BukreyevLab_2020

The Bukreyev Lab

Our Lab focuses on investigation of the mechanisms of the high pathogenicity of viruses Ebola, Marburg and Lassa and development of vaccines and antibody treatments against these viruses. Our research includes the following specific topics:

  • Investigation of mechanisms of immunosuppression caused by these viruses.
  • Characterization of antibody responses to virus infections in humans.
  • Development of therapeutic human monoclonal antibody treatments.
  • Development of vaccines.
  • Comparative immunology of bats as a reservoir of emerging viral infections.
  • Experimental evolution of viruses in bats.

To get insight into these scientific topics, we are using molecular tools, including reverse genetics (i.e. development of genetically modified filoviruses from the DNA-copies of their genomes and use of mini-genomes), immunological tools such as multi-parameter flow cytometry, and human immune cells and animal models. Our research includes experiments in a BSL-2 labs and in BSL-4 labs of the Galveston National Laboratory. Our research is supported by grants from NIH and DoD.

Our collaborators include Dr. James Crowe, Jr. (Vanderbilt University), Dr. Erica Ollmann Saphire (La Jolla Institute for Immunology), Dr. Galit Alter (Ragon Institute), Dr. Thomas Geisbert (UTMB), Dr. Raul Andino (UCSF), Moderna, Inc. and other groups.

Lab Members

Dr. Alex Bukreyev alexander.bukreyev@utmb.edu
Dr. Kai Huang kahuang@utmb.edu
Dr. Philipp Ilinykhpailinyk@utmb.edu
Ms. Natalia Kuzminanakuzmin@utmb.edu
Ms. Nicole Lloyd nmlloyd@utmb.edu
Dr. Delphine Malherbedcmalher@utmb.edu
Dr. Michelle Meyermnmeyer@utmb.edu
Ms. Colette Peitzsch (Lab Manager) capietzs@utmb.edu
Dr. Palaniappan Ramanathanparamana@utmb.edu
Mr. Adam Ronk ajronk@utmb.edu
  
Administrative Assistant 
Ms. Dora Salinasdasalina@utmb.edu

Individuals interested in joining the lab as a Research Associate, a Postdoctoral Fellow or a Research Scientist should send a brief email and CV or resume directly to Dr. Bukreyev.


Selected publications from the lab

N. M. Lubaki, P. Ilinykh, C. Pietzsch, B. Tigabu, A. N. Freiberg, R. A. Koup, and A. Bukreyev (2013). The lack of maturation of Ebola virus-infected dendritic cells results from the cooperative effect of at least two viral domains. J. Virol. 87(13):7471-7485. The article was chosen for UTMB press release on 05/02/13.

P. A. Ilinykh, B. Tigabu, A. Ivanov, T. Ammosova,  Y. Obukhov, T. Garron, N. Kumari, D. Kovalskyy, M. O. Platonov, V. S. Naumchik,A. N. Freiberg, S. Nekhai, and A. Bukreyev (2014). Role of protein phosphatase 1 in dephosphorylation of Ebola virus VP30 and its targeting for the inhibition of viral transcription. J Biol. Chem. 289(33): 22723-38.

A. I. Flyak, P. A. Ilinykh, C. D. Murin, T. Garron, X. Shen, M. L. Fusco, T. Hashiguchi, Z. A. Bornholdt, J. C. Slaughter, G. Sapparapu, T. G. Ksiazek, A. B. Ward, E. O. Saphire, A. Bukreyev*, and J. E. Crowe, Jr.* (2015) Mechanism of human antibody-mediated neutralization of Marburg virus. Cell 160(5): 893-903. The article was chosen for UTMB and the Vanderbilt University press releases on 5/26/2015. *Co-senior authors.

P. Ilinykh, M. Lubaki, S. Widen, L. A. Renn, T. C. Theisen, N. R. Rabin, T. Wood, and A. Bukreyev (2015) Different temporal effects of Ebola virus VP35 and VP24 on global gene expression in human dendritic cells. J. Virol. 90(15):7567-83.

M. Meyer, T. Garron, N. M. Lubaki, C. E. Mire, K. A. Fenton, C. Klages, G. G. Olinger, T. W. Geisbert, P. L. Collins, and A. Bukreyev (2015) Aerosolized Ebola vaccine protects primates and elicits lung-resident T-cell responses. J. Clin. Invest. 125(8): 3241-55. The article was chosen for UTMB press release and NIH press release on 7/13/2015.

A. I. Flyak, X. Shen, C. D. Murin, H. L. Turner, M. L. Fusco, R. Lampley, N. Kose, P. A. Ilinykh, N. Kuzmina, A. Branchizio, H. King, L. Brown, C. Bryan, E. Davidson, B. J. Doranz, J. C. Slaughter, G. Sapparapu, C. Klages, T. G. Ksiazek, E. O. Saphire, A. B. Ward, A. Bukreyev,* and J. E. Crowe, Jr.* (2016) Cross-reactive and potent neutralizing antibody responses in human survivors of natural Ebolavirus infection. Cell 164(3): 392-405. The article was chosen for UTMB and the Vanderbilt University press releases on 1/21/2016, and was highlighted in Nature 529, 440. *Co-corresponding authors.

P. A. Ilinykh, X. Shen, A. I. Flyak, N. Kuzmina, T. G. Ksiazek, J. E. Crowe, Jr., and A. Bukreyev (2016) Chimeric filoviruses for identification and characterization of monoclonal antibodies. J. Virol. 90(8): 3890-901.

A. Rialdi, L. Campisi, N. Zhao, A. C. Lagda, C. Pietzsch, J. S. Ho, L. Martinez-Gil, R. Fenouil, X. Chen, M. Edwards, G. Metreveli, S. Jordan, Z. Peralta, C. Muniz-Fontela, N. Bouvier, M. Merad, J. Jin, M. Weirauch, S. Heinz, C. Benner, H. van Bakel, C. Basler, A. Garcia-Sastre, A. Bukreyev, and I. Marazzi. (2016) Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation. Science. 352 (6289): aad7993. The article was chosen for Icahn School of Medicine at Mount Sinai press releases on 4/28/2016.

N. M. Lubaki*, P. Younan*, R. I. Santos, M. Meyer, M. Iampietro, R. A. Koup, and A. Bukreyev. (2016). The Ebola interferon inhibiting domains attenuate and dysregulate cell-mediated immune responses. PLOS Pathogens 21(12):e1006031. The article was chosen for UTMB press releases on 12/01/2016. *Co-lead authors.

I. V. Kuzmin, T. M. Schwarz, P. A. Ilinykh, I. Jordan, T. G. Ksiazek, R. Sachidanandam, C. F. Basler, and A. Bukreyev (2017). Innate immune response of bat and human cells to filoviruses: commonalities and distinctions. J. Virol. 91(8):e02471-16.

P. Luthra, S. Aguirre, M. T. Sanchez, B. C. Yen, C. A. Pietzsch, B. Tigabu, L. Morlock, A. Garcia-Sastre, A. Sesma, N. Williams, A. Bukreyev, D. W. Leung, and C. Basler. (2017). Topoisomerase II inhibitors induce DNA Damage dependent interferon responses circumventing Ebola virus immune evasion. mBio. 8(2) e00368-17.

P. Younan, P. Ramanathan, J. Graber, F. Gusovsky, and A. Bukreyev. (2017). The TLR4 antagonist Eritoran protects mice from lethal filovirus challenge. mBio 8(2) e00226-17.

M. Iampietro*, P. Younan*, A. Nishida, M. Dutta, N. M. Lubaki, R. I. Santos, R. A. Koup, M. G. Katze, and A. Bukreyev. (2017). Ebola virus glycoprotein directly triggers T lymphocyte death despite of the lack of infection. PLOS Pathogens 13(5):e1006397. The article was chosen for UTMB press releases on 05/24/2017. *Co-lead authors.

P. Younan, M. Iampietro, A. Nishida, P. Ramanathan, R. I. Santos, M. Dutta, N. M. Lubaki, R. A. Koup, M. G. Katze, and A. Bukreyev. (2017). Ebola binding to Tim-1 on T-Lymphocytes induces a cytokine storm. mBio 8(5) e00845-17. The article was chosen for American Society of Microbiology and UTMB press releases on 09/26/2017.

L. B. King, M. L. Fusco, A. I. Flyak, P. A. Ilinykh, K. Huang, B. Gunn, R. N. Kirchdoerfer., K. M. Hastie, A. Sangha, J. Meiler, G. Alter, A. Bukreyev, J. E. Crowe, Jr., and E. Ollmann Saphire. (2018) Therapeutic human monoclonal antibody MR191against Marburg virus targets a conserved site to block receptor binding. Cell Host & Microbe 23(1):101-109.

M. Meyer, E. Huang, O. Yuzhakov, P. Ramanathan, G. Ciaramella, and A. Bukreyev. (2019) Modified mRNA-based vaccines elicit robust immune responses and protect guinea pigs from Ebola virus disease. J. Infect. Dis. 217(2):451-455.

M. Meyer, E. Huang, O. Yuzhakov, P. Ramanathan, G. Ciaramella, and A. Bukreyev (2018) Modified mRNA-based vaccines elicit robust immune responses and protect guinea pigs from Ebola virus disease. J. Infect. Dis. 217(2):451-455.

P. Younan, M. Iampietro and A. Bukreyev (2018). Disabling of lymphocyte immune response by Ebola Virus.PLOS Pathogens 14(4):e1006932.

E. O. Saphire, S. L. Schendel, M. L. Fusco, K. Gangavarapu, B. M. Gunn, A. Z. Wec, P. J. Halfmann, J. M. Brannan, A. S. Herbert, X. Qio et al. (2018). Systematic analysis of monoclonal antibodies against Ebola virus GP defines features that contribute to protection. Cell 174(4):938-952.

A. I. Flyak, N. Kuzmina, C. D. Murin, C. Bryan, E. Davidson, P. Gilchuk, C. P. Gulka, P. A. Ilinykh, X. Shen, P. Ramanathan, K. Huang, H. Turner, M. L. Fusco, R. Lampley, N. Kose, H. King, G. Sapparapu, B. J. Doranz, T. G. Ksiazek, D. W. Wright, E. Ollmann Saphire, A. B. Ward, A. Bukreyev*, and J. E. Crowe*, Jr. (2018). Neutralizing antibodies from human survivors target a conserved site in the ebolavirus glycoprotein HR2/MPER regions. *Co-corresponding author. Nature Microbiology 3(6):670-677.

P. Gilchuk, N. Kuzmina, P. A. Ilinykh, K. Huang, B. M. Gunn, A. Bryan, E. Davidson, B. J. Doranz, H. L. Turner, M. L. Fusco, M. S. Bramble, N. A. Hoff, E. Binshtein, N. Kose, A. I. Flyak,, R. Flinko, C. Orlandi, R. Carnahan, E. H. Parrish, A. M. Sevy, R. G. Bombardi, P. K. Singh, P. Mukadi, J. J. Muyembe-Tamfum, M. D. Ohi, E. Ollmann Saphire , G. K. Lewis, G. Alter, A. B. Ward, A. W. Rimoin, A. Bukreyev*, and J. E. Crowe, Jr*. (2018). Multifunctional pan-ebolavirus antibodies recognize a site of broad vulnerability on the ebolavirus glycoprotein. Immunity 49(2):363-374. *Co-corresponding author. The article was chosen for NIAID press releases on 07/17/2018.

M. Meyer, A. Yoshida, P. Ramanathan, E. Ollmann Saphire, P. Collins, J. E. Crowe Jr., S. Samal and A. Bukreyev (2018). Antibody repertoires to the same Ebola vaccine antigen are differentially affected by vaccine vectors. Cell Reports 24: 1816-1829.

N. A. Kuzmina, P. Younan, P. Gilchuk, R. I. Santos, A. I. Flyak, P. A. Ilinykh, K. Huang,   N. M. Lubaki, P. Ramanathan, J. E. Crowe, Jr.and A. Bukreyev (2018). Antibody-Dependent Enhancement of Ebola Virus Infection by Human Antibodies Isolated from Survivors. Cell Reports 24: 1802-1815.

M. Iampietro, R. I. Santos, N. M. Lubaki and A. Bukreyev (2018). Ebola Virus Shed GP Triggers Differentiation, Infection and Death of Monocytes Through TLR4 Activation. J. Infect. Dis. 218(Suppl. 5): S327-S334.

T. Ammosova, C. A. Pietzsch, Y. Saygideğer, A. Ilatovsky, X. Lin, A. Ivanov, N. Kumari, M. Jerebtsova, A. Kulkarni, M. Petukhov, A. Üren, A. Bukreyev* and Sergei Nekhai* (2018). Protein phosphatase-1-targeting small molecule C31 inhibits Ebola virus replication. J. Infect. Dis. 218 (Suppl. 5): S627-S635. *Co-corresponding author.

P. A. Ilinykh, J. Graber, N. A. Kuzmina, K. Huang, T. G. Ksiazek, J. E. Crowe, Jr. and A. Bukreyev (2018). Ebolavirus chimerization for the development of a mouse model for screening of Bundibugyo-specific antibodies. J. Infect. Dis. 218 (Suppl. 5): S418-S422.

P. A. Ilinykh, R. I. Santos, B. M. Gunn, N. A. Kuzmina, X. Shen, K. Huang, P. Gilchuk, A. I. Flyak, P. Younan, G. Alter, J. E. Crowe, Jr., and A. Bukreyev (2018). Assymetric antiviral effects of ebolavirus antibodies targeting glycoprotein stem and glycan cap. PLOS Pathogens 14(8):e1007204.

P. Younan, M. Iampietro, R. I. Santos, P. Ramanathan, V. L. Popov and A. Bukreyev (2018). Role of TMEM16F in the incorporation phosphatidylserine into budding ebolavirus virions. J. Infect. Dis. 218 (Suppl. 5): S335-S345.

P. Younan, M. Iampietro, R. I. Santos, P. Ramanathan, V. L. Popov and A. Bukreyev (2018). Disruption of phosphatidylserine synthesis or trafficking reduces infectivity of Ebola virus. J. Infect. Dis. 218 (Suppl. 5): S475-S485.

B. Tigabu, P. Ramanathan, A. Ivanov, X. Lin, P. A. Ilinykh, C. S. Parry, A. N. Freiberg, S. Nekhai and A. Bukreyev (2018). Phosphorylated VP30 of Marburg Virus is a Repressor of Transcription. J. Virol. 92(21):e00426-18.

M. Meyer, D. C. Malherbe and A. Bukreyev (2018). Can Ebola virus vaccines have universal correlates of protection? Trends in Microbiology 27(1):8-16.

J. Fang, C. Pietzsch, P. Ramanathan, R. I. Santos, P. A. Ilinykh, M. A. Garcia-Blanco, A. Bukreyev and S. S. Bradrick (2018). Staufen1 interacts with multiple components of the Ebola virus ribonucleoprotein and enhances viral RNA synthesis. mBio 9(5): e01771-18.

J. B. Kimble, D. C. Malherbe, M. Meyer, B. M. Gunn, M. M. Karim, P. A. Ilinykh, M. Iampietro, K. S. Mohamed, S. Negi, P. Gilchuk, K. Huang, Y I. Wolf, W. Braun, J. E. Crowe Jr., G. Alter and A. Bukreyev (2019). Antibody-mediated protective mechanisms induced by a trivalent parainfluenza-vectored ebolavirus vaccine. J. Virol. 93(4): e01845-18.

B. R. West, A. Z. Wec, C. L. Moyer, M. L. Fusco, P. A. Ilinykh, K. Huang, A. S. Wirchnianski, R. M. James, A. S. Herbert, S. Hui, E. Goodwin, K. A. Howell, S. Kailasan, M. J. Aman, L. M. Walker, J. M. Dye, A. Bukreyev, K. Chandran and E. Ollmann Saphire (2019). Structural Basis of Broad Ebolavirus Neutralization by a Human Survivor Antibody. Nature Structural & Molecular Biology 26(3):204-212.

L. B. King, B. R. West, C. L. Moyer, P. Gilchuk, A. Flyak, P. A. Ilinykh, R. Bombardi, S. Hui, K. Huang, A. Bukreyev, J. E. Crowe, Jr. and E. Ollmann Saphire (2019). Cross-reactive, neutralizing human survivor monoclonal antibody BDBV223 targets the ebolavirus stalk. Nature Communications 10 (1):1788.

P. Younan, R. I. Santos, P. Ramanathan, M. Iampietro, A. Nishida, M. Dutta, T. Ammosova, M. Meyer, M. G. Katze, V. L. Popov, S. Nekhai and A. Bukreyev (2019). Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection. PLOS Pathogens 15(10):e1008068. This article was chosen for UTMB Press Release on October 24, 2019.

A. Ivanov, P. Ramanathan, C. Parry, P. A. Ilinykh, X. Lin, Y. Obukhov, T. Ammosova, G. K Amarasinghe, A. Bukreyev* and S. Nekhai* (2019). Global phosphoproteomic analysis of Ebola virions reveals a novel role for VP35 phosphorylation-dependent regulation of genome transcription Cellular and Molecular Life Sciences *Co-corresponding author.

P. Gilchuk, D. Murin, J.C. Milligan, R.W. Cross, C.E. Mire, P.A. Ilinykh, K. Huang, N. Kuzmina, P.X. Altman, S. Hui, B.M. Gunn, A.L. Bryan, E. Davidson, B.J. Doranz, H.L. Turner, T. Alkutkar, R. Flinko, C. Orlandi, R. Carnahan, R. Nargi, R.G. Bombardi, M.E. Vodzak, S. Li, A. Okoli, M. Ibeawuchi, Ohiaeri, G.K. Lewis, G. Alter, A. Bukreyev, E. Ollmann Saphire, T.W. Geisbert, A.B. Ward and J.E. Crowe Jr. Structural and functional analysis of cooperativity in a potent human antibody cocktail against Ebola virus. ImmunityIn press.