Ryan O'Connell, PhD

Associate Chief, Division of Microbiology and Immunology

Research Interests

  • Metabolism
  • Secretory Vesicles
  • Immunology
  • T Cell Biology
  • Tumor Microenvironment
  • Autoimmune Diseases
  • RNA, Small Interfering
  • Acute Myeloid Leukemia (AML)
  • Inflammation
  • Cellular Immunology, Macrophage Functions

Labs

Lab Website

Languages

  • English

Academic Information

  • Departments: Pathology - Associate Professor
  • Divisions: Microbiology and Immunology
  • Cancer Center Programs: Nuclear Control of Cell Growth & Differentiation

Academic Office Information

  • 801-213-4153
  • Huntsman Cancer Institute
    Microbiology and Immunology - Dept. of Pathology
    2000 Circle of Hope, Room: Rm 5245
    Salt Lake City, UT 84112

Email: ryan.oconnell@path.utah.edu

Academic Bio

I am currently an Associate Professor at the University of Utah in the Department of Pathology. My postdoctoral studies were performed in David Baltimore’s laboratory at the California Institute of Technology where I began working in the area of microRNAs following my graduate training in Immunology at UCLA (mentored by Genhong Cheng). My research has since been focused on studying the roles of microRNAs in regulating both physiological and pathological hematopoietic development in mammals, with a focus on inflammation and cancer. My work, which has led to the publication of many high impact primary research manuscripts and several review articles on this topic, has contributed to our current understanding of how microRNAs influence the development and function of immune cells. Since moving to the University of Utah in August of 2011, I have established an independent research program in the Division of Microbiology and Immunology (within the Department of Pathology) and am currently an investigator at the Huntsman Cancer Institute. We are working towards a greater understanding of how noncoding RNAs regulate inflammatory responses, with an emphasis on pathways that are relevant to human disease including cancer.

Education History

Type School Degree
Postdoctoral Fellowship California Institute of Technology
Molecular Immunology
Postdoctoral Scholar
Postdoctoral Fellowship University of California at Los Angeles
Laboratory of Genhong Cheng
Postdoctoral Fellow
Doctoral Training University of California, Los Angeles
Microbiology, Immunology and Molecular Genetics
Ph.D.
Graduate Training University of the Pacific
Biology
M.S.
Undergraduate California Lutheran University
Biology
B.S.

Selected Publications

Journal Article

  1. Petersen C, Bell R, Klag KA, Lee SH, Soto R, Ghazaryan A, Buhrke K, Ekiz HA, Ost KS, Boudina S, OConnell RM, Cox JE, Villanueva CJ, Stephens WZ, Round JL (2018). T cell-mediated regulation of the microbiota protects against obesity. Science, 365(6451).
  2. Brown DG, Soto R, Yandamuri S, Stone C, Dickey L, Gomes-Neto JC, Pastuzyn ED, Bell R, Petersen C, Buhrke K, Fujinami RS, OConnell RM, Stephens WZ, Shepherd JD, Lane TE, Round JL (2019). The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling. eLife, 8.
  3. Ekiz HA, Huffaker TB, Grossmann AH, Stephens WZ, Williams MA, Round JL, OConnell RM (2019). MicroRNA-155 coordinates the immunological landscape within murine melanoma and correlates with immunity in human cancers. JCI Insight, 4(6).
  4. 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, OConnell RM (2019). Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease. PLoS Genet, 15(2), e1007970.
  5. Gogokhia L, Burhke K, Bell R, Hoffman B, Brown DG, Hanke-Gogokhia C, Ajami NJ, Wong MC, Ghazaryan A, Valentine JF, Porter N, Martens E, OConnell RM, Jacob V, Scherl E, Crawford C, Stephens WZ, Casjens SR, Longman RS, Round JL (2019). Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis. Cell Host Microbe, 25(2), 285-299.
  6. Alexander M, Ramstead AG, Bauer KM, Lee SH, Runtsch MC, Wallace J, Huffaker TB, Larsen DK, Tolmachova T, Seabra MC, Round JL, Ward DM, OConnell RM (2017). Rab27-Dependent Exosome Production Inhibits Chronic Inflammation and Enables Acute Responses to Inflammatory Stimuli. J Immunol, 199(10), 3559-3570.
  7. 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, OConnell RM (2017). Antitumor immunity is defective in T cell-specific microRNA-155-deficient mice and is rescued by immune checkpoint blockade. J Biol Chem, 292(45), 18530-18541.
  8. Wallace JA, Kagele DA, Eiring AM, Kim CN, Hu R, Runtsch MC, Alexander M, Huffaker TB, Lee SH, Patel AB, Mosbruger TL, Voth WP, Rao DS, Miles RR, Round JL, Deininger MW, OConnell RM (2017). miR-155 promotes FLT3-ITD-induced myeloproliferative disease through inhibition of the interferon response. Blood, 129(23), 3074-3086.
  9. Chiaro TR, Soto R, Zac Stephens W, Kubinak JL, Petersen C, Gogokhia L, Bell R, Delgado JC, Cox J, Voth W, Brown J, Stillman DJ, OConnell RM, Tebo AE, Round JL (2017). A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice. Sci Transl Med, 9(380).
  10. Dickey LL, Worne CL, Glover JL, Lane TE, OConnell RM (2016). MicroRNA-155 enhances T cell trafficking and antiviral effector function in a model of coronavirus-induced neurologic disease. J Neuroinflammation, 13(1), 240.
  11. Wallace J, Hu R, Mosbruger TL, Dahlem TJ, Stephens WZ, Rao DS, Round JL, OConnell RM (2016). Genome-Wide CRISPR-Cas9 Screen Identifies MicroRNAs That Regulate Myeloid Leukemia Cell Growth. PLoS ONE, 11(4), e0153689.
  12. Kubinak JL, Stephens WZ, Soto R, Petersen C, Chiaro T, Gogokhia L, Bell R, Ajami NJ, Petrosino JF, Morrison L, Potts WK, Jensen PE, OConnell RM, Round JL (2015). MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection. Nat Commun, 6, 8642.
  13. Alexander M, Hu R, Runtsch MC, Kagele DA, Mosbruger TL, Tolmachova T, Seabra MC, Round JL, Ward DM, OConnell RM (2015). Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat Commun, 6, 7321.
  14. Kubinak JL, Petersen C, Stephens WZ, Soto R, Bake E, OConnell RM, Round JL (2015). MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health. Cell Host Microbe, 17(2), 153-63.
  15. Hu R, Kagele DA, Huffaker TB, Runtsch MC, Alexander M, Liu J, Bake E, Su W, Williams MA, Rao DS, Mller T, Garden GA, Round JL, OConnell RM (2014). miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation. Immunity, 41(4), 605-19.
  16. Lochhead RB, Ma Y, Zachary JF, Baltimore D, Zhao JL, Weis JH, OConnell RM, Weis JJ (2014). MicroRNA-146a provides feedback regulation of lyme arthritis but not carditis during infection with Borrelia burgdorferi. PLoS Pathog, 10(6), e1004212.
  17. Zhao JL, Ma C, OConnell RM, Mehta A, DiLoreto R, Heath JR, Baltimore D (2014). Conversion of danger signals into cytokine signals by hematopoietic stem and progenitor cells for regulation of stress-induced hematopoiesis. Cell Stem Cell, 14(4), 445-459.
  18. Hu R, Huffaker TB, Kagele DA, Runtsch MC, Bake E, Chaudhuri AA, Round JL, OConnell RM (2013). MicroRNA-155 confers encephalogenic potential to Th17 cells by promoting effector gene expression. J Immunol, 190(12), 5972-80.
  19. Zhao JL, Rao DS, OConnell RM, Garcia-Flores Y, Baltimore D (2013). MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice. eLife, 2, e00537.
  20. Hu R, Wallace J, Dahlem TJ, Grunwald DJ, OConnell RM (2013). Targeting human microRNA genes using engineered Tal-effector nucleases (TALENs). PLoS ONE, 8(5), e63074.
  21. Huffaker TB, Hu R, Runtsch MC, Bake E, Chen X, Zhao J, Round JL, Baltimore D, OConnell RM (2012). Epistasis between microRNAs 155 and 146a during T cell-mediated antitumor immunity. Cell Rep, 2(6), 1697-709.
  22. Chaudhuri AA, So AY, Mehta A, Minisandram A, Sinha N, Jonsson VD, Rao DS, OConnell RM, Baltimore D (2012). Oncomir miR-125b regulates hematopoiesis by targeting the gene Lin28A. Proc Natl Acad Sci U S A, 109(11), 4233-8.
  23. Zhao JL, Rao DS, Boldin MP, Taganov KD, OConnell RM, Baltimore D (2011). NF-kappaB dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies. Proc Natl Acad Sci U S A, 108(22), 9184-9.
  24. OConnell RM, Kahn D, Gibson WS, Round JL, Scholz RL, Chaudhuri AA, Kahn ME, Rao DS, Baltimore D (2010). MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity, 33(4), 607-19.
  25. OConnell RM, Chaudhuri AA, Rao DS, Gibson WS, Balazs AB, Baltimore D (2010). MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output. Proc Natl Acad Sci U S A, 107(32), 14235-40.
  26. Rao DS, OConnell RM, Chaudhuri AA, Garcia-Flores Y, Geiger TL, Baltimore D (2010). MicroRNA-34a perturbs B lymphocyte development by repressing the forkhead box transcription factor Foxp1. Immunity, 33(1), 48-59.
  27. OConnell RM, Rao DS, Chaudhuri AA, Baltimore D (2010). Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol, 10(2), 111-22.
  28. OConnell RM, Chaudhuri AA, Rao DS, Baltimore D (2009). Inositol phosphatase SHIP1 is a primary target of miR-155. Proc Natl Acad Sci U S A, 106(17), 7113-8.
  29. OConnell RM, Rao DS, Chaudhuri AA, Boldin MP, Taganov KD, Nicoll J, Paquette RL, Baltimore D (2008). Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J Exp Med, 205(3), 585-94.
  30. OConnell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D (2007). MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A, 104(5), 1604-9.
  31. Miller LS, OConnell RM, Gutierrez MA, Pietras EM, Shahangian A, Gross CE, Thirumala A, Cheung AL, Cheng G, Modlin RL (2006). MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureus. Immunity, 24(1), 79-91.
  32. OConnell RM, Vaidya SA, Perry AK, Saha SK, Dempsey PW, Cheng G (2005). Immune activation of type I IFNs by Listeria monocytogenes occurs independently of TLR4, TLR2, and receptor interacting protein 2 but involves TNFR-associated NF kappa B kinase-binding kinase 1. J Immunol, 174(3), 1602-7.
  33. Joseph SB, Bradley MN, Castrillo A, Bruhn KW, Mak PA, Pei L, Hogenesch J, Oconnell RM, Cheng G, Saez E, Miller JF, Tontonoz P (2004). LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell, 119(2), 299-309.
  34. OConnell RM, Saha SK, Vaidya SA, Bruhn KW, Miranda GA, Zarnegar B, Perry AK, Nguyen BO, Lane TF, Taniguchi T, Miller JF, Cheng G (2004). Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J Exp Med, 200(4), 437-45.
  35. Doyle SE, OConnell RM, Miranda GA, Vaidya SA, Chow EK, Liu PT, Suzuki S, Suzuki N, Modlin RL, Yeh WC, Lane TF, Cheng G (2004). Toll-like receptors induce a phagocytic gene program through p38. J Exp Med, 199(1), 81-90.
  36. Doyle SE, OConnell R, Vaidya SA, Chow EK, Yee K, Cheng G (2003). Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4. J Immunol, 170(7), 3565-71.
  37. Doyle S, Vaidya S, OConnell R, Dadgostar H, Dempsey P, Wu T, Rao G, Sun R, Haberland M, Modlin R, Cheng G (2002). IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity, 17(3), 251-63.

Review

  1. Wallace JA, OConnell RM (2017). MicroRNAs and acute myeloid leukemia: therapeutic implications and emerging concepts. [Review]. Blood, 130(11), 1290-1301.

Commentary

  1. Huffaker TB, OConnell RM (2015). miR-155-Socs1 as a Functional Axis: Satisfying the Burden of Proof. Immunity, 43(1)(Jul 21), 3-4.
  2. OConnell RM (2015). Endogenous miR-29a regulates HSC function in mammals. Blood, 125(14)(April 2), 2180-1.
  3. Hu R, OConnell RM (2012). MiR-23b is a safeguard against autoimmunity. Nat Med, 18(7)(Jul 6), 1009-10.

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