Ruth R Montgomery PhD
Associate Professor of Medicine (Rheumatology); Director, Yale CyTOF Facility
Innate Immunity; Macrophage; Neutrophil; Aging; West Nile Virus; Lyme Disease
The focus of our lab’s research is on innate immunity, specifically the interaction of macrophages, neutrophils, and dendritic cells with pathogens. We study the effect of aging and immunosuppression on immune responses and specifically on the expression and efficiency of Toll-Like receptors. In our studies from a large cohort of human subjects, we have shown that older donors express lower levels of certain TLRs and show dysregulation of immune pathways in aging.
Our studies on West Nile virus (WNV) have shown that infection attenuates the activation of macrophages and interferes with intracellular signaling pathways. We have shown dysregulation of TLR3 in macrophages from older donors infected with WNV that leads to higher expression of cytokines and which may contribute to more severe infection in the elderly. We have evaluated the contribution of macrophages and neutrophils in several murine models of WNV infection, and in a genome-wide RNAi screen to identify host factors involved in anti-viral responses.
We conducted a comprehensive examination of phagocyte killing mechanisms in Lyme disease, and we have identified components of vector saliva that inhibit PMN function through down-regulation of leukocyte integrins. In addition to our high-resolution confocal imaging studies on phagocytes, we have imaged entire Ixodes ticks (J. Exp. Med. cover image, June 2006), and intact salivary glands to demonstrate expression of a novel tick receptor for spirochete outer surface protein A, and efficient down-regulation of salivary anti-coagulants by RNAi.
I am the Director of the CyTOF facility, which houses CyTOF2 instrument from DVS Sciences. CyTOF is a mass-spec based cell analyzer which provides multi-parametric single cell data. CyTOF improves on fluorescent flow cytometry by allowing detection of a greater number of markers per sample (~30-40 instead of 4-8) without background signals, and most importantly, without overlap between signals.
- Yao, Y., R. Liu, M. S. Shin, M. Trentalange, H. Allore, A. Nassar, I. Kang, J. Pober, and R. R. Montgomery. 2014. CyTOF supports efficient detection of immune cell subsets from small samples. J. Immunol. Methods. in press, DOI: 10.1016/j.jim.2014.10.010.
- Qian, F., G. Goel, H. Meng, X. Wang, F. You, L. Devine, K. Raddassi, M. N. Garcia, K. O. Murray, C. R. Bolen, R. Gaujoux, S. S. Shen-Orr, D. Hafler, E. Fikrig, R. J. Xavier, S. H. Kleinstein, and R. R. Montgomery. 2014. Systems Immunology reveals markers of susceptibility to West Nile virus infection. Clin. Vacc. Immunol. in press, doi:10.1128/CVI.00508-14.
- Qian, F., X. Guo, X. Wang, X. Yuan, S. Chen, S. E. Malawista, L. K. Bockenstedt, H. G. Allore, and R. R. Montgomery. 2014. Reduced Bioenergetics and Toll-like Receptor 1 Function in Human Polymorphonuclear Leukocytes in Aging. Aging 6: 131-139.
- Qian, F., J. Thakar, X. Yuan, M. Nolan, K. O. Murray, W. T. Lee, S. J. Wong, H. Meng, E. Fikrig, S. H. Kleinstein, and R. R. Montgomery. 2014. Immune markers associated with host susceptibility to infection with West Nile virus. Viral immunology 27: 39-47.
- You, F., P. Wang, L. Yang, G. Yang, Y. O. Zhao, F. Qian, W. Walker, R. E. Sutton, R. R. Montgomery, R. Lin, A. Iwasaki, and E. Fikrig. 2013. ELF4 is critical for induction of type I interferon and the host antiviral response. Nat. Immunol. 14:1237-1246.
- Qian, F., L. Chung, W. Zheng, V. M. Bruno, R. P. Alexander, Z. Wang, X. Wang, S. Kurscheid, H. Zhao, E. Fikrig, M. Gerstein, M. Snyder, and R. R. Montgomery. 2013. Identification of genes critical for resistance to infection by West Nile virus using RNA-Seq analysis. Viruses 5: 1664-1681.
- Qian, F.; Bolen, C. R.; Wang, X.; Jing, C.; Fikrig, E.; Bruce, R. D.; Kleinstein, S. H.; Montgomery, R. R., Impaired TLR3-mediated interferon responses from macrophages of patients chronically infected with Hepatitis C virus. Clin. Vaccine immunol. 2013, 20, 146-155.
- Qian, F., X. Wang, L. Zhang, S. Chen, M. Piecychna, H. Allore, L. K. Bockenstedt, S. E. Malawista, R. Bucala, A. Shaw, E. Fikrig, and R. R. Montgomery. 2012. Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly. Aging Cell 11: 104-110.
- Qian, F., and R. R. Montgomery. 2012. Quantitative imaging of lineage specific Toll-like receptor mediated signaling in monocytes and dendritic cells from small samples of human blood. JoVE 62: e3741.
- Qian, F., Wang, X., Zhang, l., Lin, A., Zhao, H., Fikrig, E., and Montgomery, R.R. 2011. Impaired interferon signaling in dendritic cells from older donors infected in vitro with West Nile virus. J. Infect. Dis. 203;1415-1424.