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Michael G. Brown

Michael G. Brown

Professor, Medicine- Nephrology

Primary Location
PO Box 801386
MR6, Rm 2714A
Charlottesville, Virginia 22908
Primary Phone Number
434.924.5106
Fax Number
434.924.1221
Email
[email protected]

Bio & Overview

A main goal of research in the Brown Lab centers on the genetics of host resistance to viral infection, and the role of natural killer (NK) cells in viral immunity. We aim to understand (1) how genetic variation shapes both innate and adaptive immune cell features, and how these differences further affect immune cells needed to detect and clear viral pathogens; (2) how NK cell effector function is acquired and regulated by both genetic and environmental influences; and (3) how NK responses to immune stimulation can specifically regulate adaptive immune outcomes. 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.

Academic Information

Department
Medicine- Nephrology
Academic Title
Professor of Medicine

Primary Education

  • BS, Biochemistry, Virginia Tech University, 1986
  • PhD, Immunology, Medical College of Virginia, Virginia Commonwealth University, 1993
  • Postdoc, Immunology, Mount Sinai School of Medicine, 1995
  • Postdoc, Immunology, Washington University, 2000

Other Appointments

  • Professor, Microbiology, Immunology, and Cancer Biology
  • Pathology
  • Associate Professor, Nephrology
  • Professor, Medicine- Nephrology

Other Affiliations

  • Cancer Center
  • Member, Immunology/Immunotherapy Program
  • Mentor, Microbiology
  • Resident Faculty, Beirne Carter Center for Immunology
  • MSTP
  • Professor, BIMS

Research Interests

Natural Killer Cells, Viral Immunity, Genetic basis of host resistance to viral infection, Tumor immunity, Immune cell regulation

Research Disciplines

  • Bioinformatics and Genomics
  • Biotechnology
  • Cancer Biology
  • Genetics
  • Immunology
  • Infectious Diseases/Biodefense
  • Microbiology
  • Molecular Biology

Research Opportunities

  • Cancer Biology
  • Genetics
  • Immunology
  • Infectious Diseases
  • Molecular Biology

PhD Programs

  • Experimental Pathology
  • Microbiology

Selected Publications

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