Michael Gunn

Overview:

The focus of my work is on understanding how dendritic cells, monocytes, and macrophages regulate immune responses, contribute to specific disease pathologies, and can be manipulated to stimulate or inhibit specific immune responses. We are also using our knowledge of immunology to develop diagnostics and therapeutics for a variety of human diseases. 

Lab History 

The lab started with our discovery of the lymphoid chemokines, which regulate the migration of lymphocytes and dendritic cells to and within secondary lymphoid organs.  We identified the chemokine (CCL21) that mediates the entry of naïve T cells and activated dendritic cells into lymph nodes and the chemokine (CXCL13) that mediates the entry of B cells into lymphoid follicles.  Our focus then shifted to understanding how specific cell types, primarily dendritic cells, and cell migration events regulate immune responses.  We identified murine plasmacytoid dendritic cells; the cell type that causes pulmonary immune pathology during influenza infection; the dendritic cell type that stimulates Th1 immune responses; the cell type that induces neuronal injury in Alzheimer's disease, and the macrophage type that stimulates pulmonary hypertension.  Our current work continues these basic studies while applying our findings to models of human disease. 

Current Research 

Tumor immune therapeutics – We have developed a novel cellular vaccine strategy for the treatment of cancer.  This strategy is much simpler, more cost effective, more clinically feasible, and much more efficacious than classic dendritic cell vaccines.  We are now determining the mechanisms by which this vaccine induces such potent immune responses and advancing it to initial human clinical trials.

Development of recombinant antibodies as diagnostic reagents – Our lab has developed novel methods to generate recombinant single chain antibodies using phage display technology.  We are currently using these methods to generate pathogen-specific antibodies for use in diagnostic tests for a variety of human bacterial, viral, and fungal infections.  In collaboration with Duke Biomedical Engineering, we are deploying our antibodies in a novel diagnostic assay platform to develop point-of-care assays for the diagnosis of a variety of emerging pathogens.  Our recently developed point-of-care assay for Ebola virus displays a sensitivity superior to PCR at a fraction of the per assay cost.

Positions:

Professor of Medicine

Medicine, Cardiology
School of Medicine

Professor in Integrative Immunobiology

Integrative Immunobiology
School of Medicine

Associate Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1983

UT Southwestern Medical School

Internship and Residency, Internal Medicine

Parkland Health & Hospital System

Fellowship in Cardiology, Cardiology

University of California - San Francisco

Grants:

SO150005: Smartphone Enabled Point-of-care Diagnostics for Operationally Significant Pathogens

Administered By
Biomedical Engineering
Awarded By
United States Army Medical Research Acquisition Activity
Role
Co Investigator
Start Date
End Date

Role of Resident Monocytes in the Pathogenesis of Pulmonary Arterial Hypertension

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
Awarded By
National Institutes of Health
Role
Mentor
Start Date
End Date

Targeting Extracellular Histones with Novel RNA Biodrugs for the Treatment of Acute Lung Injury

Administered By
Medicine, Cardiology
Awarded By
Department of Defense
Role
Co Investigator
Start Date
End Date

Development of anti-Salmonella Single-chain Abs as serum diagnostics

Administered By
Medicine, Cardiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Generation of Zika virus-specific recombinant antibodies

Administered By
Medicine, Cardiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Allergic Asthma Responses Are Dependent on Macrophage Ontogeny.

Authors
Tighe, RM; Birukova, A; Malakhau, Y; Kobayashi, Y; Vose, AT; Chandramohan, V; Cyphert-Daly, JM; Cumming, RI; Kirshner, HF; Tata, PR; Ingram, JL; Gunn, MD; Que, LG; Yu, Y-RA
MLA Citation
Tighe, Robert M., et al. Allergic Asthma Responses Are Dependent on Macrophage Ontogeny. 16 Feb. 2023. Pubmed, doi:10.1101/2023.02.16.528861.
URI
https://scholars.duke.edu/individual/pub1566796
PMID
36824904
Source
pubmed
Published Date
DOI
10.1101/2023.02.16.528861

Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models.

D2C7-immunotoxin (IT), a dual-specific IT targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, demonstrates encouraging survival outcomes in a subset of patients with glioblastoma. We hypothesized that immunosuppression in glioblastoma limits D2C7-IT efficacy. To improve the response rate and reverse immunosuppression, we combined D2C7-IT tumor cell killing with αCD40 costimulation of antigen-presenting cells. In murine glioma models, a single intratumoral injection of D2C7-IT+αCD40 treatment activated a proinflammatory phenotype in microglia and macrophages, promoted long-term tumor-specific CD8+ T cell immunity, and generated cures. D2C7-IT+αCD40 treatment increased intratumoral Slamf6+CD8+ T cells with a progenitor phenotype and decreased terminally exhausted CD8+ T cells. D2C7-IT+αCD40 treatment stimulated intratumoral CD8+ T cell proliferation and generated cures in glioma-bearing mice despite FTY720-induced peripheral T cell sequestration. Tumor transcriptome profiling established CD40 up-regulation, pattern recognition receptor, cell senescence, and immune response pathway activation as the drivers of D2C7-IT+αCD40 antitumor responses. To determine potential translation, immunohistochemistry staining confirmed CD40 expression in human GBM tissue sections. These promising preclinical data allowed us to initiate a phase 1 study with D2C7-IT+αhCD40 in patients with malignant glioma (NCT04547777) to further evaluate this treatment in humans.
Authors
Parker, S; McDowall, C; Sanchez-Perez, L; Osorio, C; Duncker, PC; Briley, A; Swartz, AM; Herndon, JE; Yu, Y-RA; McLendon, RE; Tedder, TF; Desjardins, A; Ashley, DM; Gunn, MD; Enterline, DS; Knorr, DA; Pastan, IH; Nair, SK; Bigner, DD; Chandramohan, V
MLA Citation
Parker, Scott, et al. “Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models.Sci Transl Med, vol. 15, no. 682, Feb. 2023, p. eabn5649. Pubmed, doi:10.1126/scitranslmed.abn5649.
URI
https://scholars.duke.edu/individual/pub1564949
PMID
36753564
Source
pubmed
Published In
Sci Transl Med
Volume
15
Published Date
Start Page
eabn5649
DOI
10.1126/scitranslmed.abn5649

A Novel MHC-Independent Mechanism of Tumor Cell Killing by CD8<sup>+</sup>T Cells

Authors
Lerner, E; Woroniecka, K; D’Anniballe, V; Wilkinson, D; Lorrey, S; Waibl-Polania, J; Wachsmuth, L; Miggelbrink, A; Raj, J; Mohan, A; Cook, S; Tomaszewski, W; Cui, X; Khasraw, M; Gunn, MD; Fecci, PE
MLA Citation
Lerner, Emily, et al. “A Novel MHC-Independent Mechanism of Tumor Cell Killing by CD8+T Cells.” Cold Spring Harbor Laboratory, 3 Feb. 2023. Crossref, doi:10.1101/2023.02.02.526713.
URI
https://scholars.duke.edu/individual/pub1564931
Source
crossref
Published Date
DOI
10.1101/2023.02.02.526713

CD8 T cell mediated killing of MHC class 1 negative tumors requires antigen presenting myeloid cells and interferon gamma

Authors
Lerner, E; D'Anniballe, V; Tomaszewski, W; Perera, J; Cui, X; Waibl-Polania, J; Wilkinson, D; Gunn, MD; Fecci, PE; Woroniecka, K
MLA Citation
URI
https://scholars.duke.edu/individual/pub1572174
Source
wos-lite
Published In
Cancer Research
Volume
82
Published Date

Lessons from the pandemic: Responding to emerging zoonotic viral diseases-a Keystone Symposia report.

The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases" to discuss the successes and challenges of the COVID-19 pandemic and what lessons can be applied moving forward. Speakers focused on experiences not only from the COVID-19 pandemic but also from outbreaks of other pathogens, including the Ebola virus, Lassa virus, and Nipah virus. A general consensus was that investments made during the COVID-19 pandemic in infrastructure, collaborations, laboratory and manufacturing capacity, diagnostics, clinical trial networks, and regulatory enhancements-notably, in low-to-middle income countries-must be maintained and strengthened to enable quick, concerted responses to future threats, especially to zoonotic pathogens.
Authors
Cable, J; Fauci, A; Dowling, WE; Günther, S; Bente, DA; Yadav, PD; Madoff, LC; Wang, L-F; Arora, RK; Van Kerkhove, M; Chu, MC; Jaenisch, T; Epstein, JH; Frost, SDW; Bausch, DG; Hensley, LE; Bergeron, É; Sitaras, I; Gunn, MD; Geisbert, TW; Muñoz-Fontela, C; Krammer, F; de Wit, E; Nordenfelt, P; Saphire, EO; Gilbert, SC; Corbett, KS; Branco, LM; Baize, S; van Doremalen, N; Krieger, MA; Clemens, SAC; Hesselink, R; Hartman, D
MLA Citation
Cable, Jennifer, et al. “Lessons from the pandemic: Responding to emerging zoonotic viral diseases-a Keystone Symposia report.Ann N Y Acad Sci, vol. 1518, no. 1, Dec. 2022, pp. 209–25. Pubmed, doi:10.1111/nyas.14898.
URI
https://scholars.duke.edu/individual/pub1553512
PMID
36183296
Source
pubmed
Published In
Ann N Y Acad Sci
Volume
1518
Published Date
Start Page
209
End Page
225
DOI
10.1111/nyas.14898

Research Areas:

Acute Lung Injury
Adjuvants, Immunologic
Administration, Intranasal
Adoptive Transfer
Airway Resistance
Amino Acid Sequence
Animals
Anthrax Vaccines
Anti-Inflammatory Agents, Non-Steroidal
Antibodies, Bacterial
Antibodies, Monoclonal
Antibodies, Neutralizing
Antibody Affinity
Antibody Specificity
Antigen Presentation
Antigen-Presenting Cells
Antigens, Bacterial
Antigens, CD11b
Antigens, CD11c
Antigens, CD18
Antigens, CD44
Antigens, CD45
Apoptosis
Arachidonate 5-Lipoxygenase
Arterioles
Benzhydryl Compounds
Bleomycin
Blood Vessels
Bone Marrow Cells
Brain Injuries
Burkitt Lymphoma
CD11b Antigen
CD11c Antigen
CD18 Antigens
CD4-Positive T-Lymphocytes
Carbohydrate Sequence
Cell Adhesion
Cell Adhesion Molecules
Cell Migration Inhibition
Cell Movement
Cell Proliferation
Cells, Cultured
Central Nervous System
Chemokine CCL19
Chemokine CCL2
Chemokine CCL21
Chemokine CCL22
Chemokine CXCL12
Chemokine CXCL13
Chemokines
Chemokines, CC
Chemokines, CXC
Chemotaxis
Chemotaxis, Leukocyte
Chimerism
Chlorine
Clonal Anergy
Coronavirus Infections
CpG Islands
Cricetinae
Cysteine
DNA, Complementary
Dendritic Cells
Diclofenac
Disease Models, Animal
Drug Synergism
E-Selectin
Encephalomyelitis, Autoimmune, Experimental
Endothelium, Lymphatic
Enzyme-Linked Immunosorbent Assay
Eosinophils
Epitopes, T-Lymphocyte
Escherichia coli
Escherichia coli Infections
Female
Fibrosis
Flow Cytometry
GTP-Binding Proteins
Gene Deletion
Gene Duplication
Genetic Linkage
Graft Rejection
Graft Survival
Granulocyte-Macrophage Colony-Stimulating Factor
Heart Transplantation
Hematopoietic Stem Cell Transplantation
Histocompatibility Antigens Class II
Homeodomain Proteins
Humans
Hyaluronan Receptors
Hyperalgesia
Hypertension, Pulmonary
Immune System
Immunity, Innate
Immunoblotting
Immunoglobulin G
Immunologic Memory
Immunosuppressive Agents
In Situ Hybridization
Inflammation
Inflammation Mediators
Influenza A Virus, H1N1 Subtype
Injections, Intradermal
Injections, Spinal
Integrin alphaXbeta2
Intercellular Adhesion Molecule-1
Intercellular Signaling Peptides and Proteins
Interferon-alpha
Interleukin-1alpha
Interleukin-3
Interleukin-4
Intracellular Signaling Peptides and Proteins
Jurkat Cells
Kidney
L-Selectin
Leukocyte Common Antigens
Leukocyte Count
Leukocytes
Leukotrienes
Ligands
Lipopolysaccharides
Lung
Lymph Nodes
Lymphatic System
Lymphocyte Count
Lymphocyte Function-Associated Antigen-1
Lymphocytes
Lymphotoxin-alpha
Lysophospholipids
Macrophage Activation
Macrophages
Macrophages, Alveolar
Macrophages, Peritoneal
Male
Manganese
Mast Cells
Membrane Proteins
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Inbred Strains
Mice, Knockout
Mice, Mutant Strains
Mice, Nude
Mice, Transgenic
Molecular Sequence Data
Monocytes
Mucins
Multidrug Resistance-Associated Proteins
Multigene Family
Muramidase
Muscle, Smooth, Vascular
Muser Mentor
Myosin Heavy Chains
Neovascularization, Pathologic
Neutrophil Infiltration
Ovalbumin
Pain, Postoperative
Peroxidase
Phosphoserine
Plasma Cells
Pneumonia, Viral
Propylene Glycols
RNA, Messenger
Rats
Rats, Wistar
Receptor Protein-Tyrosine Kinases
Receptors, Antigen, T-Cell
Receptors, CCR2
Receptors, CCR7
Receptors, CXCR5
Receptors, Cell Surface
Receptors, Chemokine
Receptors, Cytokine
Receptors, G-Protein-Coupled
Receptors, Growth Factor
Receptors, Lymphocyte Homing
Receptors, Lysophospholipid
Receptors, Metabotropic Glutamate
Respiratory System
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
Serum
Skin
Sphingosine
Spleen
Sulfotransferases
Sulfur
T-Lymphocyte Subsets
T-Lymphocytes
T-Lymphocytes, Helper-Inducer
Tetradecanoylphorbol Acetate
Thiophenes
Toll-Like Receptor 4
Tumor Necrosis Factor-alpha
Tumor Suppressor Proteins
Up-Regulation
Vaccination
Vascular Endothelial Growth Factor Receptor-3
Vesicular Transport Proteins