Boston University Medical Campus
Pulmonary, Critical Care, and Allergy Medicine

College Education:

Special Interests:
RESEARCH:

• Acute lower respiratory tract infection
• Cytokines
• Innate immunity
• Neutrophil recruitment and activation
• Pneumonia
• Transcriptional and post-transcriptional regulation of gene expression

Acute lower respiratory tract infections cause a terrible public health burden at present, with potential for worse in the coming years. The outcome of these infections is determined by innate immune responses (such as neutrophil recruitment and activation), necessary for host defense but also contributing to lung injury. Innate immune responses in the lungs require the coordinated expression of diverse mediators including adhesion molecules, chemokines, colony stimulating factors, and cytokines that are absent or present only at low levels in uninfected lungs, but are expressed at high levels during infection. Similar mediators are induced during most lung infections, although individual mediators can have different roles during different infections. The coordinated expression suggests programs of gene regulation. NF-kappaB transcription factors are critical to the gene expression program directing innate immunity in the lungs, with RelA inducing innate immunity genes mediating host defense and p50 counteracting this gene induction to prevent lung injury. Other transcription factors are also important, such as STAT3 which both facilitates host defense and limits lung injury. These transcription factors have cell-specific roles during infection. Finally, expression of innate immunity mediators is regulated post-transcriptionally as well. MicroRNAs target innate immunity transcripts, and miRNAs themselves are subject to modifications such as uridylation by Zcchc11 to relieve their repressive activities. An improved knowledge of the molecular mechanisms directing innate immunity in the lungs will provide new directions for preventing and curing acute lower respiratory tract infections.

Selected Publications:

1. Jones MR, Quinton LJ, Blahna MT, Neilson JR, Fu S, Ivanov AR, Wolf DA, Mizgerd JP. 2009. Zcchc11-dependent uridylation of microRNA directs cytokine expression. Nat Cell Biol 11: 1157-63
2. Quinton, LJ, MR Jones, BE Robson, JP Mizgerd. 2009. Mechanisms of the hepatic acute phase response during bacterial pneumonia. Infect Immun 77:2417-26.
3. Quinton, LJ, MR Jones, BE Robson, BT Simms, JA Whitsett, JP Mizgerd. 2008. Alveolar epithelial STAT3, IL-6 family cytokines, and host defense during Escherichia coli pneumonia. Am J Respir Cell Mol Biol 38:699-706.
4. Mizgerd, JP. 2008. Mechanisms of disease: Acute lower respiratory infection. N Engl J Med 358:716-727.
5. Quinton, LJ, MR Jones, BT Simms, MS Kogan, BE Robson, SJ Skerrett, JP Mizgerd. 2007. Functions and regulation of NF-kappaB RelA during pneumococcal pneumonia. J Immunol 178:1896-1903.
6. Jones, MR, LJ Quinton, BT Simms, MM Lupa, MS Kogan, JP Mizgerd. 2006. Roles of interleukin-6 in activation of STAT proteins and recruitment of neutrophils during Escherichia coli pneumonia. J Infect Dis 193:360-369.
7. Mizgerd, JP. 2006. Lung infection – a public health priority. PLoS Medicine 3(2):e76.

Selected Reprints:

1. Acute Lower Respiratory Tract Infection
2. Lung Infection – A Public Health Priority

Links:

Pneumonia Biology web site: http://www.bumc.bu.edu/pneumonia/