Micah Alan Luftig
Associate Professor of Molecular Genetics and Microbiology, with tenure
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.
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
- 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
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micah.luftig@duke.edu
(919) 668-3091
- Background
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Education, Training, & Certifications
- Ph.D., Harvard University 2003
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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
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In the News
- Expertise
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Subject Headings
- 3' Untranslated Regions
- Actin Cytoskeleton
- Adult
- Algorithms
- Animals
- Antibodies, Monoclonal
- Apoptosis
- Automation
- B-Lymphocytes
- Base Sequence
- Biological Markers
- Cell Adhesion Molecules
- Cell Cycle Proteins
- Cell Growth Processes
- Cell Line
- Cell Line, Transformed
- Cell Line, Tumor
- Cell Nucleus
- Cell Proliferation
- Cell Survival
- Cell Transformation, Neoplastic
- Cell Transformation, Viral
- Cells, Cultured
- Chromatin Immunoprecipitation
- Clone Cells
- Coculture Techniques
- Crystallography, X-Ray
- DNA Damage
- DNA Mutational Analysis
- DNA, Neoplasm
- DNA-Binding Proteins
- Epithelial Cells
- Epstein-Barr Virus Infections
- Epstein-Barr Virus Nuclear Antigens
- Epstein-barr Virus
- Exome
- Feeder Cells
- Gene Expression
- Gene Expression Profiling
- Gene Expression Regulation
- Gene Library
- Gene Order
- Genes, Reporter
- Genes, cdc
- Genetic Heterogeneity
- Genetic Variation
- Genetic Vectors
- HIV Envelope Protein gp41
- HIV-1
- Herpesvirus 1, Human
- Herpesvirus 4, Human
- High-Throughput Nucleotide Sequencing
- Host-Pathogen Interactions
- Humans
- Hydrophobic and Hydrophilic Interactions
- Interleukin-1 Receptor-Associated Kinases
- Leucine
- Leukemia, Lymphocytic, Chronic, B-Cell
- Luciferases
- Lymphocyte Activation
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Lymphoproliferative Disorders
- Macrophages
- Mass Spectrometry
- Mice
- MicroRNAs
- Microscopy, Electron
- Models, Biological
- Models, Molecular
- Molecular Sequence Data
- Molecular Targeted Therapy
- Molecular Weight
- Mutation
- NF-kappa B
- Neutralization Tests
- Oligonucleotide Array Sequence Analysis
- Oncogenes
- Oncogenic Viruses
- Peptide Fragments
- Phosphatidylinositol 3-Kinases
- Phosphorylation
- Piperazines
- Protein Binding
- Protein Conformation
- Protein Kinases
- Protein Structure, Quaternary
- Protein Structure, Secondary
- Protein Structure, Tertiary
- Protein Transport
- Protein-Serine-Threonine Kinases
- Proteins
- Proto-Oncogene Proteins c-kit
- RNA
- RNA, Messenger
- RNA, Viral
- Real-Time Polymerase Chain Reaction
- Receptor, Platelet-Derived Growth Factor alpha
- Receptors, Virus
- Recombinant Fusion Proteins
- Recombinant Proteins
- Retroviridae
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Analysis, RNA
- Sequence Homology, Nucleic Acid
- Signal Transduction
- Structure-Activity Relationship
- TNF Receptor-Associated Factor 6
- Transcription Factors
- Transduction, Genetic
- Transfection
- Tryptophan
- Tumor Cells, Cultured
- Tumor Suppressor Protein p53
- Tumor Suppressor Proteins
- Tumor Virus Infections
- Up-Regulation
- Vero Cells
- Viral Envelope Proteins
- Viral Matrix Proteins
- Viral Proteins
- Virus Internalization
- Virus Latency
- Virus Replication
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Global Scholarship
- Research
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Selected Grants
- Transplant Infectious Diseases Interdisciplinary Research Training Grant 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
- Targeting Apoptosis and Immune Control of Epstein-Barr Virus Infected Tonsillar B Cells awarded by National Institutes of Health 2016 - 2021
- Interdisciplinary Research Training Program in AIDS awarded by National Institutes of Health 2010 - 2020
- 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
- Novel Regulatory Controls of Hepatitis C Virus Envelopment and Secretion by the Viral NS4A Protein awarded by National Institutes of Health 2018 - 2020
- The role of EBNA3A in the survival of Epstein-Barr Virus-infected tonsillar B cells awarded by National Institutes of Health 2018 - 2020
- Viral Oncology Training Grant awarded by National Institutes of Health 1980 - 2019
- 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
- Publications & Artistic Works
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Selected Publications
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Academic Articles
- Stanland, LJ, and Luftig, MA. "Molecular features and translational outlook for Epstein–Barr virus-associated gastric cancer." Future Virology 13, no. 11 (November 2018): 803-818. Full Text
- Dai, J, and Luftig, MA. "Intracellular BH3 Profiling Reveals Shifts in Antiapoptotic Dependency in Human B Cell Maturation and Mitogen-Stimulated Proliferation." Journal of immunology (Baltimore, Md. : 1950) 200, no. 5 (March 2018): 1727-1736. Full Text
- Price, AM, Messinger, JE, and Luftig, MA. "c-Myc Represses Transcription of Epstein-Barr Virus Latent Membrane Protein 1 Early after Primary B Cell Infection." Journal of Virology 92, no. 2 (January 2, 2018). Full Text
- Hafez, AY, and Luftig, MA. "Characterization of the EBV-Induced Persistent DNA Damage Response." Viruses 9, no. 12 (December 2017). Full Text
- Poling, BC, Price, AM, Luftig, MA, and Cullen, BR. "The Epstein-Barr virus miR-BHRF1 microRNAs regulate viral gene expression in cis." Virology 512 (December 2017): 113-123. Full Text
- Grossman, L, Chang, C, Dai, J, Nikitin, PA, Jima, DD, Dave, SS, and Luftig, MA. "Epstein-Barr Virus Induces Adhesion Receptor CD226 (DNAM-1) Expression during Primary B-Cell Transformation into Lymphoblastoid Cell Lines." mSphere 2, no. 6 (November 29, 2017). Full Text
- Hafez, AY, Messinger, JE, McFadden, K, Fenyofalvi, G, Shepard, CN, Lenzi, GM, Kim, B, and Luftig, MA. "Limited nucleotide pools restrict Epstein-Barr virus-mediated B-cell immortalization." Oncogenesis 6, no. 6 (June 12, 2017): e349-. Full Text
- Price, AM, Dai, J, Bazot, Q, Patel, L, Nikitin, PA, Djavadian, R, Winter, PS, Salinas, CA, Barry, AP, Wood, KC, Johannsen, EC, Letai, A, Allday, MJ, and Luftig, MA. "Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection." Elife 6 (April 20, 2017). Full Text Open Access Copy
- Stanfield, BA, and Luftig, MA. "Recent advances in understanding Epstein-Barr virus." F1000Research 6 (January 2017): 386-. (Review) Full Text
- McFadden, K, Hafez, AY, Kishton, R, Messinger, JE, Nikitin, PA, Rathmell, JC, and Luftig, MA. "Metabolic stress is a barrier to Epstein-Barr virus-mediated B-cell immortalization." Proceedings of the National Academy of Sciences of the United States of America 113, no. 6 (February 2016): E782-E790. Full Text
- Price, AM, and Luftig, MA. "To be or not IIb: a multi-step process for Epstein-Barr virus latency establishment and consequences for B cell tumorigenesis." PLoS pathogens 11, no. 3 (March 19, 2015): e1004656-. (Review) Full Text
- Luftig, MA. "Viruses and the DNA Damage Response: Activation and Antagonism." Annual review of virology 1, no. 1 (November 2014): 605-625. Full Text
- Nikitin, PA, Price, AM, McFadden, K, Yan, CM, and Luftig, MA. "Mitogen-induced B-cell proliferation activates Chk2-dependent G1/S cell cycle arrest." Plos One 9, no. 1 (January 30, 2014): e87299-null. Full Text
- Price, AM, and Luftig, MA. "Dynamic Epstein-Barr virus gene expression on the path to B-cell transformation." Advances in Virus Research 88 (January 2014): 279-313. (Review) Full Text
- Luftig, M. "Heavy LIFting: tumor promotion and radioresistance in NPC." The Journal of Clinical Investigation 123, no. 12 (December 2013): 4999-5001. Full Text
- Homa, NJ, Salinas, R, Forte, E, Robinson, TJ, Garcia-Blanco, MA, and Luftig, MA. "Epstein-Barr virus induces global changes in cellular mRNA isoform usage that are important for the maintenance of latency." Journal of Virology 87, no. 22 (November 2013): 12291-12301. Full Text
- Olive, V, Sabio, E, Bennett, MJ, De Jong, CS, Biton, A, McGann, JC, Greaney, SK, Sodir, NM, Zhou, AY, Balakrishnan, A, Foth, M, Luftig, MA, Goga, A, Speed, TP, Xuan, Z, Evan, GI, Wan, Y, Minella, AC, and He, L. "A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis." Elife 2 (October 15, 2013): e00822-null. Full Text
- Zhang, J, Grubor, V, Love, CL, Banerjee, A, Richards, KL, Mieczkowski, PA, Dunphy, C, Choi, W, Au, WY, Srivastava, G, Lugar, PL, Rizzieri, DA, Lagoo, AS, Bernal-Mizrachi, L, Mann, KP, Flowers, C, Naresh, K, Evens, A, Gordon, LI, Czader, M, Gill, JI, Hsi, ED, Liu, Q, Fan, A, Walsh, K, Jima, D, Smith, LL, Johnson, AJ, Byrd, JC, Luftig, MA, Ni, T, Zhu, J, Chadburn, A, Levy, S, Dunson, D, and Dave, SS. "Genetic heterogeneity of diffuse large B-cell lymphoma." Proceedings of the National Academy of Sciences of the United States of America 110, no. 4 (January 4, 2013): 1398-1403. Full Text
- Forte, E, and Luftig, MA. "Use of viral systems to study miRNA-mediated regulation of gene expression in human cells." Methods Mol Biol 936 (2013): 143-156. Full Text Link to Item
- McFadden, K, and Luftig, MA. "Interplay between DNA tumor viruses and the host DNA damage response." Current Topics in Microbiology and Immunology 371 (January 2013): 229-257. (Review) Full Text
- McFadden, K, and Luftig, MA. "Interplay between DNA tumor viruses and the host DNA damage response." Current Topics in Microbiology and Immunology 371 (2013): 229-257. Full Text
- Price, AM, Tourigny, JP, Forte, E, Salinas, RE, Dave, SS, and Luftig, MA. "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." Journal of Virology 86, no. 20 (October 2012): 11096-11106. Full Text
- Robinson, TJ, Forte, E, Salinas, RE, Puri, S, Marengo, M, Garcia-Blanco, MA, and Luftig, MA. "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): 1435-1445. Full Text Link to Item
- Forte, E, Salinas, RE, Chang, C, Zhou, T, Linnstaedt, SD, Gottwein, E, Jacobs, C, Jima, D, Li, Q-J, Dave, SS, and Luftig, MA. "The Epstein-Barr virus (EBV)-induced tumor suppressor microRNA MiR-34a is growth promoting in EBV-infected B cells." Journal of Virology 86, no. 12 (June 2012): 6889-6898. Full Text
- Hwang, K-K, Chen, X, Kozink, DM, Gustilo, M, Marshall, DJ, Whitesides, JF, Liao, H-X, Catera, R, Chu, CC, Yan, X-J, Luftig, MA, Haynes, BF, and Chiorazzi, N. "Enhanced outgrowth of EBV-transformed chronic lymphocytic leukemia B cells mediated by coculture with macrophage feeder cells." Blood 119, no. 7 (February 2012): e35-e44. Full Text
- Skalsky, RL, Corcoran, DL, Gottwein, E, Frank, CL, Kang, D, Hafner, M, Nusbaum, JD, Feederle, R, Delecluse, H-J, Luftig, MA, Tuschl, T, Ohler, U, and Cullen, BR. "The viral and cellular microRNA targetome in lymphoblastoid cell lines." Plos Pathogens 8, no. 1 (January 26, 2012): e1002484-null. Full Text
- Nikitin, PA, and Luftig, MA. "The DNA damage response in viral-induced cellular transformation." British Journal of Cancer 106, no. 3 (January 12, 2012): 429-435. (Review) Full Text
- Forte, E, and Luftig, MA. "The role of microRNAs in Epstein-Barr virus latency and lytic reactivation." Microbes Infect 13, no. 14-15 (December 2011): 1156-1167. (Review) Full Text Link to Item
- Di Giovine, P, Settembre, EC, Bhargava, AK, Luftig, MA, Lou, H, Cohen, GH, Eisenberg, RJ, Krummenacher, C, and Carfi, A. "Structure of herpes simplex virus glycoprotein D bound to the human receptor nectin-1." PLoS Pathog 7, no. 9 (September 2011): e1002277-. Full Text Link to Item
- Nikitin, PA, and Luftig, MA. "At a crossroads: human DNA tumor viruses and the host DNA damage response." Future Virol 6, no. 7 (July 2011): 813-830. Full Text Link to Item
- Jima, DD, Zhang, J, Jacobs, C, Richards, KL, Dunphy, CH, Choi, WWL, Au, WY, Srivastava, G, Czader, MB, Rizzieri, DA, Lagoo, AS, Lugar, PL, Mann, KP, Flowers, CR, Bernal-Mizrachi, L, Naresh, KN, Evens, AM, Gordon, LI, Luftig, M, Friedman, DR, Weinberg, JB, Thompson, MA, Gill, JI, Liu, Q, How, T, Grubor, V, Gao, Y, Patel, A, Wu, H, Zhu, J, Blobe, GC, Lipsky, PE, Chadburn, A, Dave, SS, and Hematologic Malignancies Research Consortium, . "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-e127. Full Text Link to Item
- Nikitin, PA, Yan, CM, Forte, E, Bocedi, A, Tourigny, JP, White, RE, Allday, MJ, Patel, A, Dave, SS, Kim, W, Hu, K, Guo, J, Tainter, D, Rusyn, E, and Luftig, MA. "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 2010): 510-522. Full Text
- Linnstaedt, SD, Gottwein, E, Skalsky, RL, Luftig, MA, and Cullen, BR. "Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus." Journal of Virology 84, no. 22 (November 2010): 11670-11678. Full Text
- Bianchi, E, Joyce, J, Lloyd, C, Geleziunas, R, Bramhill, D, King, VM, Finnefrock, AC, Strohl, W, and An, Z. "Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41." Mabs 1, no. 5 (September 1, 2009): 458-469.
- Forte, E, and Luftig, MA. "MDM2-dependent inhibition of p53 is required for Epstein-Barr virus B-cell growth transformation and infected-cell survival." Journal of Virology 83, no. 6 (March 2009): 2491-2499. Full Text
- Montgomery, DL, Wang, Y-J, Hrin, R, Luftig, M, Su, B, Miller, MD, Wang, F, Haytko, P, Huang, L, Vitelli, S, Condra, J, Liu, X, Hampton, R, Carfi, A, Pessi, A, Bianchi, E, Joyce, J, Lloyd, C, Geleziunas, R, Bramhill, D, King, VM, Finnefrock, AC, Strohl, W, and An, Z. "Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41." mAbs 1, no. 5 (2009): 462-474.
- Luftig, MA, Mattu, M, Di Giovine, P, Geleziunas, R, Hrin, R, Barbato, G, Bianchi, E, Miller, MD, Pessi, A, and Carfí, A. "Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody." Nature Structural & Molecular Biology 13, no. 8 (August 2006): 740-747. Full Text
- Johannsen, E, Luftig, M, Chase, MR, Weicksel, S, Cahir-McFarland, E, Illanes, D, Sarracino, D, and Kieff, E. "Proteins of purified Epstein-Barr virus." Proceedings of the National Academy of Sciences of the United States of America 101, no. 46 (November 8, 2004): 16286-16291. Full Text
- Luftig, M, Yasui, T, Soni, V, Kang, M-S, Jacobson, N, Cahir-McFarland, E, Seed, B, and Kieff, E. "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): 141-146. Full Text Link to Item
- Yasui, T, Luftig, M, Soni, V, and Kieff, E. "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): 278-283. Full Text Link to Item
- Luftig, M, Prinarakis, E, Yasui, T, Tsichritzis, T, Cahir-McFarland, E, Inoue, J-I, Nakano, H, Mak, TW, Yeh, W-C, Li, X, Akira, S, Suzuki, N, Suzuki, S, Mosialos, G, and Kieff, E. "Epstein-Barr virus latent membrane protein 1 activation of NF-kappaB through IRAK1 and TRAF6." Proceedings of the National Academy of Sciences of the United States of America 100, no. 26 (December 12, 2003): 15595-15600. Full Text
- Luftig, MA, Cahir-McFarland, E, Mosialos, G, and Kieff, E. "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): 14602-14606. Full Text Link to Item
- Baghian, A, Luftig, M, Black, JB, Meng, YX, Pau, CP, Voss, T, Pellett, PE, and Kousoulas, KG. "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 2000): 18-25. Full Text
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- Teaching & Mentoring
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Recent Courses
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