Ryan O'Connell

Ryan O'Connell, PhD

Languages spoken: English

Academic Information

Departments Primary - Pathology

Academic Office Information

ryan.oconnell@path.utah.edu

Lab

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

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

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

Selected Publications

Journal Article

  1. 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, OConnell RM, Vaeth M, Ussher J, Burgering BMT, Coffer PJ (2023). Pyruvate metabolism controls chromatin remodeling during CD4(+) T cell activation. Cell Rep, 42(6), 112583.
  2. Ren JG, Xing B, Lv K, OKeefe RA, Wu M, Wang R, Bauer KM, Ghazaryan A, Burslem GM, Zhang J, OConnell RM, Pillai V, Hexner EO, Philips MR, Tong W (2023). RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia. J Clin Invest, 133(12).
  3. Arnesen S, Polaski JT, Blanchard Z, Osborne KS, Welm AL, OConnell RM, Gertz J (2023). Estrogen receptor alpha mutations regulate gene expression and cell growth in breast cancer through microRNAs. NAR Cancer, 5(2), zcad027.
  4. Ghazaryan A, Wallace JA, Tang WW, Barba C, Lee SH, Bauer KM, Nelson MC, Kim CN, Stubben C, Voth WP, Rao DS, OConnell RM (2023). miRNA-1 promotes acute myeloid leukemia cell pathogenesis through metabolic regulation. Front Genet, 14, 1192799.
  5. Thompson JW, Hu R, Huffaker TB, Ramstead AG, Ekiz HA, Bauer KM, Tang WW, Ghazaryan A, Round JL, Fujinami RS, OConnell RM (2022). MicroRNA-155 Plays Selective Cell-Intrinsic Roles in Brain-Infiltrating Immune Cell Populations during Neuroinflammation. J Immunol, 210(7), 926-934.
  6. Barba C, Ekiz HA, Tang WW, Ghazaryan A, Hansen M, Lee SH, Voth WP, OConnell RM (2023). Interferon Gamma-Inducible NAMPT in Melanoma Cells Serves as a Mechanism of Resistance to Enhance Tumor Growth. Cancers (Basel), 15(5).
  7. Ramirez PW, Vollbrecht T, Acosta FM, Suarez M, Angerstein AO, Wallace J, O Connell RM, Guatelli J (2022). Nef enhances HIV-1 replication and infectivity independently of SERINC5 in CEM T cells. Virology, 578, 154-162.
  8. 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, OConnell RM (2022). CD11c+ myeloid cell exosomes reduce intestinal inflammation during colitis. JCI Insight, 7(19).
  9. Ferrara PJ, Yee EM, Petrocelli JJ, Fix DK, Hauser CT, de Hart NMMP, Mahmassani ZS, Reidy PT, OConnell RM, Drummond MJ (2022). Macrophage immunomodulation accelerates skeletal muscle functional recovery in aged mice following disuse atrophy. J Appl Physiol (1985), 133(4), 919-931.
  10. Bhatlekar S, Jacob S, Tugolukova E, Manne BK, Kosaka Y, Loher P, OConnell RM, Planelles V, Rondina MT, Rigoutsos I, Bray PF (2022). Interferon α-induced SAMHD1 regulates human cultured megakaryocyte apoptosis and proplatelet formation. Haematologica, 107(2), 558-561.
  11. Bhatlekar S, Jacob S, Manne BK, Guo L, Denorme F, Tugolukova EA, Cody MJ, Kosaka Y, Rigoutsos I, Campbell RA, Rowley JW, OConnell RM, Bray PF (2021). Megakaryocyte-specific knockout of the Mir-99b/let7e/125a cluster lowers platelet count without altering platelet function. Blood Cells Mol Dis, 92, 102624.
  12. Stephens WZ, Kubinak JL, Ghazaryan A, Bauer KM, Bell R, Buhrke K, Chiaro TR, Weis AM, Tang WW, Monts JK, Soto R, Ekiz HA, OConnell RM, Round JL (2020). Epithelial-myeloid exchange of MHC class II constrains immunity and microbiota composition. Cell Rep, 37(5), 109916.
  13. Fix DK, Ekiz HA, Petrocelli JJ, Mckenzie AM, Mahmassani ZS, OConnell RM, Drummond MJ (2021). Disrupted macrophage metabolic reprogramming in aged soleus muscle during early recovery following disuse atrophy. Aging Cell, 20(9), e13448.
  14. Ost KS, OMeara 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, OConnell RM, Cormack B, Ibrahim AS, Palm NW, Noble SM, Round JL (2021). Adaptive immunity induces mutualism between commensal eukaryotes. Nature, 596(7870), 114-118.
  15. Huffaker TB, Ekiz HA, Barba C, Lee SH, Runtsch MC, Nelson MC, Bauer KM, Tang WW, Mosbruger TL, Cox JE, Round JL, Voth WP, OConnell RM (2021). A Stat1 bound enhancer promotes Nampt expression and function within tumor associated macrophages. Nat Commun, 12(1), 2620.
  16. Dong J, Warner LM, Lin LL, Chen MC, OConnell RM, Lu LF (2019). miR-155 promotes T reg cell development by safeguarding medullary thymic epithelial cell maturation. J Exp Med, 218(2).
  17. Mangale V, Syage AR, Ekiz HA, Skinner DD, Cheng Y, Stone CL, Brown RM, OConnell RM, Green KN, Lane TE (2020). Microglia influence host defense, disease, and repair following murine coronavirus infection of the central nervous system. Glia, 68(11), 2345-2360.
  18. Bhatlekar S, Manne BK, Basak I, Edelstein LC, Tugolukova E, Stoller ML, Cody MJ, Morley SC, Nagalla S, Weyrich AS, Rowley JW, OConnell RM, Rondina MT, Campbell RA, Bray PF (2020). miR-125a-5p regulates megakaryocyte proplatelet formation via the actin-bundling protein L-plastin. Blood, 136(15), 1760-1772.
  19. Syage AR, Ekiz HA, Skinner DD, Stone C, OConnell RM, Lane TE (2020). Single-cell RNA sequencing reveals the diversity of the immunological landscape following CNS infection by a murine coronavirus. J Virol.
  20. Nelson MC, OConnell RM (2020). MicroRNAs: At the Interface of Metabolic Pathways and Inflammatory Responses by Macrophages. Front Immunol, 11, 1797.
  21. OConnell RM, Rao DS (2020). Microsized inflammaging protects stem cells. Blood, 135(25), 2204-2205.
  22. Niu F, Kazimierska M, Nolte IM, Terpstra MM, de Jong D, Koerts J, van der Sluis T, Rutgers B, OConnell RM, Kok K, van den Berg A, Dzikiewicz-Krawczyk A, Kluiver J (2020). The miR-26b-5p/KPNA2 Axis Is an Important Regulator of Burkitt Lymphoma Cell Growth. Cancers (Basel), 12(6).
  23. Ekiz HA, Conley CJ, Stephens WZ, OConnell RM (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.
  24. Ekiz HA, Ramstead AG, Lee SH, Nelson MC, Bauer KM, Wallace JA, Hu R, Round JL, Rutter J, Drummond MJ, Rao DS, OConnell RM (2020). T Cell-Expressed microRNA-155 Reduces Lifespan in a Mouse Model of Age-Related Chronic Inflammation. J Immunol, 204(8), 2064-2075.
  25. Snook JP, Soedel AJ, Ekiz HA, OConnell RM, Williams MA (2020). Inhibition of SHP-1 Expands the Repertoire of Antitumor T Cells Available to Respond to Immune Checkpoint Blockade. Cancer Immunol Res, 8(4), 506-517.
  26. Mahmassani ZS, Reidy PT, McKenzie AI, Petrocelli JJ, Matthews O, de Hart NM, Ferrara PJ, OConnell RM, Funai K, Drummond MJ (2020). Absence of MyD88 from Skeletal Muscle Protects Female Mice from Inactivity-Induced Adiposity and Insulin Resistance. Obesity (Silver Spring), 28(4), 772-782.
  27. Ramstead AG, Wallace JA, Lee SH, Bauer KM, Tang WW, Ekiz HA, Lane TE, Cluntun AA, Bettini ML, Round JL, Rutter J, OConnell RM (2018). Mitochondrial Pyruvate Carrier 1 Promotes Peripheral T Cell Homeostasis through Metabolic Regulation of Thymic Development. Cell Rep, 30(9), 2889-2899.e6.
  28. 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).
  29. 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.
  30. 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).
  31. 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.
  32. 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.
  33. 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.
  34. 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.
  35. 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.
  36. 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).
  37. 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.
  38. 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.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. 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.
  44. 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.
  45. 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.
  46. 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.
  47. 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.
  48. 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.
  49. 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.
  50. 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.
  51. 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.
  52. 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.
  53. 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.
  54. 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.
  55. 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.
  56. 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.
  57. 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.
  58. 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.
  59. 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.
  60. 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.
  61. 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.
  62. 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.
  63. 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.
  64. 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. Tang WW, Bauer KM, Barba C, Ekiz HA, OConnell RM (2022). miR-aculous new avenues for cancer immunotherapy. [Review]. Front Immunol, 13, 929677.
  2. Bauer KM, Round JL, OConnell RM (2021). No small matter: emerging roles for exosomal miRNAs in the immune system. [Review]. FEBS J, 289(14), 4021-4037.
  3. 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.

Other

  1. Hu R, OConnell RM (2012). MiR-23b is a safeguard against autoimmunity. Nat Med (18(7), pp. 1009-10). United States.

Patent

  1. O'Connell RM (2019). Treatment of autoimmune inflammation using miR-155.
  2. O'Connell RM (2019). Exosome delivery of microRNAs.
  3. O'Connell RM (2015). Regulation of Hematopoietic Stem Cell Functions Through Micrornas. U.S. Patent No. 9006195. Washington, D.C.:U.S. Patent and Trademark Office.
  4. Chaudhuri A, Yick-Lun So A, Baltimore D, O'Connell RM (2014). Regulation of Macrophage Activation Using MIR-125B. U.S. Patent No. 8685727. Washington, D.C.:U.S. Patent and Trademark Office.
  5. O'Connell RM (2009). Immunomodulating compounds and related compositions and methods.
  6. O'Connell RM (2008). miRNA inhibition for the treatment of inflammation and myeloproliferative disorders.