Michael G. Brown
- Phone: 434-924-5106
- Fax: 434-924-1221
Primary Appointment
Professor, Medicine- Nephrology
Education
- BS, Biochemistry, Virginia Tech University
- PhD, Immunology, Medical College of Virginia, Virginia Commonwealth University
- Postdoc, Immunology, Mount Sinai School of Medicine
- Postdoc, Immunology, Washington University
Research Disciplines
Bioinformatics and Genomics, Biotechnology, Cancer Biology, Genetics, Immunology, Infectious Diseases/Biodefense, Microbiology, Molecular Biology
Research Interests
Natural Killer Cells, Viral Immunity, Genetic basis of host resistance to viral infection, Tumor immunity, Immune cell regulation
Research Description
We have learned that the major histocompatibility complex (MHC) exerts substantial control over NK cells, and we have developed several informative mouse models to explore this effect in much greater depth. We found that MHC class I-dependent education (also referred to as licensing), affects the capacity of NK cells to mediate virus-specific clearance, in addition to its effect on NK cell functionality. We hypothesize that licensing impacts NK-mediated responsiveness to cancer cells, as well. While the molecular basis of licensing remains poorly defined, the model systems and resources now developed in the lab provide an outstanding way to explore the basis and vital roles of NK cells in viral or tumor immunity.
Personal Statement
We have learned that the MHC exerts substantial control over NK cells, and we have developed several informative mouse models to examine this effect in greater depth. We found that MHC class I-dependent education (also referred to as licensing), affects the capacity of NK cells to mediate virus-specific clearance, in addition to its effect on NK functionality. We hypothesize that licensing impacts NK-mediated responsiveness to cancer cells. While the molecular basis of licensing is poorly defined, the model systems and resources that we have acquired and developed allow us to probe how NK cells recognize and mediate lysis of infected or malignant target cells.
Training
- Biodefense & Infectious Diseases Short-Term Training to Increase Diversity in Biomedical Sciences
- Biotechnology Training Grant
- Interdisciplinary Training Program in Immunology
Selected Publications
List of the most up-to-date publications: https://www.ncbi.nlm.nih.gov/myncbi/michael.brown.1/bibliography/public/?sortby=pubDate&sdirection=descending
2024
Annis, J. L., & Brown, M. G. (2024). Inflammation and Macrophage Loss Mark Increased Susceptibility in a Genetic Model of Acute Viral Infection-Induced Tissue Damage.. Journal of immunology (Baltimore, Md. : 1950), ji2400116. doi:10.4049/jimmunol.2400116
Wessel, R. E., Ageeb, N., Obeid, J. M., Mauldin, I., Goundry, K. A., Hanson, G. F., . . . Brown, M. G. (2024). Spatial colocalization and combined survival benefit of natural killer and CD8 T cells despite profound MHC class I loss in non-small cell lung cancer.. bioRxiv. doi:10.1101/2024.02.20.581048
Annis, J. L., Duncan, J. B. W., Billcheck, H. O., Kuzma, A. G., Crittenden, R. B., & Brown, M. G. (2024). Multiple Immune and Genetic Mechanisms Contribute to Cmv5s-Driven Susceptibility and Tissue Damage during Acute Murine Cytomegalovirus Infection.. Journal of immunology (Baltimore, Md. : 1950), 212(5), 813-824. doi:10.4049/jimmunol.2300648
2022
Cronk, J. M., Dziewulska, K. H., Puchalski, P., Crittenden, R. B., Hammarskjod, M. -L., & Brown, M. G. (2022). Altered-Self MHC Class I Sensing via Functionally Disparate Paired NK Cell Receptors Counters Murine Cytomegalovirus gp34-Mediated Immune Evasion. JOURNAL OF IMMUNOLOGY, 209(8), 1545-1554. doi:10.4049/jimmunol.2200441
Nozaki, K., Maltez, V. I., Rayamajhi, M., Tubbs, A. L., Mitchell, J. E., Lacey, C. A., . . . Miao, E. A. (2022). Caspase-7 activates ASM to repair gasdermin and perforin pores. NATURE, 606(7916), 960-+. doi:10.1038/s41586-022-04825-8
Lindsay, R. S. S., Melssen, M. M. M., Stasiak, K., Annis, J. L. L., Woods, A. N. N., Rodriguez, A. B. B., . . . Engelhard, V. H. H. (2022). NK cells reduce anergic T cell development in early-stage tumors by promoting myeloid cell maturation. FRONTIERS IN ONCOLOGY, 12. doi:10.3389/fonc.2022.1058894
2021
Cronk, J. M., Fafoutis, E., & Brown, M. G. (2021). Licensing Natural Killers for Antiviral Immunity. PATHOGENS, 10(7). doi:10.3390/pathogens10070908
2019
Gamache, A., Cronk, J. M., Nash, W. T., Puchalski, P., Gillespie, A., Wei, H., . . . Brown, M. G. (2019). Ly49R activation receptor drives self-MHC-educated NK cell immunity against cytomegalovirus infection. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 116(52), 26768-26778. doi:10.1073/pnas.1913064117
2018
Brown, M. G., Gamache, A., Nash, W. T., & Cronk, J. (2019). Natural selection for killer receptors and their MHC class I ligands: In pursuit of gene pairs that fit well in tandem. JOURNAL OF LEUKOCYTE BIOLOGY, 105(3), 489-495. doi:10.1002/JLB.2RI0818-315R
Shi, L., Li, K., Guo, Y., Banerjee, A., Wang, Q., Lorenz, U. M., . . . Krupnick, A. S. (2018). Modulation of NKG2D, NKp46, and Ly49C/I facilitates natural killer cell-mediated control of lung cancer. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 115(46), 11808-11813. doi:10.1073/pnas.1804931115
2017
Brown, M. G., & Gamache, A. (2017). Editorial: On matters of maturity, self-control, and responsiveness: inhibitory NK receptors in the driver's seat?. JOURNAL OF LEUKOCYTE BIOLOGY, 102(6), 1281-1284. doi:10.1189/jlb.1CE0717-280RR
Gillespie, A., Lee, H., Robertson, C., Cabot, M., & Brown, M. G. (2017). Genome-Wide Exome Analysis of Cmv5-Disparate Mouse Strains that Differ in Host Resistance to Murine Cytomegalovirus Infection. G3-GENES GENOMES GENETICS, 7(6), 1979-1984. doi:10.1534/g3.117.042531
Nash, W. T., Gillespie, A. L., & Brown, M. G. (2017). Murine cytomegalovirus Disrupts splenic Dendritic cell subsets via Type I Interferon-Dependent and -Independent Mechanisms. FRONTIERS IN IMMUNOLOGY, 8. doi:10.3389/fimmu.2017.00251
2016
Teoh, J. J., Gamache, A. E., Gillespie, A. L., Stadnisky, M. D., Yagita, H., Bullock, T. N. J., & Brown, M. G. (2016). Acute Virus Control Mediated by Licensed NK Cells Sets Primary CD8+ T Cell Dependence on CD27 Costimulation.. Journal of immunology (Baltimore, Md. : 1950), 197(11), 4360-4370. doi:10.4049/jimmunol.1601049
Krueger, P. D., Narayanan, S., Surette, F. A., Brown, M. G., Sung, S. -S. J., & Hahn, Y. S. (2017). Murine liver-resident group 1 innate lymphoid cells regulate optimal priming of anti-viral CD8+ T cells. JOURNAL OF LEUKOCYTE BIOLOGY, 101(1), 329-338. doi:10.1189/jlb.3A0516-225R
Gillespie, A. L., Teoh, J., Lee, H., Prince, J., Stadnisky, M. D., Anderson, M., . . . Brown, M. G. (2016). Genomic Modifiers of Natural Killer Cells, Immune Responsiveness and Lymphoid Tissue Remodeling Together Increase Host Resistance to Viral Infection. PLOS PATHOGENS, 12(2). doi:10.1371/journal.ppat.1005419
2015
Brown, M. G., & Erickson, L. D. (2015). Editorial: NK cell reaping of Tfh cells: reckless slaughter or sensible pruning?. JOURNAL OF LEUKOCYTE BIOLOGY, 98(2), 139-142. doi:10.1189/jlb.4CE0415-175R
2014
Wei, H., Nash, W. T., Makrigiannis, A. P., & Brown, M. G. (2014). Impaired NK-cell education diminishes resistance to murine CMV infection. EUROPEAN JOURNAL OF IMMUNOLOGY, 44(11), 3273-3282. doi:10.1002/eji.201444800
Nash, W. T., Teoh, J., Wei, H., Gamache, A., & Brown, M. G. (2014). Know thyself: NK-cel innibitory receptors prompt self-tolerance, education, and viral control. FRONTIERS IN IMMUNOLOGY, 5, 1-12. doi:10.3389/fimmu.2014.00175
2013
Prince, J., Lundgren, A., Stadnisky, M. D., Nash, W. T., Beeber, A., Turner, S. D., & Brown, M. G. (2013). Multiparametric Analysis of Host Response to Murine Cytomegalovirus in MHC Class I-Disparate Mice Reveals Primacy of Dk-Licensed Ly49G2+ NK Cells in Viral Control. JOURNAL OF IMMUNOLOGY, 191(9), 4709-4719. doi:10.4049/jimmunol.1301388
2012
Lundgren, A., Kim, S., Stadnisky, M. D., & Brown, M. G. (2012). Rapid discrimination of MHC class I and killer cell lectin-like receptor allele variants by high-resolution melt analysis. IMMUNOGENETICS, 64(8), 633-640. doi:10.1007/s00251-012-0630-4
Ge, Y., Brown, M. G., Wang, H., & Fu, S. M. (2012). Genetic approach to study lupus glomerulonephritis.. Methods in molecular biology (Clifton, N.J.), 900, 271-290. doi:10.1007/978-1-60761-720-4_13
2011
Carroll, V. A., Lundgren, A., Wei, H., Sainz, S., Tung, K. S., & Brown, M. G. (2012). Natural Killer Cells Regulate Murine Cytomegalovirus-Induced Sialadenitis and Salivary Gland Disease. JOURNAL OF VIROLOGY, 86(4), 2132-2142. doi:10.1128/JVI.06898-11
Stadnisky, M. D., Xie, X., Coats, E. R., Bullock, T. N., & Brown, M. G. (2011). Self MHC class I-licensed NK cells enhance adaptive CD8 T-cell viral immunity. BLOOD, 117(19), 5133-5141. doi:10.1182/blood-2010-12-324632
2010
Xie, X., Stadnisky, M. D., Coats, E. R., Rahim, M. M. A., Lundgren, A., Xu, W., . . . Brown, M. G. (2010). MHC class I Dk expression in hematopoietic and nonhematopoietic cells confers natural killer cell resistance to murine cytomegalovirus. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107(19), 8754-8759. doi:10.1073/pnas.0913126107
Lassen, M. G., Lukens, J. R., Dolina, J. S., Brown, M. G., & Hahn, Y. S. (2010). Intrahepatic IL-10 Maintains NKG2A+Ly49- Liver NK Cells in a Functionally Hyporesponsive State. JOURNAL OF IMMUNOLOGY, 184(5), 2693-2701. doi:10.4049/jimmunol.0901362