Micah Alan Luftig | Scholars@Duke

Micah Alan Luftig
Associate Professor of Molecular Genetics and Microbiology

The laboratory focuses on the mechanisms by which Epstein-Barr virus activates and ultimately subverts the host oncogenic stress response to growth transform primary B lymphocytes into indefinitely proliferating lymphoblastoid cell lines (LCLs). EBV infection of B cells leads to a latent growth program where eight viral proteins and several non-coding RNAs are expressed. Among these gene products, latent membrane protein 1 (LMP1) and Epstein-Barr virus nuclear antigen (EBNA) 2 are the core transforming oncogenes. These proteins are capable of driving B cell proliferation and act to suppress the apoptotic response induced by aberrant S phase induction. The goals of the laboratory include: i) understanding the host pathways that respond to and suppress EBV-mediated growth transformation, ii) understanding the viral gene products important for activating the oncogenic stress response and ultimately overcoming this response, and iii) identifying and characterizing a cell population within the CD21-expressing primary B cell population that has an increased susceptibility to oncogenic stress.

The biochemical and genetic analyses of these pathways will provide valuable insight into our understanding of oncogenes and oncogenic viruses and the host cell response to such insults. Further, detailed understanding of the virus/host interaction may allow for the identification of specific pathways for therapeutic intervention in EBV-associated malignancies and possibly more broadly in malignancies which rely on similar pathways for their proliferation, survival, or self-renewal.

Current Appointments & Affiliations

Associate Professor of Molecular Genetics and Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2015
Vice-Chair in the Department of Molecular Genetics and Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2017
Associate Professor of Medicine, Medicine, Hematologic Malignancies and Cellular Therapy, Medicine 2017
Associate Professor of Immunology, Immunology, Basic Science Departments 2019
Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 2007

Contact Information

213 Research Dr, CARL 0036, Box 3054, Durham, NC 27710
Duke Box 3054, 424 CARL, Durham, NC 27710
micah.luftig@duke.edu (919) 668-3091

Background
Education, Training, & Certifications
- Ph.D., Harvard University 2003
Duke Appointment History
- Assistant Professor in Medicine, Medicine, Hematologic Malignancies and Cellular Therapy, Medicine 2012 - 2017
- Assistant Professor of Molecular Genetics and Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2008 - 2015
- Instructor, Temporary in the Department of Molecular Genetics and Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2007 - 2008
Recognition
In the News
- NOV 27, 2018
  
  Six From Duke Named Fellows of American Association for Advancement of Science
- JAN 19, 2016
  
  Disrupting Cell’s Supply Chain Freezes Cancer Virus
Expertise
Subject Headings
Global Scholarship
- Research
  - United Republic of Tanzania (Country)
Research
Selected Grants
- Interdisciplinary Research Training Program in AIDS awarded by National Institutes of Health 2010 - 2025
- Genetic and Genomics Training Grant awarded by National Institutes of Health 2020 - 2025
- Pharmacological Sciences Training Grant awarded by National Institutes of Health 2020 - 2025
- Dissecting the role of EBV and P. falciparum in endemic Burkitt lymphoma pathogenesis awarded by National Institutes of Health 2019 - 2024
- Viral Oncology Training Grant awarded by National Institutes of Health 1980 - 2024
- Transplant Infectious Diseases Interdisciplinary Research Training Grant (TIDIRTG) awarded by National Institutes of Health 2018 - 2023
- Host pathways regulating Epstein-Barr virus-mediated B cell growth transformation awarded by National Institutes of Health 2011 - 2021
- NIAID Virology Quality Assurance - Option 1 awarded by National Institutes of Health 2019 - 2021
- Targeting Apoptosis and Immune Control of Epstein-Barr Virus Infected Tonsillar B Cells awarded by National Institutes of Health 2016 - 2021
- Genetics Training Grant awarded by National Institutes of Health 1979 - 2020
- Organization and Function of Cellular Structure awarded by National Institutes of Health 1975 - 2020
- The role of EBNA3A in the survival of Epstein-Barr Virus-infected tonsillar B cells awarded by National Institutes of Health 2018 - 2019
- Novel regulatory controls of Hepatitis C Virus envelopment and secretion by the viral NS4A protein awarded by National Institutes of Health 2018
- Evaluation of the host immune response and viral molecular phenotype in lung transplant recipients with PTLD awarded by Mount Sinai School of Medicine 2017 - 2018
- Structural Studies of EBV Nuclear Proteins and Host Factors Important for Establishing Latency awarded by National Institutes of Health 2016 - 2018
- Temporal regulation of the essential Epstein-Barr virus oncoprotein LMP1 awarded by National Institutes of Health 2013 - 2016
External Relationships
- Evrys Bio
- Moderna Therapeutics, Inc.
Publications & Artistic Works
Selected Publications
- Academic Articles
  - Kaymaz, Yasin, Cliff I. Oduor, Ozkan Aydemir, Micah A. Luftig, Juliana A. Otieno, John Michael Ong’echa, Jeffrey A. Bailey, and Ann M. Moormann. “Epstein-Barr Virus Genomes Reveal Population Structure and Type 1 Association with Endemic Burkitt Lymphoma.” J Virol 94, no. 17 (August 17, 2020). https://doi.org/10.1128/JVI.02007-19.
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  - Purdy, John G., and Micah A. Luftig. “Reprogramming of cellular metabolic pathways by human oncogenic viruses.” Curr Opin Virol 39 (December 2019): 60–69. https://doi.org/10.1016/j.coviro.2019.11.002.
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  - Panea, Razvan I., Cassandra L. Love, Jennifer R. Shingleton, Anupama Reddy, Jeffrey A. Bailey, Ann M. Moormann, Juliana A. Otieno, et al. “The whole-genome landscape of Burkitt lymphoma subtypes.” Blood 134, no. 19 (November 7, 2019): 1598–1607. https://doi.org/10.1182/blood.2019001880.
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  - Messinger, Joshua E., Joanne Dai, Lyla J. Stanland, Alexander M. Price, and Micah A. Luftig. “Identification of Host Biomarkers of Epstein-Barr Virus Latency IIb and Latency III.” Mbio 10, no. 4 (July 2, 2019). https://doi.org/10.1128/mBio.01006-19.
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  - Stanland, L. J., and M. A. Luftig. “Molecular features and translational outlook for Epstein-Barr virus-associated gastric cancer.” Future Virology 13, no. 11 (November 1, 2018): 803–18. https://doi.org/10.2217/fvl-2018-0071.
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  - Dai, Joanne, and Micah A. Luftig. “Intracellular BH3 Profiling Reveals Shifts in Antiapoptotic Dependency in Human B Cell Maturation and Mitogen-Stimulated Proliferation.” J Immunol 200, no. 5 (March 1, 2018): 1727–36. https://doi.org/10.4049/jimmunol.1701473.
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  - Price, Alexander M., Joshua E. Messinger, and Micah A. Luftig. “c-Myc Represses Transcription of Epstein-Barr Virus Latent Membrane Protein 1 Early after Primary B Cell Infection.” J Virol 92, no. 2 (January 15, 2018). https://doi.org/10.1128/JVI.01178-17.
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  - Hafez, Amy Y., and Micah A. Luftig. “Characterization of the EBV-Induced Persistent DNA Damage Response.” Viruses 9, no. 12 (December 1, 2017). https://doi.org/10.3390/v9120366.
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  - Poling, Brigid Chiyoko, Alexander M. Price, Micah A. Luftig, and Bryan R. Cullen. “The Epstein-Barr virus miR-BHRF1 microRNAs regulate viral gene expression in cis.” Virology 512 (December 2017): 113–23. https://doi.org/10.1016/j.virol.2017.09.015.
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  - Grossman, Lisa, Chris Chang, Joanne Dai, Pavel A. Nikitin, Dereje D. Jima, Sandeep S. Dave, and Micah A. Luftig. “Epstein-Barr Virus Induces Adhesion Receptor CD226 (DNAM-1) Expression during Primary B-Cell Transformation into Lymphoblastoid Cell Lines.” Msphere 2, no. 6 (November 2017). https://doi.org/10.1128/mSphere.00305-17.
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  - Hafez, A. Y., J. E. Messinger, K. McFadden, G. Fenyofalvi, C. N. Shepard, G. M. Lenzi, B. Kim, and M. A. Luftig. “Limited nucleotide pools restrict Epstein-Barr virus-mediated B-cell immortalization.” Oncogenesis 6, no. 6 (June 12, 2017): e349. https://doi.org/10.1038/oncsis.2017.46.
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  - Price, Alexander M., Joanne Dai, Quentin Bazot, Luv Patel, Pavel A. Nikitin, Reza Djavadian, Peter S. Winter, et al. “Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection.” Elife 6 (April 20, 2017). https://doi.org/10.7554/eLife.22509.
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  - Stanfield, Brent A., and Micah A. Luftig. “Recent advances in understanding Epstein-Barr virus.” F1000res 6 (2017): 386. https://doi.org/10.12688/f1000research.10591.1.
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  - McFadden, Karyn, Amy Y. Hafez, Rigel Kishton, Joshua E. Messinger, Pavel A. Nikitin, Jeffrey C. Rathmell, and Micah A. Luftig. “Metabolic stress is a barrier to Epstein-Barr virus-mediated B-cell immortalization.” Proc Natl Acad Sci U S A 113, no. 6 (February 9, 2016): E782–90. https://doi.org/10.1073/pnas.1517141113.
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  - Price, Alexander M., and Micah A. Luftig. “To be or not IIb: a multi-step process for Epstein-Barr virus latency establishment and consequences for B cell tumorigenesis.” Plos Pathog 11, no. 3 (March 2015): e1004656. https://doi.org/10.1371/journal.ppat.1004656.
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  - Luftig, Micah A. “Viruses and the DNA Damage Response: Activation and Antagonism.” Annu Rev Virol 1, no. 1 (November 2014): 605–25. https://doi.org/10.1146/annurev-virology-031413-085548.
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  - Nikitin, Pavel A., Alexander M. Price, Karyn McFadden, Christopher M. Yan, and Micah A. Luftig. “Mitogen-induced B-cell proliferation activates Chk2-dependent G1/S cell cycle arrest.” Plos One 9, no. 1 (2014): e87299. https://doi.org/10.1371/journal.pone.0087299.
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  - Price, Alexander M., and Micah A. Luftig. “Dynamic Epstein-Barr virus gene expression on the path to B-cell transformation.” Adv Virus Res 88 (2014): 279–313. https://doi.org/10.1016/B978-0-12-800098-4.00006-4.
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  - Luftig, Micah. “Heavy LIFting: tumor promotion and radioresistance in NPC.” J Clin Invest 123, no. 12 (December 2013): 4999–5001. https://doi.org/10.1172/JCI73416.
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  - Homa, Nicholas J., Raul Salinas, Eleonora Forte, Timothy J. Robinson, Mariano A. Garcia-Blanco, and Micah A. Luftig. “Epstein-Barr virus induces global changes in cellular mRNA isoform usage that are important for the maintenance of latency.” J Virol 87, no. 22 (November 2013): 12291–301. https://doi.org/10.1128/JVI.02464-13.
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  - Olive, Virginie, Erich Sabio, Margaux J. Bennett, Caitlin S. De Jong, Anne Biton, James C. McGann, Samantha K. Greaney, et al. “A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis.” Elife 2 (October 15, 2013): e00822. https://doi.org/10.7554/eLife.00822.
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  - Zhang, Jenny, Vladimir Grubor, Cassandra L. Love, Anjishnu Banerjee, Kristy L. Richards, Piotr A. Mieczkowski, Cherie Dunphy, et al. “Genetic heterogeneity of diffuse large B-cell lymphoma.” Proc Natl Acad Sci U S A 110, no. 4 (January 22, 2013): 1398–1403. https://doi.org/10.1073/pnas.1205299110.
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  - Forte, Eleonora, and Micah A. Luftig. “Use of viral systems to study miRNA-mediated regulation of gene expression in human cells.” Methods Mol Biol 936 (2013): 143–56. https://doi.org/10.1007/978-1-62703-083-0_12.
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  - McFadden, Karyn, and Micah A. Luftig. “Interplay between DNA tumor viruses and the host DNA damage response.” Curr Top Microbiol Immunol 371 (2013): 229–57. https://doi.org/10.1007/978-3-642-37765-5_9.
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  - Price, Alexander M., Jason P. Tourigny, Eleonora Forte, Raul E. Salinas, Sandeep S. Dave, and Micah A. Luftig. “Analysis of Epstein-Barr virus-regulated host gene expression changes through primary B-cell outgrowth reveals delayed kinetics of latent membrane protein 1-mediated NF-κB activation.” J Virol 86, no. 20 (October 2012): 11096–106. https://doi.org/10.1128/JVI.01069-12.
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  - Robinson, Timothy J., Eleonora Forte, Raul E. Salinas, Shaan Puri, Matthew Marengo, Mariano A. Garcia-Blanco, and Micah A. Luftig. “SplicerEX: a tool for the automated detection and classification of mRNA changes from conventional and splice-sensitive microarray expression data.” Rna 18, no. 8 (August 2012): 1435–45. https://doi.org/10.1261/rna.033621.112.
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  - Forte, Eleonora, Raul E. Salinas, Christina Chang, Ting Zhou, Sarah D. Linnstaedt, Eva Gottwein, Cassandra Jacobs, et al. “The Epstein-Barr virus (EBV)-induced tumor suppressor microRNA MiR-34a is growth promoting in EBV-infected B cells.” J Virol 86, no. 12 (June 2012): 6889–98. https://doi.org/10.1128/JVI.07056-11.
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  - Hwang, Kwan-Ki, Xi Chen, Daniel M. Kozink, Marietta Gustilo, Dawn J. Marshall, John F. Whitesides, Hua-Xin Liao, et al. “Enhanced outgrowth of EBV-transformed chronic lymphocytic leukemia B cells mediated by coculture with macrophage feeder cells.” Blood 119, no. 7 (February 16, 2012): e35–44. https://doi.org/10.1182/blood-2011-08-371203.
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  - Nikitin, P. A., and M. A. Luftig. “The DNA damage response in viral-induced cellular transformation.” Br J Cancer 106, no. 3 (January 31, 2012): 429–35. https://doi.org/10.1038/bjc.2011.612.
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  - Skalsky, Rebecca L., David L. Corcoran, Eva Gottwein, Christopher L. Frank, Dong Kang, Markus Hafner, Jeffrey D. Nusbaum, et al. “The viral and cellular microRNA targetome in lymphoblastoid cell lines.” Plos Pathog 8, no. 1 (January 2012): e1002484. https://doi.org/10.1371/journal.ppat.1002484.
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  - Forte, Eleonora, and Micah A. Luftig. “The role of microRNAs in Epstein-Barr virus latency and lytic reactivation.” Microbes Infect 13, no. 14–15 (December 2011): 1156–67. https://doi.org/10.1016/j.micinf.2011.07.007.
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  - Di Giovine, Paolo, Ethan C. Settembre, Arjun K. Bhargava, Micah A. Luftig, Huan Lou, Gary H. Cohen, Roselyn J. Eisenberg, Claude Krummenacher, and Andrea Carfi. “Structure of herpes simplex virus glycoprotein D bound to the human receptor nectin-1.” Plos Pathog 7, no. 9 (September 2011): e1002277. https://doi.org/10.1371/journal.ppat.1002277.
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  - Nikitin, Pavel A., and Micah A. Luftig. “At a crossroads: human DNA tumor viruses and the host DNA damage response.” Future Virol 6, no. 7 (July 2011): 813–30. https://doi.org/10.2217/fvl.11.55.
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  - Nikitin, Pavel A., Christopher M. Yan, Eleonora Forte, Alessio Bocedi, Jason P. Tourigny, Robert E. White, Martin J. Allday, et al. “An ATM/Chk2-mediated DNA damage-responsive signaling pathway suppresses Epstein-Barr virus transformation of primary human B cells.” Cell Host Microbe 8, no. 6 (December 16, 2010): 510–22. https://doi.org/10.1016/j.chom.2010.11.004.
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  - Jima, Dereje D., Jenny Zhang, Cassandra Jacobs, Kristy L. Richards, Cherie H. Dunphy, William W. L. Choi, Wing Yan Au, et al. “Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs.” Blood 116, no. 23 (December 2, 2010): e118–27. https://doi.org/10.1182/blood-2010-05-285403.
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  - Linnstaedt, Sarah D., Eva Gottwein, Rebecca L. Skalsky, Micah A. Luftig, and Bryan R. Cullen. “Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus.” J Virol 84, no. 22 (November 2010): 11670–78. https://doi.org/10.1128/JVI.01248-10.
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  - Montgomery, D. L., Y. J. Wang, R. Hrin, M. Luftig, B. Su, M. D. Miller, F. Wang, et al. “Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41.” Mabs 1, no. 5 (September 1, 2009): 458–69.
  - Montgomery, Donna L., Ying-Jie Wang, Renee Hrin, Micah Luftig, Bin Su, Michael D. Miller, Fubao Wang, et al. “Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41.” Mabs 1, no. 5 (September 2009): 462–74. https://doi.org/10.4161/mabs.1.5.9214.
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  - Forte, Eleonora, and Micah A. Luftig. “MDM2-dependent inhibition of p53 is required for Epstein-Barr virus B-cell growth transformation and infected-cell survival.” J Virol 83, no. 6 (March 2009): 2491–99. https://doi.org/10.1128/JVI.01681-08.
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  - Luftig, Micah A., Marco Mattu, Paolo Di Giovine, Romas Geleziunas, Renee Hrin, Gaetano Barbato, Elisabetta Bianchi, Michael D. Miller, Antonello Pessi, and Andrea Carfí. “Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody.” Nat Struct Mol Biol 13, no. 8 (August 2006): 740–47. https://doi.org/10.1038/nsmb1127.
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  - Johannsen, Eric, Micah Luftig, Michael R. Chase, Steve Weicksel, Ellen Cahir-McFarland, Diego Illanes, David Sarracino, and Elliott Kieff. “Proteins of purified Epstein-Barr virus.” Proc Natl Acad Sci U S A 101, no. 46 (November 16, 2004): 16286–91. https://doi.org/10.1073/pnas.0407320101.
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  - Luftig, Micah, Teruhito Yasui, Vishal Soni, Myung-Soo Kang, Nils Jacobson, Ellen Cahir-McFarland, Brian Seed, and Elliott Kieff. “Epstein-Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK/IKK alpha-dependent noncanonical NF-kappaB activation.” Proc Natl Acad Sci U S A 101, no. 1 (January 6, 2004): 141–46. https://doi.org/10.1073/pnas.2237183100.
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  - Yasui, Teruhito, Micah Luftig, Vishal Soni, and Elliott Kieff. “Latent infection membrane protein transmembrane FWLY is critical for intermolecular interaction, raft localization, and signaling.” Proc Natl Acad Sci U S A 101, no. 1 (January 6, 2004): 278–83. https://doi.org/10.1073/pnas.2237224100.
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  - Luftig, Micah, Efthimios Prinarakis, Teruhito Yasui, Theodore Tsichritzis, Ellen Cahir-McFarland, Jun-Ichiro Inoue, Hiroyasu Nakano, et al. “Epstein-Barr virus latent membrane protein 1 activation of NF-kappaB through IRAK1 and TRAF6.” Proc Natl Acad Sci U S A 100, no. 26 (December 23, 2003): 15595–600. https://doi.org/10.1073/pnas.2136756100.
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  - Luftig, M. A., E. Cahir-McFarland, G. Mosialos, and E. Kieff. “Effects of the NIK aly mutation on NF-kappaB activation by the Epstein-Barr virus latent infection membrane protein, lymphotoxin beta receptor, and CD40.” J Biol Chem 276, no. 18 (May 4, 2001): 14602–6. https://doi.org/10.1074/jbc.C100103200.
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  - Baghian, A., M. Luftig, J. B. Black, Y. X. Meng, C. P. Pau, T. Voss, P. E. Pellett, and K. G. Kousoulas. “Glycoprotein B of human herpesvirus 8 is a component of the virion in a cleaved form composed of amino- and carboxyl-terminal fragments.” Virology 269, no. 1 (March 30, 2000): 18–25. https://doi.org/10.1006/viro.2000.0198.
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Teaching & Mentoring
Recent Courses
- MGM 293: Research Independent Study I 2020
- MGM 552: Virology 2020
- MGM 593: Research Independent Study 2020
- MGM 293: Research Independent Study I 2019
- MGM 552: Virology 2019
- MGM 593: Research Independent Study 2019
- MGM 293: Research Independent Study I 2018
- MGM 593: Research Independent Study 2018
- MGM 790S: Topics in Molecular Genetics and Microbiology 2018
- MGM 793: Research for Graduate Students 2018

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Education, Training, & Certifications

Duke Appointment History

In the News

Subject Headings

Global Scholarship

Research

Selected Grants

External Relationships

Selected Publications

Academic Articles

Recent Courses