Ongoing and Current Projects
This page lists some of our ongoing research projects, along with representative publications for each. A full list of our publications can be found here.
1. Discovery of host factors that restrict replication of HIV-1 and other viruses
Yurkovetskiy L, Guney MH, Kim K, Goh SL, McCauley S, Dauphin A, Diehl WE, Luban J. Primate immunodeficiency virus proteins Vpx and Vpr counteract transcriptional repression of proviruses by the HUSH complex. Nat Microbiol. 2018 Dec;3(12):1354-1361.
Rosa A, Chande A, Ziglio S, De Sanctis V, Bertorelli R, Goh SL, McCauley SM, Nowosielska A, Antonarakis SE, Luban J, Santoni FA, Pizzato M. HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation. Nature. 2015 Oct 8;526(7572):212-7.
Neagu MR, Ziegler P, Pertel T, Strambio-De-Castillia C, Grütter C, Martinetti G, Mazzucchelli L, Grütter M, Manz MG, Luban J. Potent inhibition of HIV-1 by TRIM5-cyclophilin fusion proteins engineered from human components. J Clin Invest. 2009 Oct;119(10):3035-47.
2. Innate immune detection of HIV-1 and other retroviruses
Guney MH, Nagalekshmi K, McCauley SM, Carbone C, Aydemir O, Luban J.Weng Z, Theurkauf W. IFIH1 (MDA5) is required for type 1 interferon induction by intron-containing RNA expressed from the HIV-1 provirus. bioRxiv. 2023 Dec 12:2023.11.17.567619. doi: 10.1101/2023.11.17.567619. PMID: 38014177.
Yu T, Koppetsch BS, Pagliarani S, Johnston S, Silverstein NJ, Luban J, Chappell K, Weng Z, Theurkauf W. The piRNA response to retroviral invasion of the koala genome. Cell. 2019 Oct 17:179(3):632-643.e12.
McCauley SM, Kim K, Nowosielska A, Dauphin A, Yurkovetskiy L, Diehl WE, Luban J. Intron-containing RNA from the HIV-1 provirus activates type I interferon and inflammatory cytokines. Nat Commun. 2018 Dec 13;9(1):5305.
Lascano J, Uchil PD, Mothes W, Luban J. TRIM5 retroviral restriction activity correlates with the ability to induce innate immune signaling. J Virol. 2016 Jan 1;90(1):308-16.
Pertel T, Reinhard C, Luban J. Vpx rescues HIV-1 transduction of dendritic cells from the antiviral state established by type 1 interferon. Retrovirology. 2011 Jun 22;8:49.
Pertel T, Hausmann S, Morger D, Züger S, Guerra J, Lascano J, Reinhard C, Santoni FA, Uchil PD, Chatel L, Bisiaux A, Albert ML, Strambio-De-Castillia C, Mothes W, Pizzato M, Grütter MG, Luban J. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature. 2011 Apr 21;472(7343):361-5.
3. Host factors that promote HIV-1 replication.
Kim K, Dauphin A, Komurlu S, Yurkovetskiy L, Diehl WE, McCauley SM, Carbone C, Strambio-De-Castillia C, Campbell EM, Luban J. Cyclophilin A protects HIV-1 from restriction by human TRIM5alpha. Nature Microbiol, 2019 Dec;4(12):2044-2051. doi: 10.1038/s41564-019-0592-5. Epub 2019 Oct 21. PMID: 31636416.
De Iaco A, Santoni F, Vannier A, Guipponi M, Antonarakis S, Luban J. TNPO3 protects HIV-1 replication from CPSF6-mediated capsid stabilization in the host cell cytoplasm. Retrovirology. 2013 Feb 15;10:20.
Gurer C, Berthoux L, Luban J. Covalent modification of human immunodeficiency virus type 1 p6 by SUMO-1. J Virol. 2005 Jan;79(2):910-7.
Cimarelli A, Luban J. Translation elongation factor 1-alpha interacts specifically with the human immunodeficiency virus type 1 Gag polyprotein. J Virol. 1999 Jul;73(7):5388-401.
4. Viral pathogenesis, immunity, and characterization of immune cell types
Wang Y, Lifshitz L, Silverstein SJ, Mintzer E, Luk K, St Louis P, Brehm MA, Wolfe SA, Deeks SG, and Luban J. Transcriptional and chromatin profiling of human blood innate lymphoid cell subsets sheds light on HIV-1 pathogenesis. EMBO J. 2023 Aug 15;42(16):e114153. doi: 10.15252/embj.2023114153. Epub 2023 Jun 29. PMID: 37382276.
Silverstein NJ, Wang Y, Manickas-Hill Z, Carbone C, Dauphin A, Boribong BP, Loiselle M, Davis J, Leonard MM, Kuri-Cervantes L; MGH COVID-19 Collection & Processing Team, Meyer NJ, Betts MR, Li JZ, Walker BD, Yu XG, Yonker LM, Luban J. Comparative Analysis of Immune Cells Reveals a Conserved Regulatory Lexicon. Elife. 2022 Mar 11;11:e74681. doi: 10.7554/eLife.74681. Epub ahead of print. PMID:35275061.
Wang Y, Lifshitz L, Gellatly KJ, Vinton CL, Busman-Sahay K, McCauley SM, Vangala P, Kim K, Derr A, Smita J, Kucukural A, McDonel P, Hunt PW, Greenough T, Houghton JM, Samsouk M, Estes JD, Brenchley JM, Garber M, Deeks SG, Luban J. HIV-1-induced cytokines deplete homeostatic ILCs and expand TCF7-dependent memory NK cells. Nat. Immunol. 2020 Mar;21(3):274-286. doi: 10.1038/s41590-020-0593-9. Epub 2020 Feb 17. PMID: 32066947; PMCID: PMC7044076.
Gawron MA, Duval M, Carbone C, Jaiswal S, Wallace A, Martin JC 3rd, Dauphin A, Brehm MA, Greiner DL, Shultz LD, Luban J, Cavacini LA. Human Anti-HIV-1 gp120 Monoclonal Antibodies with Neutralizing Activity Cloned from Humanized Mice Infected with HIV-1. J Immunol. 2019 Feb 1;202(3):799-804.
Donnard E, Vangala P, Afik S, McCauley S, Nowosielska A, Kucukural A, Tabak B, Zhu X, Diehl W, McDonel P, Yosef N, Luban J, Garber M. Innate lymphoid cells and COVID-19 severity in SARS-CoV-2 infection. Cell Syst. 2018 Mar 28;6(3):381-394.e7.
Santoni FA, Guerra J, Luban J. HERV-H RNA is abundant in human embryonic stem cells and a precise marker for pluripotency. Retrovirology. 2012 Dec 20;9:111.
Colgan J, Asmal M, Neagu M, Yu B, Schneidkraut J, Lee Y, Sokolskaja E, Andreotti A, Luban J. Cyclophilin A regulates TCR signal strength in CD4+ T cells via a proline-directed conformational switch in Itk. Immunity. 2004 Aug;21(2):189-201.
Chang F, Re F, Sebastian S, Sazer S, Luban J. HIV-1 Vpr induces defects in mitosis, cytokinesis, nuclear structure, and centrosomes. Mol Biol Cell. 2004 Apr;15(4):1793-801
5. Virus evolution and disease outbreaks
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Yurkovetskiy L, Egri S, Kurhade C, Diaz-Salinas MA, Jaimes JA, Xie X, Nyalile T, Choudhary MC, Dauphin A, Li JZ, Munro JB, Shi P-Y, Shen K, and Luban J. S:D614G and S:H655Y are gateway mutations that act epistatically to promote SARS-CoV-2 variant fitness. bioRxiv. 2023 Apr 24:2023.03.30.535005. doi: 10.1101/2023.03.30.535005. Preprint. PMID: 37034621
Adams G, Moreno GK, Petros BA, Uddin R, Levine Z, Kotzen B, Messer K, Dobbins ST, DeRuff KC, Loreth C, Brock-Fisher T, Schaffner SF, Chaluvadi S, Kanjilal S, Luban J, Ozonoff A, Park D, Turbett S, Siddle KJ, MacInnis BL, Sabeti P, and Lemieux J. Viral lineages in the 2022 RSV surge in the United States. N Engl J Med. 2023 Feb 22. doi: 10.1056/NEJMc2216153. PMID: 36812457
Obermeyer F, Jankowiak M, Barkas N, Schaffner SF, Pyle JD, Yurkovetskiy L, Bosso M, Park DJ, Babadi M, MacInnis BL, Luban J, Sabeti PC, Lemieux JE. Analysis of 6.4 million SARS-CoV-2 genomes identifies mutations associated with fitness. Science. 2022 May 24:abm1208. Published online 2022 May 24. doi: 10.1126/science.abm1208. PMCID: PMC9161372. PMID: 35608456.
Yurkovetskiy L, Wang X, Pascal KE, Tomkins-Tinch C, Nyalile TP, Wang Y, Baum A, Diehl WE, Dauphin A, Carbone C, Veinotte K, Egri SB, Schaffner SF, Lemieux JE, Munro JB, Rafique A, Barve A, Sabeti PC, Kyratsous CA, Dudkina NV, Shen K, and Luban J. Structural and functional analysis of the D614G SARS-CoV-2 Spike protein variant. Cell 2020 Oct 29;183(3):739-751.e8. doi: 10.1016/j.cell.2020.09.032. Epub 2020 Sep 15. PMID: 32991842; PMCID: PMC7492024.
Diehl WE, Lin AE, Grubaugh ND, Carvalho LM, Kim K, Kyawe PP, McCauley SM, Donnard E, Kucukural A, McDonel P, Schaffner SF, Rambaut A, Garber M, Andersen, KG, Sabeti PC, and Jeremy Luban. Ebola virus glycoprotein with increased infectivity dominated the 2013-2016 epidemic. Cell. 2016 Nov 3;167(4):1088-1098.e6. doi: 10.1016/j.cell.2016.10.014. PMID: 27814506; PMCID: PMC5115602.