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 Immunology

Immunology
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:

Broad immunophenotyping of the murine brain tumor microenvironment.

Here we present a 14-color flow cytometry panel for the evaluation of 13 myeloid and lymphoid populations within murine glioblastoma samples. Reagents, processing protocols, and downstream analyses were thoroughly validated and optimized to resolve the following populations: T cells (CD4, CD8, CD3), B cells (B220), NK cells (NK1.1), neutrophils (Ly6G), classical and non-classical monocytes (Ly6c, CD43), macrophages (F4/80, CD11b), microglia (CD45-lo, CD11b), and dendritic cells (DCs) (CD11c, MHC class II). In addition, this panel leaves Alexa Fluor 488/FITC open for the inclusion of fluorescent reporters or congenic marker staining.
Authors
Tomaszewski, WH; Waibl-Polania, J; Miggelbrink, AM; Chakraborty, MA; Fecci, PE; Sampson, JH; Gunn, MD
MLA Citation
Tomaszewski, W. H., et al. “Broad immunophenotyping of the murine brain tumor microenvironment.J Immunol Methods, vol. 499, Sept. 2021, p. 113158. Pubmed, doi:10.1016/j.jim.2021.113158.
URI
https://scholars.duke.edu/individual/pub1498297
PMID
34597618
Source
pubmed
Published In
J Immunol Methods
Volume
499
Published Date
Start Page
113158
DOI
10.1016/j.jim.2021.113158

Ultrasensitive point-of-care immunoassay for secreted glycoprotein detects Ebola infection earlier than PCR.

Ebola virus (EBOV) hemorrhagic fever outbreaks have been challenging to deter due to the lack of health care infrastructure in disease-endemic countries and a corresponding inability to diagnose and contain the disease at an early stage. EBOV vaccines and therapies have improved disease outcomes, but the advent of an affordable, easily accessed, mass-produced rapid diagnostic test (RDT) that matches the performance of more resource-intensive polymerase chain reaction (PCR) assays would be invaluable in containing future outbreaks. Here, we developed and demonstrated the performance of a new ultrasensitive point-of-care immunoassay, the EBOV D4 assay, which targets the secreted glycoprotein of EBOV. The EBOV D4 assay is 1000-fold more sensitive than the U.S. Food and Drug Administration-approved RDTs and detected EBOV infection earlier than PCR in a standard nonhuman primate model. The EBOV D4 assay is suitable for low-resource settings and may facilitate earlier detection, containment, and treatment during outbreaks of the disease.
Authors
Fontes, CM; Lipes, BD; Liu, J; Agans, KN; Yan, A; Shi, P; Cruz, DF; Kelly, G; Luginbuhl, KM; Joh, DY; Foster, SL; Heggestad, J; Hucknall, A; Mikkelsen, MH; Pieper, CF; Horstmeyer, RW; Geisbert, TW; Gunn, MD; Chilkoti, A
MLA Citation
Fontes, Cassio M., et al. “Ultrasensitive point-of-care immunoassay for secreted glycoprotein detects Ebola infection earlier than PCR.Sci Transl Med, vol. 13, no. 588, Apr. 2021. Pubmed, doi:10.1126/scitranslmed.abd9696.
URI
https://scholars.duke.edu/individual/pub1478004
PMID
33827978
Source
pubmed
Published In
Sci Transl Med
Volume
13
Published Date
DOI
10.1126/scitranslmed.abd9696

Th17 Immunity in the Colon Is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes.

Intestinal immunity is coordinated by specialized mononuclear phagocyte populations, constituted by a diversity of cell subsets. Although the cell subsets constituting the mononuclear phagocyte network are thought to be similar in both small and large intestine, these organs have distinct anatomy, microbial composition, and immunological demands. Whether these distinctions demand organ-specific mononuclear phagocyte populations with dedicated organ-specific roles in immunity are unknown. Here we implement a new strategy to subset murine intestinal mononuclear phagocytes and identify two novel subsets which are colon-specific: a macrophage subset and a Th17-inducing dendritic cell (DC) subset. Colon-specific DCs and macrophages co-expressed CD24 and CD14, and surprisingly, both were dependent on the transcription factor IRF4. Novel IRF4-dependent CD14+CD24+ macrophages were markedly distinct from conventional macrophages and failed to express classical markers including CX3CR1, CD64 and CD88, and surprisingly expressed little IL-10, which was otherwise robustly expressed by all other intestinal macrophages. We further found that colon-specific CD14+CD24+ mononuclear phagocytes were essential for Th17 immunity in the colon, and provide definitive evidence that colon and small intestine have distinct antigen presenting cell requirements for Th17 immunity. Our findings reveal unappreciated organ-specific diversity of intestine-resident mononuclear phagocytes and organ-specific requirements for Th17 immunity.
Authors
Huang, H-I; Jewell, ML; Youssef, N; Huang, M-N; Hauser, ER; Fee, BE; Rudemiller, NP; Privratsky, JR; Zhang, JJ; Reyes, EY; Wang, D; Taylor, GA; Gunn, MD; Ko, DC; Cook, DN; Chandramohan, V; Crowley, SD; Hammer, GE
MLA Citation
Huang, Hsin-I., et al. “Th17 Immunity in the Colon Is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes.Front Immunol, vol. 12, 2021, p. 661290. Pubmed, doi:10.3389/fimmu.2021.661290.
URI
https://scholars.duke.edu/individual/pub1471158
PMID
33995384
Source
pubmed
Published In
Frontiers in Immunology
Volume
12
Published Date
Start Page
661290
DOI
10.3389/fimmu.2021.661290

Monocytes outperform ex vivo generated dendritic cells as cellular vaccines to trigger cytotoxic T lymphocyte responses against cancer in pre-clinical models

Authors
Huang, M-N; Nicholson, LT; Batich, KA; Kopin, D; Swartz, AM; Sampson, JH; Gunn, MD
MLA Citation
URI
https://scholars.duke.edu/individual/pub1441267
Source
wos
Published In
The Journal of Immunology
Volume
202
Published Date

Brain immunology and immunotherapy in brain tumours.

Gliomas, the most common malignant primary brain tumours, remain universally lethal. Yet, seminal discoveries in the past 5 years have clarified the anatomy, genetics and function of the immune system within the central nervous system (CNS) and altered the paradigm for successful immunotherapy. The impact of standard therapies on the response to immunotherapy is now better understood, as well. This new knowledge has implications for a broad range of tumours that develop within the CNS. Nevertheless, the requirements for successful therapy remain effective delivery and target specificity, while the dramatic heterogeneity of malignant gliomas at the genetic and immunological levels remains a profound challenge.
MLA Citation
Sampson, John H., et al. “Brain immunology and immunotherapy in brain tumours.Nat Rev Cancer, vol. 20, no. 1, Jan. 2020, pp. 12–25. Pubmed, doi:10.1038/s41568-019-0224-7.
URI
https://scholars.duke.edu/individual/pub1423063
PMID
31806885
Source
pubmed
Published In
Nat Rev Cancer
Volume
20
Published Date
Start Page
12
End Page
25
DOI
10.1038/s41568-019-0224-7

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
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