{"id":56,"date":"2015-09-25T21:24:40","date_gmt":"2015-09-25T21:24:40","guid":{"rendered":"https:\/\/depts.washington.edu\/jaisril\/?page_id=56"},"modified":"2016-04-26T17:16:42","modified_gmt":"2016-04-26T17:16:42","slug":"overview","status":"publish","type":"page","link":"https:\/\/depts.washington.edu\/jaisril\/","title":{"rendered":"Overview"},"content":{"rendered":"<p>Jaisri Lingappa\u2019s lab studies how viruses hijack host proteins to promote assembly of human immunodeficiency virus type 1 (HIV-1) and other viruses, using biochemical and cell biological approaches.\u00a0 Our group has demonstrated that, in cells, the assembly of immature HIV-1 capsids occurs through a pathway of assembly intermediates, and is facilitated by the catalytic activity of the host enzymes ABCE1 and DDX6.\u00a0 To form assembly intermediates (also called \u201cassembly machines\u201d), HIV-1 co-opts sites of RNA metabolism called RNA granules.\u00a0 Our most recent studies suggest that:<\/p>\n<ul>\n<li>HIV-1 genomic RNA is largely sequestered within RNA granules in infected cells.<\/li>\n<li>The HIV-1 capsid protein Gag initiates genome packaging by entering RNA granules containing HIV-1 genomic RNA.<\/li>\n<li>A highly conserved viral-host interaction directs Gag to RNA granules containing HIV-1 genomic RNA.<\/li>\n<li>Mutations in Gag that arise <em>in vivo<\/em> alter the ability of Gag to enter RNA granules and progress through the assembly pathway, thereby altering the kinetics of virus production.<\/li>\n<\/ul>\n<p><a class=\"uw-btn btn-go btn-sm btn-gold\" href=\"\/jaisril\/research-background\/\">More Background on Our Research<\/a><br \/>\n<a class=\"uw-btn btn-go btn-sm btn-gold\" href=\"\/jaisril\/research-background\/current-research-questions\/\">About Our Current Research Questions<\/a><\/p>\n<h2>Recent Lingappa Lab Publications<\/h2>\n<p><!-- load from cache<br \/> --><\/p>\n<p><strong>Lingappa, AF, Akintunde, O, Samueli, E, Ewald, C, Michon, M, Ziari, N, Lu, M, Yu, SF, Froehlich, M, Le, PU, Fernandez, Y, Mallesh, S, Lin, J, Kitaygorodskyy, A, Solas, D, Reed, JC, Lingappa, JR, M\u00fcller-Schiffmann, A, Korth, C, Prasad, D, Nalca, A, Aston, E, Fabbri, B, Anand, SK, Campi, TW, Petrouski, E, Dey, D, Andrews, DW, Rubenstein, JL, Lingappa, VR<\/strong>. Small molecule protein assembly modulators with pan-cancer therapeutic efficacy. Open Biol. 2024;14 (12):240210. doi: <a href='http:\/\/dx.doi.org\/10.1098\/rsob.240210'>10.1098\/rsob.240210<\/a>. PubMed <a href='http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/39689856'>PMID:39689856<\/a> PubMed Central <a href='http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11651915'>PMC11651915<\/a>.<\/p>\n<p><strong>Michon, M, M\u00fcller-Schiffmann, A, Lingappa, AF, Yu, SF, Du, L, Deiter, F, Broce, S, Mallesh, S, Crabtree, J, Lingappa, UF, Macieik, A, M\u00fcller, L, Ostermann, PN, Andr\u00e9e, M, Adams, O, Schaal, H, Hogan, RJ, Tripp, RA, Appaiah, U, Anand, SK, Campi, TW, Ford, MJ, Reed, JC, Lin, J, Akintunde, O, Copeland, K, Nichols, C, Petrouski, E, Moreira, AR, Jiang, IT, DeYarman, N, Brown, I, Lau, S, Segal, I, Goldsmith, D, Hong, S, Asundi, V, Briggs, EM, Phyo, NS, Froehlich, M, Onisko, B, Matlack, K, Dey, D, Lingappa, JR, Prasad, DM, Kitaygorodskyy, A, Solas, D, Boushey, H, Greenland, J, Pillai, S, Lo, MK, Montgomery, JM, Spiropoulou, CF, Korth, C, Selvarajah, S, Paulvannan, K, Lingappa, VR<\/strong>. A pan-respiratory antiviral chemotype targeting a transient host multi-protein complex. Open Biol. 2024;14 (6):230363. doi: <a href='http:\/\/dx.doi.org\/10.1098\/rsob.230363'>10.1098\/rsob.230363<\/a>. PubMed <a href='http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/38889796'>PMID:38889796<\/a> PubMed Central <a href='http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11285769'>PMC11285769<\/a>.<\/p>\n<p><strong>Yu, SF, Paulvannan, K, Solas, D, Lingappa, AF, Moreira, AR, Sahu, S, Michon, M, Macieik, A, Goldsmith, D, DeYarman, N, Mallesh, S, Prasad, MD, Maios, C, Ruan, K, Tomassy, GS, Jensen, E, McGuirk, E, Bader, V, Mueller-Schiffmann, A, Reed, JC, Lingappa, JR, Asundi, V, Hong, S, Jacobsen, S, Brandon, N, Ostrow, L, Lloyd, T, Parker, JA, Staats, KA, Ichida, J, Dodge, JC, Dey, D, Korth, C, Selvarajah, S, Lingappa, VR, Rosenfeld, J<\/strong>. Protein Assembly Modulation: A New Approach to Amyotrophic Lateral Sclerosis (ALS) Therapeutics. J Exp Neurol. 2024;5 (4):210-230. doi: <a href='http:\/\/dx.doi.org\/10.33696\/Neurol.5.103'>10.33696\/Neurol.5.103<\/a>. PubMed <a href='http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/40977882'>PMID:40977882<\/a> PubMed Central <a href='http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC12445735'>PMC12445735<\/a>.<\/p>\n<p><strong>Michon, M, M\u00fcller-Schiffmann, A, Lingappa, AF, Yu, SF, Du, L, Deiter, F, Broce, S, Mallesh, S, Crabtree, J, Lingappa, UF, Macieik, A, M\u00fcller, L, Ostermann, PN, Andr\u00e9e, M, Adams, O, Schaal, H, Hogan, RJ, Tripp, RA, Appaiah, U, Anand, SK, Campi, TW, Ford, MJ, Reed, JC, Lin, J, Akintunde, O, Copeland, K, Nichols, C, Petrouski, E, Moreira, AR, Jiang, IT, DeYarman, N, Brown, I, Lau, S, Segal, I, Goldsmith, D, Hong, S, Asundi, V, Briggs, EM, Phyo, NS, Froehlich, M, Onisko, B, Matlack, K, Dey, D, Lingappa, JR, Prasad, MD, Kitaygorodskyy, A, Solas, D, Boushey, H, Greenland, J, Pillai, S, Lo, MK, Montgomery, JM, Spiropoulou, CF, Korth, C, Selvarajah, S, Paulvannan, K, Lingappa, VR<\/strong>. A Pan-Respiratory Antiviral Chemotype Targeting a Host Multi-Protein Complex. bioRxiv. 2023; :. doi: <a href='http:\/\/dx.doi.org\/10.1101\/2021.01.17.426875'>10.1101\/2021.01.17.426875<\/a>. PubMed <a href='http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/34931190'>PMID:34931190<\/a> PubMed Central <a href='http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8687465'>PMC8687465<\/a>.<\/p>\n<p><strong>Lingappa, JR, Lingappa, VR, Reed, JC<\/strong>. Addressing Antiretroviral Drug Resistance with Host-Targeting Drugs-First Steps towards Developing a Host-Targeting HIV-1 Assembly Inhibitor. Viruses. 2021;13 (3):. doi: <a href='http:\/\/dx.doi.org\/10.3390\/v13030451'>10.3390\/v13030451<\/a>. PubMed <a href='http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33802145'>PMID:33802145<\/a> PubMed Central <a href='http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8001593'>PMC8001593<\/a>.<\/p>\n<p><strong>Reed, JC, Solas, D, Kitaygorodskyy, A, Freeman, B, Ressler, DTB, Phuong, DJ, Swain, JV, Matlack, K, Hurt, CR, Lingappa, VR, Lingappa, JR<\/strong>. Identification of an Antiretroviral Small Molecule That Appears To Be a Host-Targeting Inhibitor of HIV-1 Assembly. J Virol. 2021;95 (3):. doi: <a href='http:\/\/dx.doi.org\/10.1128\/JVI.00883-20'>10.1128\/JVI.00883-20<\/a>. PubMed <a href='http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33148797'>PMID:33148797<\/a> PubMed Central <a href='http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7925099'>PMC7925099<\/a>.<\/p>\n<p><a class=\"uw-btn btn-go btn-sm btn-gold\" href=\"\/jaisril\/publications\/\">More\u00a0Publications<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Jaisri Lingappa\u2019s lab studies how viruses hijack host proteins to promote assembly of human immunodeficiency virus type 1 (HIV-1) and other viruses, using biochemical and cell biological approaches.\u00a0 Our group has demonstrated that, in cells, the assembly of immature HIV-1 capsids occurs through a pathway of assembly intermediates, and is facilitated by the catalytic activity&#8230;<\/p>\n<div><a class=\"more\" href=\"https:\/\/depts.washington.edu\/jaisril\/\">Read more<\/a><\/div>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-56","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/depts.washington.edu\/jaisril\/wp-json\/wp\/v2\/pages\/56","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/depts.washington.edu\/jaisril\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/depts.washington.edu\/jaisril\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/depts.washington.edu\/jaisril\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/depts.washington.edu\/jaisril\/wp-json\/wp\/v2\/comments?post=56"}],"version-history":[{"count":30,"href":"https:\/\/depts.washington.edu\/jaisril\/wp-json\/wp\/v2\/pages\/56\/revisions"}],"predecessor-version":[{"id":428,"href":"https:\/\/depts.washington.edu\/jaisril\/wp-json\/wp\/v2\/pages\/56\/revisions\/428"}],"wp:attachment":[{"href":"https:\/\/depts.washington.edu\/jaisril\/wp-json\/wp\/v2\/media?parent=56"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}