Michael Dee Gunn, MD

Professor of Medicine
Professor in Immunology
Associate Professor in Pathology
Member of the Duke Cancer Institute
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

Privratsky, JR, Zhang, J, Lu, X, Rudemiller, N, Wei, Q, Yu, Y-R, Gunn, MD, and Crowley, SD. "Interleukin 1 receptor (IL-1R1) activation exacerbates toxin-induced acute kidney injury." American Journal of Physiology Renal Physiology 315, no. 3 (September 2018): F682-F691.

PMID
29790392
Full Text

Chongsathidkiet, P, Jackson, C, Koyama, S, Loebel, F, Cui, X, Farber, SH, Woroniecka, K, Elsamadicy, AA, Dechant, CA, Kemeny, HR, Sanchez-Perez, L, Cheema, TA, Souders, NC, Herndon, JE, Coumans, J-V, Everitt, JI, Nahed, BV, Sampson, JH, Gunn, MD, Martuza, RL, Dranoff, G, Curry, WT, and Fecci, PE. "Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors." Nature Medicine 24, no. 9 (September 2018): 1459-1468.

PMID
30104766
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Tata, A, Kobayashi, Y, Chow, RD, Tran, J, Desai, A, Massri, AJ, McCord, TJ, Gunn, MD, and Tata, PR. "Myoepithelial Cells of Submucosal Glands Can Function as Reserve Stem Cells to Regenerate Airways after Injury." Cell Stem Cell 22, no. 5 (May 2018): 668-683.e6.

PMID
29656943
Full Text

Mastria, EM, Cai, LY, Kan, MJ, Li, X, Schaal, JL, Fiering, S, Gunn, MD, Dewhirst, MW, Nair, SK, and Chilkoti, A. "Nanoparticle formulation improves doxorubicin efficacy by enhancing host antitumor immunity." Journal of Controlled Release : Official Journal of the Controlled Release Society 269 (January 2018): 364-373.

PMID
29146246
Full Text

Baek, AE, Yu, Y-RA, He, S, Wardell, SE, Chang, C-Y, Kwon, S, Pillai, RV, McDowell, HB, Thompson, JW, Dubois, LG, Sullivan, PM, Kemper, JK, Gunn, MD, McDonnell, DP, and Nelson, ER. "The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells." Nature Communications 8, no. 1 (October 11, 2017): 864-null.

PMID
29021522
Full Text

Smith, J, Nicholson, L, Suwanpradid, J, Glenn, R, Gundry, J, Alagesan, P, Knape, N, Atwater, A, Gunn, M, MacLeod, A, Lefkowitz, R, and Rajagopal, S. "678 Biased CXCR3 ligands differentially alter allergic contact hypersensitivity and chemotaxis." May 2017.

Full Text

Rudemiller, NP, Patel, MB, Zhang, J-D, Jeffs, AD, Karlovich, NS, Griffiths, R, Kan, MJ, Buckley, AF, Gunn, MD, and Crowley, SD. "C-C Motif Chemokine 5 Attenuates Angiotensin II-Dependent Kidney Injury by Limiting Renal Macrophage Infiltration." The American Journal of Pathology 186, no. 11 (November 2016): 2846-2856.

PMID
27640148
Full Text

Izykowski, N, Kuehnel, M, Hussein, K, Mitschke, K, Gunn, M, Janciauskiene, S, Haverich, A, Warnecke, G, Laenger, F, Maus, U, and Jonigk, D. "Organizing pneumonia in mice and men." Journal of translational medicine 14, no. 1 (June 10, 2016): 169-.

PMID
27282780
Full Text

Tighe, RM, Li, Z, Potts, EN, Frush, S, Liu, N, Gunn, MD, Foster, WM, Noble, PW, and Hollingsworth, JW. "Erratum: Ozone inhalation promotes CX3CR1-dependent maturation of resident lung macrophages that limit oxidative stress and inflammation (Journal of Immunology (2011) 187 (4800-4808))." Journal of Immunology 196, no. 5 (March 1, 2016): 2424-.

Full Text

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

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