Micah Luftig

Overview:

The Luftig laboratory studies viruses that cause cancer with an overarching goal of defining the basic molecular mechanisms underlying pathogenesis and leveraging these findings for diagnostic value and therapeutic intervention. Our work primarily focuses on the common herpesvirus, Epstein-Barr virus (EBV). This virus latently infects virtually all adults worldwide being acquired early in life. In the immune suppressed, EBV promotes lymphomas in the B cells that it naturally infects. However, EBV can also infect epithelial cells and other lymphocytes contributing to human cancers as wide-ranging as nasopharyngeal and gastric carcinoma to aggressive NK/T-cell, Burkitt, and Hodgkin lymphomas. Overall, EBV contributes to approximately 2% of all human cancers worldwide leading to nearly 200,000 deaths annually.

We use cutting-edge, cross-disciplinary and highly collaborative approaches to characterize the temporal dynamics and single cell heterogeneity of EBV infection. With these strategies, we aim to discover fundamental molecular circuits underlying transcriptional control, viral manipulation of host signaling pathways, and metabolic regulation that collectively influence infected cell fate decisions. By understanding the nature of viral control of infected host cells, we are also well positioned to discover vulnerabilities in EBV-associated diseases and characterize new therapeutic interventions in cell-based and pre-clinical animal models.

Positions:

Associate Professor of Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Vice-Chair in the Department of Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Associate Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Associate Professor of Immunology

Immunology
School of Medicine

Associate Professor of Cell Biology

Cell Biology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2003

Harvard University

Grants:

NIAID Virology Quality Assurance - Base to Opt 6

Administered By
Duke Human Vaccine Institute
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Novel regulatory controls of Hepatitis C Virus envelopment and secretion by the viral NS4A protein

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Co-Sponsor
Start Date
End Date

Host pathways regulating Epstein-Barr virus-mediated B cell growth transformation

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Targeting Apoptosis and Immune Control of Epstein-Barr Virus Infected Tonsillar B Cells

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

The role of EBNA3A in the survival of Epstein-Barr Virus-infected tonsillar B cells

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Epstein-Barr virus perpetuates B cell germinal center dynamics and generation of autoimmune-associated phenotypes in vitro.

Human B cells encompass functionally diverse lineages and phenotypic states that contribute to protective as well as pathogenic responses. Epstein-Barr virus (EBV) provides a unique lens for studying heterogeneous B cell responses, given its adaptation to manipulate intrinsic cell programming. EBV promotes the activation, proliferation, and eventual outgrowth of host B cells as immortalized lymphoblastoid cell lines (LCLs) in vitro, which provide a foundational model of viral latency and lymphomagenesis. Although cellular responses and outcomes of infection can vary significantly within populations, investigations that capture genome-wide perspectives of this variation at single-cell resolution are in nascent stages. We have recently used single-cell approaches to identify EBV-mediated B cell heterogeneity in de novo infection and within LCLs, underscoring the dynamic and complex qualities of latent infection rather than a singular, static infection state. Here, we expand upon these findings with functional characterizations of EBV-induced dynamic phenotypes that mimic B cell immune responses. We found that distinct subpopulations isolated from LCLs could completely reconstitute the full phenotypic spectrum of their parental lines. In conjunction with conserved patterns of cell state diversity identified within scRNA-seq data, these data support a model in which EBV continuously drives recurrent B cell entry, progression through, and egress from the Germinal Center (GC) reaction. This "perpetual GC" also generates tangent cell fate trajectories including terminal plasmablast differentiation, which constitutes a replicative cul-de-sac for EBV from which lytic reactivation provides escape. Furthermore, we found that both established EBV latency and de novo infection support the development of cells with features of atypical memory B cells, which have been broadly associated with autoimmune disorders. Treatment of LCLs with TLR7 agonist or IL-21 was sufficient to generate an increased frequency of IgD-/CD27-/CD23-/CD38+/CD138+ plasmablasts. Separately, de novo EBV infection led to the development of CXCR3+/CD11c+/FCRL4+ B cells within days, providing evidence for possible T cell-independent origins of a recently described EBV-associated neuroinvasive CXCR3+ B cell subset in patients with multiple sclerosis. Collectively, this work reveals unexpected virus-driven complexity across infected cell populations and highlights potential roles of EBV in mediating or priming foundational aspects of virus-associated immune cell dysfunction in disease.
Authors
SoRelle, ED; Reinoso-Vizcaino, NM; Horn, GQ; Luftig, MA
MLA Citation
SoRelle, Elliott D., et al. “Epstein-Barr virus perpetuates B cell germinal center dynamics and generation of autoimmune-associated phenotypes in vitro.Front Immunol, vol. 13, 2022, p. 1001145. Pubmed, doi:10.3389/fimmu.2022.1001145.
URI
https://scholars.duke.edu/individual/pub1553129
PMID
36248899
Source
pubmed
Published In
Frontiers in Immunology
Volume
13
Published Date
Start Page
1001145
DOI
10.3389/fimmu.2022.1001145

Studies at the oncogenic virus/host interface: Dynamic regulation of Epstein-Barr virus-mediated B cell immortalization

Authors
Luftig, M; Nikitin, P; Yan, C; Forte, E; Tourigny, J; Price, A; Dave, S
MLA Citation
Luftig, Micah, et al. “Studies at the oncogenic virus/host interface: Dynamic regulation of Epstein-Barr virus-mediated B cell immortalization.” Jaids Journal of Acquired Immune Deficiency Syndromes, vol. 62, 2013, pp. 58–58.
URI
https://scholars.duke.edu/individual/pub1532533
Source
wos-lite
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
62
Published Date
Start Page
58
End Page
58

Interplay Between DNA Tumor Viruses and the Host DNA Damage Response

Authors
McFadden, K; Luftig, MA
MLA Citation
McFadden, Karyn, and Micah A. Luftig. “Interplay Between DNA Tumor Viruses and the Host DNA Damage Response.” Current Topics in Microbiology and Immunology, Springer Berlin Heidelberg, 2013, pp. 229–57. Crossref, doi:10.1007/978-3-642-37765-5_9.
URI
https://scholars.duke.edu/individual/pub1534108
Source
crossref
Published Date
Start Page
229
End Page
257
DOI
10.1007/978-3-642-37765-5_9

Towards the design of a peptide mimetic HIV vaccine targeting the viral fusion machinery

Authors
Pessi, A; Bianchi, E; Geleziunas, R; Lennard, S; Luftig, M; Ingallinella, P; Finotto, M; Hrin, R; Joyce, J; Liang, X; Citron, M; Cortese, R; Barbato, G; Carfi, A; Kim, PS; Hazuda, D; Shiver, J; Miller, MD
MLA Citation
Pessi, A., et al. “Towards the design of a peptide mimetic HIV vaccine targeting the viral fusion machinery.” Journal of Peptide Science, vol. 12, 2006, pp. 101–101.
URI
https://scholars.duke.edu/individual/pub1532532
Source
wos-lite
Published In
Journal of Peptide Science : an Official Publication of the European Peptide Society
Volume
12
Published Date
Start Page
101
End Page
101

Time-resolved transcriptomes reveal diverse B cell fate trajectories in the early response to Epstein-Barr virus infection.

Epstein-Barr virus infection of B lymphocytes elicits diverse host responses via well-adapted transcriptional control dynamics. Consequently, this host-pathogen interaction provides a powerful system to explore fundamental processes leading to consensus fate decisions. Here, we use single-cell transcriptomics to construct a genome-wide multistate model of B cell fates upon EBV infection. Additional single-cell data from human tonsils reveal correspondence of model states to analogous in vivo phenotypes within secondary lymphoid tissue, including an EBV+ analog of multipotent activated precursors that can yield early memory B cells. These resources yield exquisitely detailed perspectives of the transforming cellular landscape during an oncogenic viral infection that simulates antigen-induced B cell activation and differentiation. Thus, they support investigations of state-specific EBV-host dynamics, effector B cell fates, and lymphomagenesis. To demonstrate this potential, we identify EBV infection dynamics in FCRL4+/TBX21+ atypical memory B cells that are pathogenically associated with numerous immune disorders.
Authors
SoRelle, ED; Dai, J; Reinoso-Vizcaino, NM; Barry, AP; Chan, C; Luftig, MA
MLA Citation
SoRelle, Elliott D., et al. “Time-resolved transcriptomes reveal diverse B cell fate trajectories in the early response to Epstein-Barr virus infection.Cell Rep, vol. 40, no. 9, Aug. 2022, p. 111286. Pubmed, doi:10.1016/j.celrep.2022.111286.
URI
https://scholars.duke.edu/individual/pub1534943
PMID
36044865
Source
pubmed
Published In
Cell Reports
Volume
40
Published Date
Start Page
111286
DOI
10.1016/j.celrep.2022.111286

Research Areas:

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
epstein-barr virus