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

Yu, Y-RA, Hotten, DF, Malakhau, Y, Volker, E, Ghio, AJ, Noble, PW, Kraft, M, Hollingsworth, JW, Gunn, MD, and Tighe, RM. "Flow Cytometric Analysis of Myeloid Cells in Human Blood, Bronchoalveolar Lavage, and Lung Tissues." American Journal of Respiratory Cell and Molecular Biology 54, no. 1 (January 2016): 13-24.

PMID
26267148
Full Text

Kan, MJ, Lee, JE, Wilson, JG, Everhart, AL, Brown, CM, Hoofnagle, AN, Jansen, M, Vitek, MP, Gunn, MD, and Colton, CA. "Arginine deprivation and immune suppression in a mouse model of Alzheimer's disease." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience 35, no. 15 (April 2015): 5969-5982.

PMID
25878270
Full Text

Mitchell, DA, Batich, KA, Gunn, MD, Huang, M-N, Sanchez-Perez, L, Nair, SK, Congdon, KL, Reap, EA, Archer, GE, Desjardins, A, Friedman, AH, Friedman, HS, Herndon, JE, Coan, A, McLendon, RE, Reardon, DA, Vredenburgh, JJ, Bigner, DD, and Sampson, JH. "Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients." Nature 519, no. 7543 (March 11, 2015): 366-369.

PMID
25762141
Full Text

Yu, YA, Kan, MJ, Hotten, DF, Mao, L, Piantadosi, CA, and Gunn, MD. "Vascular Remodeling Macrophages Arise From Resident Monocytes, Sense Hypoxia Via Hypoxia-Induced Factor-1 alpha (hif-1 alpha), And mediate Hypoxia-Induced Pulmonary Arterial Hypertension." 2015.

Scholars@Duke

Yu, Y, Hotten, D, Birukova, A, Volker, E, Ghio, AJ, Noble, PW, Kraft, M, Hollingsworth, JW, Gunn, MD, and Tighe, RM. "Flow Cytometry Of Human Bronchoalveolar Lavage Fluid And Lung Tissue Identifies Interstitial Macrophages." 2015.

Scholars@Duke

Martinu, T, Gowdy, KM, Nugent, JL, Sun, J, Kinnier, CV, Nelson, ME, Lyes, MA, Kelly, FL, Foster, WM, Gunn, MD, and Palmer, SM. "Role of C-C motif ligand 2 and C-C motif receptor 2 in murine pulmonary graft-versus-host disease after lipopolysaccharide inhalations." American Journal of Respiratory Cell and Molecular Biology 51, no. 6 (December 2014): 810-821.

PMID
24921973
Full Text

St John, AL, Ang, WXG, Huang, M-N, Kunder, CA, Chan, EW, Gunn, MD, and Abraham, SN. "S1P-Dependent trafficking of intracellular yersinia pestis through lymph nodes establishes Buboes and systemic infection." Immunity 41, no. 3 (September 2014): 440-450.

PMID
25238098
Full Text

Sampson, J, Mitchell, DA, Batich, KA, Snyder, D, Xie, W, Reap, E, Cui, X, Sanchez-Perez, L, Archer, GE, Nair, SK, and Gunn, MD. "RANDOMIZATION OF PATIENTS WITH GLIOBLASTOMA TO VACCINE SITE PRE-CONDITIONING WITH TETANUS-DIPHTHERIA TOXOID SYSTEMICALLY ENHANCES MIGRATION AND THERAPEUTIC EFFECT OF CYTOMEGALOVIRUS PP65-PULSED DENDRITIC CELL VACCINE IN A MIP-1α-DEPENDENT FASHION." England. July 2014.

PMID
25165316
Full Text

Cain, DW, O'Koren, EG, Kan, MJ, Womble, M, Sempowski, GD, Hopper, K, Gunn, MD, and Kelsoe, G. "Identification of a tissue-specific, C/EBPβ-dependent pathway of differentiation for murine peritoneal macrophages." J Immunol 191, no. 9 (November 1, 2013): 4665-4675.

PMID
24078688
Full Text

O'Koren, EG, Hogan, BLM, and Gunn, MD. "Loss of basal cells precedes bronchiolitis obliterans-like pathological changes in a murine model of chlorine gas inhalation." American Journal of Respiratory Cell and Molecular Biology 49, no. 5 (November 2013): 788-797.

PMID
23742075
Full Text

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