John Joseph Karijolich, Ph.D.

Associate Professor

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Faculty Appointments
Associate Professor of Pathology, Microbiology and Immunology Associate Professor of Biochemistry
Ph.D., University of Rochester, Rochester, New YorkB.A., Biology, Ripon College, Ripon, Wisconsin
Office Address
A4301 MCN
A4301 MCN
Nashville, TN 37232
Research Description
The association between infection with viruses and neoplasia is well established for a variety of cancers. In fact, approximately 12% of human cancers worldwide are caused by oncogenic viral infections, with more than 80% of cases occurring in the developing world. Despite their prevalence and public health importance, our understanding and ability to manage viral-induced cancers is still limited. This is in part due to the complexity of host-virus interactions leading to cellular transformation.

Research in our laboratory is focused on defining the host-virus interaction in the context of gammaherpesviral infection. ¿-herpesviruses, which include the human oncogenic viruses Kaposi Sarcoma-associated herpesvirus (KSHV) and Epstein Barr virus (EBV), are a family of large double-stranded DNA lymphotrophic viruses that are the causative agents of a variety of disorders, including lymphoproliferative diseases, lymphomas, as well as other nonlymphoid cancers in mammals. Studies of the host response to viral infection have historically focused on protein-coding genes, thus our understanding of how the non-protein-coding transcriptome, including both viral- and host-derived noncoding RNAs, impacts host-virus interactions is limited. Along this line, our primary research goals are directed towards understanding how noncoding RNAs and their RNA-binding proteins are integrated in to the regulation of gene expression and modulation of the host immune response during ¿-herpesviral infection. To accomplish this we undertake a multidisciplinary approach combining virology, immunology, RNA biochemistry, proteomics, and genomics/transcriptomics. Major thematic questions of the lab include:

1) What are the endogenous and exogenous noncoding RNA species that contribute to innate immune modulation and how are these functions mediated?

2) How does the cell intrinsic innate immune system shape the ¿-herpesviral lifecycle and what are the host and viral entities at play?

3) What is the contribution of endogenous retroviruses and transposons to the host-virus interaction?
Research Keywords
Host-pathogen interaction, noncoding RNA, innate immunity, endogenous retroviruses, retrotransposons, herpesviruses, gene expression, virology, cancer.
Ye X, Zhao Y, Karijolich J. The landscape of transcription initiation across latent and lytic KSHV genomes. PLoS Pathog. 2019 Jun; 15(6): e1007852. PMID: 31188901, PMCID: PMC6590836, PII: PPATHOGENS-D-19-00162, DOI: 10.1371/journal.ppat.1007852, ISSN: 1553-7374.

Heinrich MJ, Purcell CA, Pruijssers AJ, Zhao Y, Spurlock CF, Sriram S, Ogden KM, Dermody TS, Scholz MB, Crooke PS, Karijolich J, Aune TM. Endogenous double-stranded Alu RNA elements stimulate IFN-responses in relapsing remitting multiple sclerosis. J. Autoimmun [print-electronic]. 2019 Jun; 100: 40-51. PMID: 30826177, PMCID: PMC6513682, PII: S0896-8411(18)30699-1, DOI: 10.1016/j.jaut.2019.02.003, ISSN: 1095-9157.

Zhao Y, Ye X, Dunker W, Song Y, Karijolich J. RIG-I like receptor sensing of host RNAs facilitates the cell-intrinsic immune response to KSHV infection. Nat Commun. 2018 Nov 11/19/2018; 9(1): 4841. PMID: 30451863, PMCID: PMC6242832, PII: 10.1038/s41467-018-07314-7, DOI: 10.1038/s41467-018-07314-7, ISSN: 2041-1723.

Dunker W, Song Y, Zhao Y, Karijolich J. FUS Negatively Regulates Kaposi's Sarcoma-Associated Herpesvirus Gene Expression. Viruses. 2018 Jul 7/6/2018; 10(7): PMID: 29986386, PMCID: PMC6070805, PII: v10070359, DOI: 10.3390/v10070359, ISSN: 1999-4915.

Hesser CR, Karijolich J, Dominissini D, He C, Glaunsinger BA. N6-methyladenosine modification and the YTHDF2 reader protein play cell type specific roles in lytic viral gene expression during Kaposi's sarcoma-associated herpesvirus infection. PLoS Pathog. 2018 Apr; 14(4): e1006995. PMID: 29659627, PMCID: PMC5919695, PII: PPATHOGENS-D-17-02239, DOI: 10.1371/journal.ppat.1006995, ISSN: 1553-7374.

Zhao Y, Dunker W, Yu YT, Karijolich J. The Role of Noncoding RNA Pseudouridylation in Nuclear Gene Expression Events. Front Bioeng Biotechnol. 2018; 6: 8. PMID: 29473035, PMCID: PMC5809436, DOI: 10.3389/fbioe.2018.00008, ISSN: 2296-4185.

Dunker W, Zhao Y, Song Y, Karijolich J. Recognizing the SINEs of Infection: Regulation of Retrotransposon Expression and Modulation of Host Cell Processes. Viruses. 2017 Dec 12/18/2017; 9(12): PMID: 29258254, PMCID: PMC5744160, PII: v9120386, DOI: 10.3390/v9120386, ISSN: 1999-4915.

Ge J, Karijolich J, Zhai Y, Zheng J, Yu YT. 5-Fluorouracil Treatment Alters the Efficiency of Translational Recoding. Genes (Basel). 2017 Oct 10/31/2017; 8(11): PMID: 29088058, PMCID: PMC5704208, PII: genes8110295, DOI: 10.3390/genes8110295, ISSN: 2073-4425.

Karijolich J, Zhao Y, Alla R, Glaunsinger B. Genome-wide mapping of infection-induced SINE RNAs reveals a role in selective mRNA export. Nucleic Acids Res [print-electronic]. 2017 Mar 3/15/2017; PMID: 28334904, PII: 3071714, DOI: 10.1093/nar/gkx180, ISSN: 1362-4962.

Zhao Y, Karijolich J, Glaunsinger B, Zhou Q. Pseudouridylation of 7SK snRNA promotes 7SK snRNP formation to suppress HIV-1 transcription and escape from latency. EMBO Rep [print-electronic]. 2016 Aug 8/24/2016; PMID: 27558685, PII: embr.201642682, DOI: 10.15252/embr.201642682, ISSN: 1469-3178.

Huang C, Karijolich J, Yu YT. Detection and quantification of RNA 2'-O-methylation and pseudouridylation. Methods [print-electronic]. 2016 Jul 7/1/2016; 103: 68-76. PMID: 26853326, PMCID: PMC4921259, PII: S1046-2023(16)30021-4, DOI: 10.1016/j.ymeth.2016.02.003, ISSN: 1095-9130.

Karijolich J, Yi C, Yu YT. Transcriptome-wide dynamics of RNA pseudouridylation. Nat. Rev. Mol. Cell Biol [print-electronic]. 2015 Oct; 16(10): 581-5. PMID: 26285676, PII: nrm4040, DOI: 10.1038/nrm4040, ISSN: 1471-0080.

Karijolich J, Yu YT. The new era of RNA modification. RNA. 2015 Apr; 21(4): 659-60. PMID: 25780180, PMCID: PMC4371322, PII: 21/4/659, DOI: 10.1261/rna.049650.115, ISSN: 1469-9001.

Karijolich J, Abernathy E, Glaunsinger BA. Infection-Induced Retrotransposon-Derived Noncoding RNAs Enhance Herpesviral Gene Expression via the NF-¿B Pathway. PLoS Pathog. 2015; 11(11): e1005260. PMID: 26584434, PMCID: PMC4652899, PII: PPATHOGENS-D-15-02010, DOI: 10.1371/journal.ppat.1005260, ISSN: 1553-7374.

Karijolich J, Yu YT. Therapeutic suppression of premature termination codons: mechanisms and clinical considerations (review). Int. J. Mol. Med [print-electronic]. 2014 Aug; 34(2): 355-62. PMID: 24939317, PMCID: PMC4094583, DOI: 10.3892/ijmm.2014.1809, ISSN: 1791-244X.

Karijolich J, Zhao Y, Peterson B, Zhou Q, Glaunsinger B. Kaposi's sarcoma-associated herpesvirus ORF45 mediates transcriptional activation of the HIV-1 long terminal repeat via RSK2. J. Virol [print-electronic]. 2014 Jun; 88(12): 7024-35. PMID: 24719417, PMCID: PMC4054375, PII: JVI.00931-14, DOI: 10.1128/JVI.00931-14, ISSN: 1098-5514.

Lim SJ, Scott A, Xiong XP, Vahidpour S, Karijolich J, Guo D, Pei S, Yu YT, Zhou R, Li WX. Requirement for CRIF1 in RNA interference and Dicer-2 stability. RNA Biol. 2014; 11(9): 1171-9. PMID: 25483042, PMCID: PMC4615304, DOI: 10.4161/rna.34381, ISSN: 1555-8584.

Karijolich JJ, Hampsey M. The Mediator complex. Curr. Biol. 2012 Dec 12/18/2012; 22(24): R1030-1. PMID: 23257183, PII: S0960-9822(12)01320-6, DOI: 10.1016/j.cub.2012.11.011, ISSN: 1879-0445.

Karijolich J, Yu YT. Converting nonsense codons into sense codons by targeted pseudouridylation. Nature. 2011 Jun 6/16/2011; 474(7351): 395-8. PMID: 21677757, PMCID: PMC3381908, PII: nature10165, DOI: 10.1038/nature10165, ISSN: 1476-4687.

Huang C, Karijolich J, Yu YT. Post-transcriptional modification of RNAs by artificial Box H/ACA and Box C/D RNPs. Methods Mol. Biol. 2011; 718: 227-44. PMID: 21370052, PMCID: PMC4161979, DOI: 10.1007/978-1-61779-018-8_14, ISSN: 1940-6029.

Karijolich J, Yu YT. Spliceosomal snRNA modifications and their function. RNA Biol [print-electronic]. 2010 Mar; 7(2): 192-204. PMID: 20215871, PMCID: PMC4154345, PII: 11207, ISSN: 1555-8584.

Karijolich J, Kantartzis A, Yu YT. Quantitative analysis of RNA modifications. Methods Mol. Biol. 2010; 629: 21-32. PMID: 20387140, PMCID: PMC4154561, DOI: 10.1007/978-1-60761-657-3_2, ISSN: 1940-6029.

Karijolich J, Kantartzis A, Yu YT. RNA modifications: a mechanism that modulates gene expression. Methods Mol. Biol. 2010; 629: 1-19. PMID: 20387139, PMCID: PMC4154353, DOI: 10.1007/978-1-60761-657-3_1, ISSN: 1940-6029.

Karijolich J, Yu YT. Insight into the Protein Components of the Box H/ACA RNP. Curr Proteomics. 2008 Jul 7/1/2008; 5(2): 129-37. PMID: 19829749, PMCID: PMC2760984, DOI: 10.2174/157016408784911936, ISSN: 1570-1646.

Moelling C, Oberschlacke R, Ward P, Karijolich J, Borisova K, Bjelos N, Bergeron L. Metal-dependent repression of siderophore and biofilm formation in Actinomyces naeslundii. FEMS Microbiol. Lett [print-electronic]. 2007 Oct; 275(2): 214-20. PMID: 17825071, PII: FML888, DOI: 10.1111/j.1574-6968.2007.00888.x, ISSN: 0378-1097.

Karijolich J, Stephenson D, Yu YT. Biochemical purification of box H/ACA RNPs involved in pseudouridylation. Meth. Enzymol. 2007; 425: 241-62. PMID: 17673087, PII: S0076-6879(07)25011-6, DOI: 10.1016/S0076-6879(07)25011-6, ISSN: 0076-6879.