Our laboratory aims to investigate the roles of mobile genetic elements 61viral elements (EVEs), in diseases and host functions.In vivo experimentsMobile elementMobile elementIn vivo experimentsMouse geneticsDisease mechanismsPopulation geneticsPheWASCell experimentsMolecular biologyHi-CTransposoninsertionPhIP-seq(MEs), which include both transposable elements (TEs) and endogenous Endogenous bornavirus-like nucleoprotein elements (EBLNs) are EVEs closely related to Borna disease virus (BoDV). We previously found that mouse and human EBLNs are transcribed and processed into PIWI-interacting RNAs (piRNAs). With the known function of piRNAs to silence complementary RNA targets, we hypothesized that EBLN-derived piRNAs may silence BoDV mRNAs by RNA interference. Using genetically modified mice, we are testing if EBLN-derived piRNAs are involved in germline-encoded immune memory in mammals.Population geneticsMEs are a major source of genetic differences between people. We searched for endogenous human herpesvirus 6 (eHHV-6), an EVE found in about 1% of human genomes, in large biobanks and performed phenotype-wide association studies, or PheWAS, to determine which traits are associated with this EVE. We are also using cell lines derived from hundreds of different people to determine how different MEs and other genetic variants impact cellular responses to vari-ous perturbations, including chemical stimuli and virus infection.Molecular biologyMobilization of MEs introduces large-scale mutations, but we know only a few examples of how such mutations impact genome function. We are perform-ing chromatin conformation capture sequencing using iPS cells to find new examples of how TE insertions impact the conformation of surrounding DNA.eHHV-6 has been implicated in some diseases, but the evidence of causality remains inconclusive. Therefore, we aimed to establish a method to compre-hensively analyze anti-eHHV-6 antibodies. We employed phage immunopre-cipitation sequencing (PhIP-seq), which enables high-throughput antibody profiling by combining bacteriophage display with next-generation sequencing. We are currently screening human blood samples from patients to identify the viral epitopes associated with diseases.Figure: Schematic overview of our research activities. We use a combination of in vivo experiments, population genet-ics and molecular biology to uncover the mechanisms of how mobile genetic elements (MEs) are involved in diseases.Recent Major PublicationsSharif J, Koseki H, Parrish NF. Bridging multiple dimen-sions: roles of transposable elements in higher-order genome regulation. Curr Opin Genet Dev 80, 102035 (2023)Kojima S, Koyama S, Ka M, Saito Y, Parrish EH, Endo M, Takata S, Mizukoshi M, Hikino K, Takeda A, Gelinas AF, Heaton SM, Koide R, Kamada AJ, Noguchi M, Hamada M; Biobank Japan Project Consortium; Kamatani Y, Muraka-wa Y, Ishigaki K, Nakamura Y, Ito K, Terao C, Momozawa Y, Parrish NF. Mobile element variation contributes to population-specific genome diversification, gene regu-lation and disease risk. Nat Genet 55, 939-951 (2023)Parrish NF, Gaston DC. Metagenomics in infectious dis-ease diagnostics: Toward best-use practices to optimize actionable results. Transpl Infect Dis e13959 (2023)Invited presentationsParrish NF. “Mobile Genetic Elements in Health and Dis-ease” (Durham, USA) October 2023Kojima S. Parrish NF. “Mobile element variation drives population-specific genome diversification, gene regu-lation, and disease risk” Human Genetics Asia (Tokyo, Japan) October 2023Parrish NF. “Making Mobile Genetic Element Care Per-sonal” (Nashville, USA) July 2023Genome Immunobiology RIKEN Hakubi Research TeamTeam Leader: Nicholas Parrish
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