valentine JF, Welker NC, Bronner MP, Chen X, Smith DP, Ajami NJ, Petrosino JF, Round JL, O'Connell RM. MicroRNA-146a constrains multiple parameters of intestinal immunity and increases susceptibility to DSS colitis. Oncotarget. 2015 Oct 6;6(30):28556-72.
  22. Alexander M, O'Connell RM. Noncoding RNAs and chronic inflammation: Micro-managing the fire within. Bioessays. 2015 Sep;37(9):1005-15. Review.
  23. Huffaker TB, O'Connell RM. miR-155-SOCS1 as a Functional Axis: Satisfying the Burden of Proof. Immunity. 2015 Jul 21;43(1):3-4.
  24. Alexander M, Hu R, Runtsch MC, Kagele DA, Mosbruger TL, Tolmachova T, Seabra MC, Round JL, Ward DM, O'Connell RM. Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat Commun. 2015 Jun 18;6:7321.
  25. O'Connell RM. Endogenous miR-29a regulates HSC function in mammals. Blood. 2015 Apr 2;125(14):2180-1.
  26. Kubinak JL, Petersen C, Stephens WZ, Soto R, Bake E, O'Connell RM, Round JL.  MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health. Cell Host Microbe. 2015 Feb 11;17(2):153-63.
  27. Hu R, Kagele DA, Huffaker TB, Runtsch MC, Alexander M, Liu J, Bake E, Su W, Williams MA, Rao DS, Möller T, Garden GA, Round JL, O'Connell RM. miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation. Immunity. 2014 Oct 16;41(4):605-19.
  28. Lochhead RB, Ma Y, Zachary JF, Baltimore D, Zhao JL, Weis JH, O'Connell RM, Weis JJ. MicroRNA-146a provides feedback regulation of lyme arthritis but not carditis during infection with Borrelia burgdorferi. PLoS Pathog. 2014 Jun 26;10(6):e1004212.
  29. Zhao JL, Ma C, O'Connell RM, Mehta A, DiLoreto R, Heath JR, Baltimore D. Conversion of danger signals into cytokine signals by hematopoietic stem and progenitor cells for regulation of stress-induced hematopoiesis. Cell Stem Cell. 2014 Apr 3;14(4):445-59.
  30. Zhao JL, Rao DS, O'Connell RM, Garcia-Flores Y, Baltimore D. MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice. Elife. 2013 May 21;2:e00537.
  31. Hu R, Huffaker TB, Kagele DA, Runtsch MC, Bake E, Chaudhuri AA, Round JL, O'Connell RM. MicroRNA-155 Confers Encephalogenic Potential to Th17 Cells by Promoting Effector Gene Expression. J Immunol. 2013 Jun 15;190(12):5972-80.
  32. Hu R, Wallace J, Dahlem TJ, Grunwald DJ, O'Connell RM. Targeting human microRNA genes using engineered Tal-effector nucleases (TALENs). PLoS One. 2013 May 7;8(5):e63074.
  33. Hu R, O'Connell RM. MicroRNA control in the development of systemic autoimmunity. Arthritis Res Ther. 2013 Jan 25;15(1):202.
  34. Huffaker TB, Hu R, Runtsch MC, Bake E, Chen X, Zhao J, Round JL, Baltimore D, O'Connell RM. Epistasis between microRNAs 155 and 146a during T cell-mediated antitumor immunity. Cell Rep. 2012 Dec 27;2(6):1697-709.
  35. Hu R, O'Connell RM. MiR-23b is a safeguard against autoimmunity. Nat Med. 2012 Jul 6;18(7):1009-10.
  36. O'Connell RM. MicroRNAs function on a new level. Blood. 2012 Apr 26;119(17):3875-6.
  37. Chaudhuri AA, So AY, Mehta A, Minisandram A, Sinha N, Jonsson VD, Rao DS, O'Connell RM, Baltimore D. Oncomir miR-125b regulates hematopoiesis by targeting the gene Lin28A. Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4233-8.
  38. O'Connell RM, Baltimore D. MicroRNAs and hematopoietic cell development. Curr Top Dev Biol. 2012;99:145-74.
  39. O'Connell RM, Rao DS, Baltimore D. microRNA regulation of inflammatory responses. Annu Rev Immunol. 2012;30:295-312.
  40. Chaudhuri AA, So AY, Sinha N, Gibson WS, Taganov KD, O'Connell RM, Baltimore D. MicroRNA-125b potentiates macrophage activation. J Immunol. 2011 Nov 15;187(10):5062-8.
  41. O'Connell RM, Zhao JL, Rao DS. MicroRNA function in myeloid biology. Blood. 2011 Sep 15;118(11):2960-9.
  42. Zhao JL, Rao DS, Boldin MP, Taganov KD, O'Connell RM, Baltimore D. NF-kappaB dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies. Proc Natl Acad Sci U S A. 2011 May 31;108(22):9184-9.
  43. Pietras EM, Miller LS, Johnson CT, O'Connell RM, Dempsey PW, Cheng G. A MyD88-dependent IFNγR-CCR2 signaling circuit is required for mobilization of monocytes and host defense against systemic bacterial challenge. Cell Res. 2011 Jul;21(7):1068-79.
  44. O'Connell RM, Kahn D, Gibson WS, Round JL, Scholz RL, Chaudhuri AA, Kahn ME, Rao DS, Baltimore D. MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity. 2010 Oct 29;33(4):607-19.
  45. O'Connell RM, Chaudhuri AA, Rao DS, Gibson WS, Balazs AB, Baltimore D. MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14235-40.
  46. Rao DS, O'Connell RM, Chaudhuri AA, Garcia-Flores Y, Geiger TL, Baltimore D. MicroRNA-34a perturbs B lymphocyte development by repressing the forkhead box transcription factor Foxp1. Immunity. 2010 Jul 23;33(1):48-59.
  47. O'Connell RM, Balazs AB, Rao DS, Kivork C, Yang L, Baltimore D. Lentiviral vector delivery of human interleukin-7 (hIL-7) to human immune system (HIS) mice expands T lymphocyte populations. PLoS One. 2010 Aug 6;5(8):e12009.
  48. O'Connell RM, Chaudhuri AA, Rao DS, Baltimore D. Inositol phosphatase SHIP1 is a primary target of miR-155. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7113-8.
  49. Hwang S, Kim KS, Flano E, Wu TT, Tong LM, Park AN, Song MJ, Sanchez DJ, O'Connell RM, Cheng G, Sun R. Conserved herpesviral kinase promotes viral persistence by inhibiting the IRF-3-mediated type I interferon response. Cell Host Microbe. 2009 Feb 19;5(2):166-78.
  50. Luo XM, Maarschalk E, O'Connell RM, Wang P, Yang L, Baltimore D. Engineering human hematopoietic stem/progenitor cells to produce a broadly neutralizing anti-HIV antibody after in vitro maturation to human B lymphocytes. Blood. 2009 Feb 12;113(7):1422-31.
  51. O'Connell RM, Rao DS, Chaudhuri AA, Boldin MP, Taganov KD, Nicoll J, Paquette RL, Baltimore D. Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J Exp Med. 2008 Mar 17;205(3):585-94.
Last Updated: 8/11/23