Liang, J, Jung, Y, Tighe, RM, Xie, T, Liu, N, Leonard, M, Gunn, MD, Jiang, D, and Noble, PW. "A macrophage subpopulation recruited by CC chemokine ligand-2 clears apoptotic cells in noninfectious lung injury." Am J Physiol Lung Cell Mol Physiol 302, no. 9 (May 1, 2012): L933-L940.
Michael Dee Gunn, MD
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.
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.
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
Cain, DW, and Gunn, MD. "NUR who? An orphan transcription factor holds promise for monomaniacs. (Published online)" Nat Immunol 12, no. 8 (July 19, 2011): 727-729.
Lin, KL, Sweeney, S, Kang, BD, Ramsburg, E, and Gunn, MD. "CCR2-antagonist prophylaxis reduces pulmonary immune pathology and markedly improves survival during influenza infection." J Immunol 186, no. 1 (January 1, 2011): 508-515.
Nakano, H, Lin, KL, Yanagita, M, Charbonneau, C, Cook, DN, Kakiuchi, T, and Gunn, MD. "Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responses." Nat Immunol 10, no. 4 (April 2009): 394-402.
Chen, Y-H, Lipes, BD, Kenan, DJ, Staats, HF, and Gunn, MD. "Identification of recombinant antibodies against multiple distinct toll-like receptors by homolog mining a single immune scFv phage library." J Immunol Methods 340, no. 2 (January 30, 2009): 144-153.
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.
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.
Nakano, H, Yanagita, M, and Gunn, MD. "CD11c(+)B220(+)Gr-1(+) cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells." J Exp Med 194, no. 8 (October 15, 2001): 1171-1178.
Mori, S, Nakano, H, Aritomi, K, Wang, CR, Gunn, MD, and Kakiuchi, T. "Mice lacking expression of the chemokines CCL21-ser and CCL19 (plt mice) demonstrate delayed but enhanced T cell immune responses." J Exp Med 193, no. 2 (January 15, 2001): 207-218.
Gunn, MD, Kyuwa, S, Tam, C, Kakiuchi, T, Matsuzawa, A, Williams, LT, and Nakano, H. "Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization." J Exp Med 189, no. 3 (February 1, 1999): 451-460.
Gunn, MD, Ngo, VN, Ansel, KM, Ekland, EH, Cyster, JG, and Williams, LT. "A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1." Nature 391, no. 6669 (February 19, 1998): 799-803.
Gunn, MD, Tangemann, K, Tam, C, Cyster, JG, Rosen, SD, and Williams, LT. "A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes." Proc Natl Acad Sci U S A 95, no. 1 (January 6, 1998): 258-263.