Michael Dee Gunn, MD

Professor of Medicine
Professor in Immunology
Associate Professor in Pathology
Campus mail 346 Sands Bldg, Durham, NC 27710
Phone (919) 681-0840
Email address michael.gunn@duke.edu

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, and the cell type that induces neuronal injury in Alzheimer's disease.  Our current work continues these basic studies while applying our findings to models of human disease. 

Current Research 

Identification and characterization of inflammatory cell populations in models of human disease – We have developed advanced methods of flow cytometric analysis that allows us to quantify and fully characterize all inflammatory cell types in murine and human tissues.  Using these methods, we are working to identify the cells that mediate a variety of immune pathologies.  Examples include the identification of immune-stimulatory and immune-suppressive cell types in brain tumors, identification of the cells that induce vascular changes pulmonary hypertension, and characterization of the inflammatory response to a variety of infectious pathogens.

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 testing this vaccine in various preclinical tumor models including melanoma and glioblastoma and will soon be advancing it to initial human clinical trials.

Treatment of Acute Lung Injury – We have identified the first small molecule pharmacologic agent that is effective in reducing respiratory dysfunction, vascular leak, tissue injury, and mortality during Acute Lung Injury.  We are currently validating this agent in animal models of chemical-induced ALI and testing its efficacy in reducing ALI caused by other agents such as influenza and smoke inhalation.  We hope to develop this agent as the first effective pharmacologic treatment for ALI in humans.

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 testing the use of our antibodies in a novel diagnostic assay platform to develop point-of-care assays for the diagnosis of infections by agents such as Zika virus, Dengue virus, Salmonella typhi, and Aspergillus fumigatus.

Education and Training

  • Fellowship in Cardiology, Cardiology, University of California - San Francisco, 1197
  • Internship and Residency, Internal Medicine, Parkland Health & Hospital System, 1197
  • M.D., UT Southwestern Medical School, 1983

Publications

Tighe, RM, Jiang, D, Gunn, MD, and Noble, PW. "Arginase-1 Expression in CXCR3 Knockout Mice Identifies Alternatively Activated Macrophages after Non-Infectious Lung Injury." AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 179 (2009).

Scholars@Duke

Schreiber, O, Steinwede, K, Ding, N, Srivastava, M, Maus, R, Länger, F, Prokein, J, Ehlers, S, Welte, T, Gunn, MD, and Maus, UA. "Mice that overexpress CC chemokine ligand 2 in their lungs show increased protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin." J Infect Dis 198, no. 7 (October 1, 2008): 1044-1054.

PMID
18694332
Full Text

Lipes, BD, Chen, Y-H, Ma, H, Staats, HF, Kenan, DJ, and Gunn, MD. "An entirely cell-based system to generate single-chain antibodies against cell surface receptors." J Mol Biol 379, no. 2 (May 30, 2008): 261-272.

PMID
18455737
Full Text

Kanda, H, Newton, R, Klein, R, Morita, Y, Gunn, MD, and Rosen, SD. "Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs." Nat Immunol 9, no. 4 (April 2008): 415-423.

PMID
18327261
Full Text

Lin, KL, Suzuki, Y, Nakano, H, Ramsburg, E, and Gunn, MD. "CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality." J Immunol 180, no. 4 (February 15, 2008): 2562-2572.

PMID
18250467
Scholars@Duke

Winter, C, Taut, K, Srivastava, M, Länger, F, Mack, M, Briles, DE, Paton, JC, Maus, R, Welte, T, Gunn, MD, and Maus, UA. "Lung-specific overexpression of CC chemokine ligand (CCL) 2 enhances the host defense to Streptococcus pneumoniae infection in mice: role of the CCL2-CCR2 axis." J Immunol 178, no. 9 (May 1, 2007): 5828-5838.

PMID
17442967
Scholars@Duke

Grinnan, D, Sung, S-S, Dougherty, JA, Knowles, AR, Allen, MB, Rose, CE, Nakano, H, Gunn, MD, Fu, SM, and Rose, CE. "Enhanced allergen-induced airway inflammation in paucity of lymph node T cell (plt) mutant mice." J Allergy Clin Immunol 118, no. 6 (December 2006): 1234-1241.

PMID
17157652
Full Text

Hollingsworth, JW, Whitehead, GS, Lin, KL, Nakano, H, Gunn, MD, Schwartz, DA, and Cook, DN. "TLR4 signaling attenuates ongoing allergic inflammation." J Immunol 176, no. 10 (May 15, 2006): 5856-5862.

PMID
16670292
Scholars@Duke

Wang, L, Han, R, Lee, I, Hancock, AS, Xiong, G, Gunn, MD, and Hancock, WW. "Permanent survival of fully MHC-mismatched islet allografts by targeting a single chemokine receptor pathway." J Immunol 175, no. 10 (November 15, 2005): 6311-6318.

PMID
16272282
Scholars@Duke

Suvarna, S, Rauova, L, McCracken, EKE, Goss, CM, Sachais, BS, McKenzie, SE, Reilly, MP, Gunn, MD, Cines, DB, Poncz, M, and Arepally, G. "PF4/heparin complexes are T cell-dependent antigens." Blood 106, no. 3 (August 1, 2005): 929-931.

PMID
15845897
Full Text

Pages