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
Professor in Integrative Immunobiology
Associate Professor in Pathology
Member of the Duke Cancer Institute
Education:
M.D. 1983
Internship and Residency, Internal Medicine
Fellowship in Cardiology, Cardiology
Grants:
SO150005: Smartphone Enabled Point-of-care Diagnostics for Operationally Significant Pathogens
Role of Resident Monocytes in the Pathogenesis of Pulmonary Arterial Hypertension
Targeting Extracellular Histones with Novel RNA Biodrugs for the Treatment of Acute Lung Injury
Development of anti-Salmonella Single-chain Abs as serum diagnostics
Generation of Zika virus-specific recombinant antibodies
Publications:
Allergic Asthma Responses Are Dependent on Macrophage Ontogeny.
Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models.
A Novel MHC-Independent Mechanism of Tumor Cell Killing by CD8<sup>+</sup>T Cells
CD8 T cell mediated killing of MHC class 1 negative tumors requires antigen presenting myeloid cells and interferon gamma
Lessons from the pandemic: Responding to emerging zoonotic viral diseases-a Keystone Symposia report.
Research Areas:
