June Round, PhD
- Microbial Pathogenesis
- Departments: Pathology - Associate Professor
- Divisions: Microbiology and Immunology
Academic Office Information
Emma Eccles Jones Medical Research Building
15 N Medical Dr E, Room: 4280A
Salt Lake City, UT
Research StatementThe mammalian immune system is charged with the task of recognizing microbial molecules and subsequently coordinating pathogen clearance. However, humans are host to a multitude of symbiotic microorganisms called the microbiota. This diverse consortium of bacteria take up residence on almost all environmentally exposed surfaces of the body, with the greatest diversity and number of organisms residing within the gastrointestinal (GI) tract. Since both pathogenic and commensal microorganisms share similar molecular patterns, it remains unclear how host immune responses toward symbiotic bacteria are prevented. Diseases such as inflammatory bowel disease, (IBD) result from a loss of host tolerance to commensal bacteria, thus understanding the mechanisms by which the host tolerates the microbiota and in turn how the microbiota influences the host immune system is paramount toward gaining a deeper understanding of mucosal biology and developing therapies for the treatment of intestinal disease.
Interests in the lab include 1) Understanding how T cell intrinsic Toll like receptor (TLRs) signaling governs T cell responses and how this impacts host tolerance toward the microbiota. 2) Identification and characterization of novel host genes within mucosal T cells regulated by the microbiota. 3) Understand how specific commensal organisms are able to regulate the host adaptive immune system and impact disease states.
In an effort to understand how commensal micro-organisms shape host immune responses we have focused our investigations on a prominent human commensal organism, Bacteriodes fragilis. We use animals raised in a completely sterile environment (called germ-free mice) as a model host organism. In this way we can associate the animals with a single species of bacteria and determine how these organisms are able to influence host immune system development. We have shown that animals colonized with B.fragilis are protected from inflammatory bowel disease. We have identified the molecule made by B.fragilis responsible for its protective activity and identified the host receptor that recognizes this molecule. Not only is this pathway important for host protection from disease but it is also plays a role in bacterial colonization. Thus we have uncovered a symbiotic communication circuit between host and bacteria that provides benefits to both members. Discovery of other pathways that exist between host and bacteria may lead to the discovery of bacterial products that could ultimately be used as therapies to treat human disease.
|Postdoctoral Fellowship||California Institute of Technology
Laboratory of Sarkis K. Mazmanian
|Doctoral Training||University of California at Los Angeles
Microbiology, Immunology and Molecular Genetics
|Graduate Training||University of the Pacific
|Undergraduate||California Lutheran University
Biology, (Cum Laude)
- Soto R, Petersen C, Novis CL, Kubinak JL, Bell R, Stephens WZ, Lane TE, Fujinami RS, Bosque A, OConnell RM, Round JL (2017 May 23). Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor. Proc Natl Acad Sci U S A, 114(21), 5497-5502.
- 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 Mar 8). A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice.LID - eaaf9044 [pii]LID - 10.1126/scitranslmed.aaf9044 [doi]. Sci Transl Med, 9(380).
- 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, OConnell RM (2015 Oct 6). MicroRNA-146a constrains multiple parameters of intestinal immunity and increases susceptibility to DSS colitis. Oncotarget, 6(30), 28556-72.
- Bennett MS, Round JL, Leung DT (2015 Oct). Innate-like lymphocytes in intestinal infections. Curr Opin Infect Dis, 28(5), 457-63.
- Kubinak JL, Petersen C, Stephens WZ, Soto R, Bake E, OConnell RM, Round JL (2015 Feb 11). MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health. Cell Host Microbe, 17(2), 153-63.
- 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.
- 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.
- Hu R, Kagele DA, Huffaker TB, Runtsch MC, Alexander M, Liu J, Bake E, Su W, Williams MA, Rao DS, Moller T, Garden GA, Round JL, OConnell RM (2014 Oct 16). miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation. Immunity, 41(4), 605-19.
- Stephens WZ, Round JL (2014 Sep 10). IgA targets the troublemakers. Cell Host Microbe, 16(3), 265-7.
- Novis CL, Archin NM, Buzon MJ, Verdin E, Round JL, Lichterfeld M, Margolis DM, Planelles V, Bosque A (2013). Reactivation of latent HIV-1 in central memory CD4(+) T cells through TLR-1/2 stimulation. Retrovirology, 10, 119.
- Huffaker TB, Hu R, Runtsch MC, Bake E, Chen X, Zhao J, Round JL, Baltimore D, OConnell RM (2012 Dec 27). Epistasis between microRNAs 155 and 146a during T cell-mediated antitumor immunity. Cell Rep, 2(6), 1697-709.
- Humphries LA, Shaffer MH, Sacirbegovic F, Tomassian T, McMahon KA, Humbert PO, Silva O, Round JL, Takamiya K, Huganir RL, Burkhardt JK, Russell SM, Miceli MC (2012). Characterization of in vivo Dlg1 deletion on T cell development and function. PLoS ONE, 7(9), e45276.
- Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, Mazmanian SK (2011 May 20). The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science, 332(6032), 974-7.
- OConnell RM, Kahn D, Gibson WS, Round JL, Scholz RL, Chaudhuri AA, Kahn ME, Rao DS, Baltimore D (2010 Oct 29). MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity, 33(4), 607-19.
- Round JL, Mazmanian SK (2010 Jul 6). Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A, 107(27), 12204-9.
- Mazmanian SK, Round JL, Kasper DL (2008 May 29). A microbial symbiosis factor prevents intestinal inflammatory disease. Nature, 453(7195), 620-5.
- Round JL, Humphries LA, Tomassian T, Mittelstadt P, Zhang M, Miceli MC (2007 Feb). Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors. Nat Immunol, 8(2), 154-61.
- Round JL, Tomassian T, Zhang M, Patel V, Schoenberger SP, Miceli MC (2005 Feb 7). Dlgh1 coordinates actin polymerization, synaptic T cell receptor and lipid raft aggregation, and effector function in T cells. J Exp Med, 201(3), 419-30.
- Zhang M, Moran M, Round J, Low TA, Patel VP, Tomassian T, Hernandez JD, Miceli MC (2005 Feb 1). CD45 signals outside of lipid rafts to promote ERK activation, synaptic raft clustering, and IL-2 production. J Immunol, 174(3), 1479-90.
- Song MJ, Hwang S, Wong W, Round J, Martinez-Guzman D, Turpaz Y, Liang J, Wong B, Johnson RC, Carey M, Sun R (2004 Dec). The DNA architectural protein HMGB1 facilitates RTA-mediated viral gene expression in gamma-2 herpesviruses. J Virol, 78(23), 12940-50.
- Nguyen L, Round J, OConnell R, Geurts P, Funes-Duran M, Wong J, Jongeward G, Vierra CA (2001 Nov 1). Isolation and characterization of the activated B-cell factor 1 homolog in Caenorhabditis elegans. Nucleic Acids Res, 29(21), 4423-32.
- Wong J, Funes-Duran M, Ahlberg J, Round J, OConnell R, Miller R, Chen E, Richmond PA, Vierra CA (2001 Aug). Characterization of a basic helix-loop-helix protein, ABF-1: nuclear localization, transcriptional properties, and interaction with Id-2. DNA Cell Biol, 20(8), 465-71.
- Petersen C, Round JL (2014 Jul). Defining dysbiosis and its influence on host immunity and disease. [Review]. Cell Microbiol, 16(7), 1024-33.
- Runtsch MC, Round JL, OConnell RM (2014). MicroRNAs and the regulation of intestinal homeostasis. [Review]. Front Genet, 5, 347.
- Kubinak JL, Round JL (2012). Toll-like receptors promote mutually beneficial commensal-host interactions. [Review]. PLoS Pathog, 8(7), e1002785.
- Round JL, OConnell RM, Mazmanian SK (2010 May). Coordination of tolerogenic immune responses by the commensal microbiota. [Review]. J Autoimmun, 34(3), J220-5.
- Round JL, Mazmanian SK (2009 May). The gut microbiota shapes intestinal immune responses during health and disease. [Review]. Nat Rev Immunol, 9(5), 313-23.
- Round JL (). From Fly to Man: Understanding how commensal micro-organisms influence host immunity and health. In David N. Fredricks (Ed.), The Human Microbiota: How Microbial Communities Affect Health and Disease. Wiley Blackwell.
- Round JL, Tomassian, T, Zhang, M, Patel, V, Schoenberger, SP and MC Miceli (). Dlgh1 coordinates actin polymerization, synaptic T cell receptor and lipid raft aggregation, and effector function in T cells. 2004 International Congress of Immunology/FOCIS, Clinical and Investigative Medicine, 27(4).
- Round JL (). Viruses storm the castle of IBD. Editor's choice. DOI: 10.1126/scitranslmed.aaa8320. Science Translational Medicine, 7:275EC35(Feb 2015).
- Round JL (). Quenching the fire fueling cancer in the gut. Editor's choice. DOI: 10.1126/scitranslmed.aaa3473. Science Translational Medicine, 7:269ec5(Jan 2015).
- Round JL (). Shaping up with gut microbia. Editor's choice. Science Translational Medicine, (Nov 2014).
- Round JL (). A case of mistaken identity: commensal bacteria direct the antibody response to HIV. Editor's Choice. DOI: 10.1126/scitranslamed.3010130. Science Translational Medicine, 6:251ec150(Aug 2014).
- Round JL (). An unexpected player in diabetes. Editor's choice. DOI: 10.1126/scitranslmed.3010130. Science Translational Medicine, 6:251ec150(Jul 2014).
- Round JL (). Genetic polymorphisms spill their guts. Editor's choice. DOI: 10.1126/scitranslmed.3009418. Science Translational Medicine, 6:239ec100(May 2014).
- Round JL (). Putting the brakes on inflammation: a novel therapy for sepsis. Editor's choice. Science Translational Medicine.
- Round JL (). A new innate cell on the block. Editor's Choice. DOI:10.1126/scitranslmed.3010423. Science Translational Medicine, 6(257ec174).
- Round JL, Tomassian T, Zhang M, Patel V, Schoenberger SP, Miceli MC (). Dlgh1 coordinates actin polymerization, synaptic T cell receptor and lipid raft aggregation, and effector function in T cells. Presented as a poster in 2004 International Congress of Immunology/FOCIS [Abstract]. Clinical and Invesigative Medicine, 27(4).
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