Ryan O'Connell

Ryan O'Connell, PhD

Languages spoken: English

Academic Information

Departments Primary - Pathology

Lab

I am currently a 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

Undergraduate California Lutheran University
 BS
Graduate Training University of the Pacific
 MS
Doctoral Training University of California, Los Angeles
 PhD
Postdoctoral Fellowship University of California at Los Angeles
 Postdoctoral Fellow
Postdoctoral Fellowship California Institute of Technology
 Postdoctoral Scholar

Selected Publications

Journal Article

  1. 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, O'Connell R (2017). miR-155 promotes FLT3-ITD-induced myeloproliferative disease through inhibition of the interferon response. Blood, 129(23), 3074-3086.
  2. O'Connell RM, Rao D (2020). Microsized inflammaging protects stem cells. Blood, 135(25), 2204-2205.
  3. Bhatlekar S, Manne BK, Basak I, Edelstein LC, Tugolukova E, Stoller ML, Cody MJ, Morley SC, Nagalla S, Weyrich AS, Rowley JW, O'Connell RM, Rondina MT, Campbell RA, Bray P (2020). miR-125a-5p regulates megakaryocyte proplatelet formation via the actin-bundling protein L-plastin. Blood, 136(15), 1760-1772.
  4. Joseph SB, Bradley MN, Castrillo A, Bruhn KW, Mak PA, Pei L, Hogenesch J, O'connell RM, Cheng G, Saez E, Miller JF, Tontonoz (2004). LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell, 119(2), 299-309.
  5. Mangale V, Syage AR, Ekiz HA, Skinner DD, Cheng Y, Stone CL, Brown RM, O'Connell RM, Green KN, Lane T (2020). Microglia influence host defense, disease, and repair following murine coronavirus infection of the central nervous system. Glia, 68(11), 2345-2360.
  6. 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 R (2017). Antitumor immunity is defective in T cell-specific microRNA-155-deficient mice and is rescued by immune checkpoint blockade. The Journal of biological chemistry, 292(45), 18530-18541.
  7. Doyle SE, O'Connell RM, Miranda GA, Vaidya SA, Chow EK, Liu PT, Suzuki S, Suzuki N, Modlin RL, Yeh WC, Lane TF, Cheng (2004). Toll-like receptors induce a phagocytic gene program through p38. The Journal of experimental medicine, 199(1), 81-90.
  8. O'Connell RM, Saha SK, Vaidya SA, Bruhn KW, Miranda GA, Zarnegar B, Perry AK, Nguyen BO, Lane TF, Taniguchi T, Miller JF, Cheng (2004). Type I interferon production enhances susceptibility to Listeria monocytogenes infection. The Journal of experimental medicine, 200(4), 437-45.
  9. O'Connell RM, Rao DS, Chaudhuri AA, Boldin MP, Taganov KD, Nicoll J, Paquette RL, Baltimore (2008). Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. The Journal of experimental medicine, 205(3), 585-94.
  10. Doyle SE, O'Connell R, Vaidya SA, Chow EK, Yee K, Cheng (2003). Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4. Journal of immunology (Baltimore, Md., 170(7), 3565-71.
  11. O'Connell RM, Vaidya SA, Perry AK, Saha SK, Dempsey PW, Cheng (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. Journal of immunology (Baltimore, Md., 174(3), 1602-7.
  12. Hu R, Huffaker TB, Kagele DA, Runtsch MC, Bake E, Chaudhuri AA, Round JL, O'Connell R (2013). MicroRNA-155 confers encephalogenic potential to Th17 cells by promoting effector gene expression. Journal of immunology (Baltimore, Md., 190(12), 5972-80.
  13. 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 R (2017). Rab27-Dependent Exosome Production Inhibits Chronic Inflammation and Enables Acute Responses to Inflammatory Stimuli. Journal of immunology (Baltimore, Md., 199(10), 3559-3570.
  14. Ekiz HA, Ramstead AG, Lee SH, Nelson MC, Bauer KM, Wallace JA, Hu R, Round JL, Rutter J, Drummond MJ, Rao DS, O'Connell R (2020). T Cell-Expressed microRNA-155 Reduces Lifespan in a Mouse Model of Age-Related Chronic Inflammation. Journal of immunology (Baltimore, Md., 204(8), 2064-2075.
  15. Syage AR, Ekiz HA, Skinner DD, Stone C, O'Connell RM, Lane T (2020). Single-cell RNA sequencing reveals the diversity of the immunological landscape following CNS infection by a murine coronavirus. Journal of virology,
  16. O'Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore (2007). MicroRNA-155 is induced during the macrophage inflammatory response. Proceedings of the National Academy of Sciences of the United States of America, 104(5), 1604-9.
  17. O'Connell RM, Chaudhuri AA, Rao DS, Baltimore (2009). Inositol phosphatase SHIP1 is a primary target of miR-155. Proceedings of the National Academy of Sciences of the United States of America, 106(17), 7113-8.
  18. O'Connell RM, Chaudhuri AA, Rao DS, Gibson WS, Balazs AB, Baltimore (2010). MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output. Proceedings of the National Academy of Sciences of the United States of America, 107(32), 14235-40.
  19. Zhao JL, Rao DS, Boldin MP, Taganov KD, O'Connell RM, Baltimore (2011). NF-kappaB dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies. Proceedings of the National Academy of Sciences of the United States of America, 108(22), 9184-9.
  20. Chaudhuri AA, So AY, Mehta A, Minisandram A, Sinha N, Jonsson VD, Rao DS, O'Connell RM, Baltimore (2012). Oncomir miR-125b regulates hematopoiesis by targeting the gene Lin28A. Proceedings of the National Academy of Sciences of the United States of America, 109(11), 4233-8.
  21. Petersen C, Bell R, Klag KA, Lee SH, Soto R, Ghazaryan A, Buhrke K, Ekiz HA, Ost KS, Boudina S, O'Connell RM, Cox JE, Villanueva CJ, Stephens WZ, Round J (2019). T cell-mediated regulation of the microbiota protects against obesity. Science (New York, N.Y.), 365(6451),
  22. Doyle S, Vaidya S, O'Connell R, Dadgostar H, Dempsey P, Wu T, Rao G, Sun R, Haberland M, Modlin R, Cheng (2002). IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity, 17(3), 251-63.
  23. Miller LS, O'Connell RM, Gutierrez MA, Pietras EM, Shahangian A, Gross CE, Thirumala A, Cheung AL, Cheng G, Modlin R (2006). MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureus. Immunity, 24(1), 79-91.
  24. Rao DS, O'Connell RM, Chaudhuri AA, Garcia-Flores Y, Geiger TL, Baltimore (2010). MicroRNA-34a perturbs B lymphocyte development by repressing the forkhead box transcription factor Foxp1. Immunity, 33(1), 48-59.
  25. O'Connell RM, Kahn D, Gibson WS, Round JL, Scholz RL, Chaudhuri AA, Kahn ME, Rao DS, Baltimore (2010). MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity, 33(4), 607-19.
  26. 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 R (2014). miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation. Immunity, 41(4), 605-19.
  27. Ekiz HA, Conley CJ, Stephens WZ, O'Connell R (2020). CIPR: a web-based R/shiny app and R package to annotate cell clusters in single cell RNA sequencing experiments. BMC bioinformatics, 21(1), 191.
  28. O'Connell RM, Rao DS, Chaudhuri AA, Baltimore (2010). Physiological and pathological roles for microRNAs in the immune system. Nature reviews. Immunology, 10(2), 111-22.
  29. Dickey LL, Worne CL, Glover JL, Lane TE, O'Connell R (2016). MicroRNA-155 enhances T cell trafficking and antiviral effector function in a model of coronavirus-induced neurologic disease. Journal of neuroinflammation, 13(1), 240.
  30. 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 R (2019). Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease. PLoS genetics, 15(2), e1007970.
  31. Lochhead RB, Ma Y, Zachary JF, Baltimore D, Zhao JL, Weis JH, O'Connell RM, Weis J (2014). MicroRNA-146a provides feedback regulation of lyme arthritis but not carditis during infection with Borrelia burgdorferi. PLoS pathogens, 10(6), e1004212.
  32. Mahmassani ZS, Reidy PT, McKenzie AI, Petrocelli JJ, Matthews O, de Hart NM, Ferrara PJ, O'Connell RM, Funai K, Drummond M (2020). Absence of MyD88 from Skeletal Muscle Protects Female Mice from Inactivity-Induced Adiposity and Insulin Resistance. Obesity (Silver Spring, Md.), 28(4), 772-782.
  33. Hu R, Wallace J, Dahlem TJ, Grunwald DJ, O'Connell R (2013). Targeting human microRNA genes using engineered Tal-effector nucleases (TALENs). PloS one, 8(5), e63074.
  34. Wallace J, Hu R, Mosbruger TL, Dahlem TJ, Stephens WZ, Rao DS, Round JL, O'Connell R (2016). Genome-Wide CRISPR-Cas9 Screen Identifies MicroRNAs That Regulate Myeloid Leukemia Cell Growth. PloS one, 11(4), e0153689.
  35. Kubinak JL, Petersen C, Stephens WZ, Soto R, Bake E, O'Connell RM, Round J (2015). MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health. Cell host & microbe, 17(2), 153-63.
  36. 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, O'Connell RM, Jacob V, Scherl E, Crawford C, Stephens WZ, Casjens SR, Longman RS, Round J (2019). Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis. Cell host & microbe, 25(2), 285-299.
  37. Zhao JL, Ma C, O'Connell RM, Mehta A, DiLoreto R, Heath JR, Baltimore (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.
  38. 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, O'Connell RM, Tebo AE, Round J (2017). A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice. Science translational medicine, 9(380),
  39. Alexander M, Hu R, Runtsch MC, Kagele DA, Mosbruger TL, Tolmachova T, Seabra MC, Round JL, Ward DM, O'Connell R (2015). Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nature communications, 6, 7321.
  40. 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 J (2015). MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection. Nature communications, 6, 8642.
  41. Niu F, Kazimierska M, Nolte IM, Terpstra MM, de Jong D, Koerts J, van der Sluis T, Rutgers B, O'Connell RM, Kok K, van den Berg A, Dzikiewicz-Krawczyk A, Kluiver (2020). The miR-26b-5p/KPNA2 Axis Is an Important Regulator of Burkitt Lymphoma Cell Growth. Cancers, 12(6),
  42. Nelson MC, O'Connell R (2020). MicroRNAs: At the Interface of Metabolic Pathways and Inflammatory Responses by Macrophages. Frontiers in immunology, 11, 1797.
  43. Huffaker TB, Hu R, Runtsch MC, Bake E, Chen X, Zhao J, Round JL, Baltimore D, O'Connell R (2012). Epistasis between microRNAs 155 and 146a during T cell-mediated antitumor immunity. Cell reports, 2(6), 1697-709.
  44. Ramstead AG, Wallace JA, Lee SH, Bauer KM, Tang WW, Ekiz HA, Lane TE, Cluntun AA, Bettini ML, Round JL, Rutter J, O'Connell R (2020). Mitochondrial Pyruvate Carrier 1 Promotes Peripheral T Cell Homeostasis through Metabolic Regulation of Thymic Development. Cell reports, 30(9), 2889-2899.e6.
  45. Zhao JL, Rao DS, O'Connell RM, Garcia-Flores Y, Baltimore (2013). MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice. eLife, 2, e00537.
  46. Brown DG, Soto R, Yandamuri S, Stone C, Dickey L, Gomes-Neto JC, Pastuzyn ED, Bell R, Petersen C, Buhrke K, Fujinami RS, O'Connell RM, Stephens WZ, Shepherd JD, Lane TE, Round J (2019). The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling. eLife, 8,
  47. Snook JP, Soedel AJ, Ekiz HA, O'Connell RM, Williams M (2020). Inhibition of SHP-1 Expands the Repertoire of Antitumor T Cells Available to Respond to Immune Checkpoint Blockade. Cancer immunology research, 8(4), 506-517.
  48. Ekiz HA, Huffaker TB, Grossmann AH, Stephens WZ, Williams MA, Round JL, O'Connell R (2019). MicroRNA-155 coordinates the immunological landscape within murine melanoma and correlates with immunity in human cancers. JCI insight, 4(6),
  49. Dong J, Warner LM, Lin LL, Chen MC, O'Connell RM, Lu L (2021). miR-155 promotes T reg cell development by safeguarding medullary thymic epithelial cell maturation. The Journal of experimental medicine, 218(2),
  50. 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 J (2021). Adaptive immunity induces mutualism between commensal eukaryotes. Nature, 596(7870), 114-118.
  51. 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 J (2021). Epithelial-myeloid exchange of MHC class II constrains immunity and microbiota composition. Cell reports, 37(5), 109916.
  52. Bhatlekar S, Jacob S, Manne BK, Guo L, Denorme F, Tugolukova EA, Cody MJ, Kosaka Y, Rigoutsos I, Campbell RA, Rowley JW, O'Connell RM, Bray P (2021). Megakaryocyte-specific knockout of the Mir-99b/let7e/125a cluster lowers platelet count without altering platelet function. Blood cells, molecules & diseases, 92, 102624.
  53. Bhatlekar S, Jacob S, Tugolukova E, Manne BK, Kosaka Y, Loher P, O'Connell RM, Planelles V, Rondina MT, Rigoutsos I, Bray P (2022). Interferon ¿-induced SAMHD1 regulates human cultured megakaryocyte apoptosis and proplatelet formation. Haematologica, 107(2), 558-561.
  54. Huffaker TB, Ekiz HA, Barba C, Lee SH, Runtsch MC, Nelson MC, Bauer KM, Tang WW, Mosbruger TL, Cox JE, Round JL, Voth WP, O'Connell R (2021). A Stat1 bound enhancer promotes Nampt expression and function within tumor associated macrophages. Nature communications, 12(1), 2620.
  55. Fix DK, Ekiz HA, Petrocelli JJ, Mckenzie AM, Mahmassani ZS, O'Connell RM, Drummond M (2021). Disrupted macrophage metabolic reprogramming in aged soleus muscle during early recovery following disuse atrophy. Aging cell, 20(9), e13448.
  56. Ferrara PJ, Yee EM, Petrocelli JJ, Fix DK, Hauser CT, de Hart NMMP, Mahmassani ZS, Reidy PT, O'Connell RM, Drummond M (2022). Macrophage immunomodulation accelerates skeletal muscle functional recovery in aged mice following disuse atrophy. Journal of applied physiology (Bethesda, Md., 133(4), 919-931.
  57. Ramirez PW, Vollbrecht T, Acosta FM, Suarez M, Angerstein AO, Wallace J, O' Connell RM, Guatelli (2023). Nef enhances HIV-1 replication and infectivity independently of SERINC5 in CEM T cells. Virology, 578, 154-162.
  58. Barba C, Ekiz HA, Tang WW, Ghazaryan A, Hansen M, Lee SH, Voth WP, O'Connell R (2023). Interferon Gamma-Inducible NAMPT in Melanoma Cells Serves as a Mechanism of Resistance to Enhance Tumor Growth. Cancers, 15(5),
  59. Bauer KM, Nelson MC, Tang WW, Chiaro TR, Brown DG, Ghazaryan A, Lee SH, Weis AM, Hill JH, Klag KA, Tran VB, Thompson JW, Ramstead AG, Monts JK, Marvin JE, Alexander M, Voth WP, Stephens WZ, Ward DM, Petrey AC, Round JL, O'Connell R (2022). CD11c+ myeloid cell exosomes reduce intestinal inflammation during colitis. JCI insight, 7(19),
  60. Thompson JW, Hu R, Huffaker TB, Ramstead AG, Ekiz HA, Bauer KM, Tang WW, Ghazaryan A, Round JL, Fujinami RS, O'Connell R (2023). MicroRNA-155 Plays Selective Cell-Intrinsic Roles in Brain-Infiltrating Immune Cell Populations during Neuroinflammation. Journal of immunology (Baltimore, Md., 210(7), 926-934.
  61. Ghazaryan A, Wallace JA, Tang WW, Barba C, Lee SH, Bauer KM, Nelson MC, Kim CN, Stubben C, Voth WP, Rao DS, O'Connell R (2023). miRNA-1 promotes acute myeloid leukemia cell pathogenesis through metabolic regulation. Frontiers in genetics, 14, 1192799.
  62. Arnesen S, Polaski JT, Blanchard Z, Osborne KS, Welm AL, O'Connell RM, Gertz (2023). Estrogen receptor alpha mutations regulate gene expression and cell growth in breast cancer through microRNAs. NAR cancer, 5(2), zcad027.
  63. Mocholi E, Russo L, Gopal K, Ramstead AG, Hochrein SM, Vos HR, Geeven G, Adegoke AO, Hoekstra A, van Es RM, Pittol JR, Vastert S, Rutter J, Radstake T, van Loosdregt J, Berkers C, Mokry M, Anderson CC, O'Connell RM, Vaeth M, Ussher J, Burgering BMT, Coffer P (2023). Pyruvate metabolism controls chromatin remodeling during CD4(+) T cell activation. Cell reports, 42(6), 112583.
  64. Ren JG, Xing B, Lv K, O'Keefe RA, Wu M, Wang R, Bauer KM, Ghazaryan A, Burslem GM, Zhang J, O'Connell RM, Pillai V, Hexner EO, Philips MR, Tong (2023). RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia. The Journal of clinical investigation, 133(12),

Review

  1. Wallace JA, O'Connell R (2017). MicroRNAs and acute myeloid leukemia: therapeutic implications and emerging concepts. Blood, 130(11), 1290-1301.
  2. Bauer KM, Round JL, O'Connell R (2022). No small matter: emerging roles for exosomal miRNAs in the immune system. The FEBS journal, 289(14), 4021-4037.
  3. Tang WW, Bauer KM, Barba C, Ekiz HA, O'Connell R (2022). miR-aculous new avenues for cancer immunotherapy. Frontiers in immunology, 13, 929677.

Commentary

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

Other

  1. Hu R, O'Connell R (2012). MiR-23b is a safeguard against autoimmunity. Nature medicine, 18(7), 1009-10.