Lee J. Quinton, Ph.D.
Associate Professor of Medicine and Pathology
College Education: University of Southern Mississippi, B.S., 1999
Graduate School: Louisiana State University Health Sciences Center, Ph.D., 2003
- Louisiana State University Health Sciences Center, 2004 (Pulmonary Host Defense. Gregory J. Bagby Ph.D. and Steve Nelson M.D.)
- Harvard School of Public Health, 2005-2008 (Pulmonary Host Defense, Joseph P. Mizgerd, Sc.D.)
- The acute phase response
- Cytokine regulation
- Acute lung injury
Lung infections account for a tremendous burden of disease, representing the most frequent cause of infection-related deaths and a common cause of acute lung injury. The innate immune response is critical for the prevention of lower respiratory tract infections. Yet, this response must be tightly regulated, such that adequate host defenses do not result in inflammatory lung injury.
Our long-term goal is to elucidate intra- and extra-pulmonary signaling events required for an immune response that is both effective and balanced. The local response to lung infections includes neutrophil recruitment, expression of soluble mediators such as cytokines, and the extravasation of plasma constituents from the vascular space into the alveolar space. The result is an inflammatory milieu and cellular composition that promotes local immune responsiveness. This physiologic transition within the lung, however, occurs in tandem with a systemic acute phase response (APR), typified by altered circulating levels of acute phase proteins (APPs). While the APR has long been recognized as a useful biomarker of disease progression during pneumonia, the collective impact of APPs on inflammation and host defense are unknown. We have previously shown that the cytokines TNF-alpha, IL-1, and IL-6, which are critical for maximal host defense during pneumonia, are also essential for the activation of downstream transcription factors and the expression of APPs in the liver. Therefore, the hepatic APR may be a systemic conduit through which select cytokines promote the immune response to lung infection. Understanding how APPs and other extra-pulmonary factors integrate with local responses in the lung to promote immunity and tissue protection during pneumonia will help to identify novel prognostic indicators and therapeutics for this important disease.
In addition to the acute phase response, our laboratory is also interested in local factors controlling innate immunity and inflammation within the airspaces of infected lungs. We have previously shown that signaling downstream of the transcription factor STAT3 is essential for tissue protection during pneumonia. We are now particularly interested in the degree to which leukemia inhibitory factor (LIF), a STAT3-signaling cytokine, is responsible for calibrating acute pulmonary inflammation during pneumonia.
Selected Publications (since 2011):
- Quinton LJ and Mizgerd JP (2014) Dynamics of lung defense in pneumonia: resistance, resilience, and remodeling. Annual Reviews in Physiology (In Press)
- Alfara VY, Goldblatt DL, Valverde GR, Munsell M, Quinton LJ, Walker AK, Dantzer R, Varadhachary A, Scott BL, Evans SE, Tuvim MJ, and Dickey BF (2014) Safety, tolerability, and biomarkers of the treatment of mice with aerosolized Toll-like receptor ligands. Frontiers in Pharmacology 5:8
- Yamamoto K, Ahyi AN, Pepper-Cunningham ZC, Ferrari JD, Willson AA, Jones MR, Quinton LJ, and Mizgerd JM (2013) Roles of lung epithelium in neutrophil recruitment during pneumococcal pneumonia. American Journal of Respiratory Cell and Molecular Biology 50:253-62
- Ahyi AN, Quinton LJ, Jones MR, Ferrari JD, Pepper-Cunningham ZA, Mella JR, Remick DG, and Mizgerd JP (2013) Roles of STAT3 in protein secretion pathway during the acute phase response. Infection and Immunity 81(5): 1644-53
- Jones MR, Blahna MT, Kozlowski E, Matsuura KY, Ferrari JD, Morris AS, Powers JT, Daley GQ, Quinton LJ, and Mizgerd JP (2012) Zcchc11 uridylates mature miRNAs to enhance neonatal IGF-1 expression, growth, and survival. PLoS Genetics 8(11): e1003105
- Quinton LJ (2012) Evaluating the NET influence of inflammation on pneumonia biology. American Journal of Respiratory and Critical Care Medicine 186(10): 943-4
- Yamamoto K, Ferrari JD, Cao Y, Ramirez MI, Jones MR, Quinton LJ, and Mizgerd JP (2012) Type I alveolar epithelial cells mount innate immune responses during pneumococcal pneumonia. Journal of Immunology 189(5): 2450-9
- Quinton LJ (corresponding author), Mizgerd JP, Hilliard KL, Jones MR, Kwon CY, and Allen E (2012) Leukemia inhibitory factor signaling is required for lung protection during pneumonia. Journal of Immunology 188 (12): 6300-8
- Quinton LJ (co-corresponding author), Blahna MT, Jones MR, Allen E, Hilliard KL, Ferrari JD, Zhang X, Sabharwal V, Algul H, Akira S, Schmid RM, Pelton SI, Spira A, and Mizgerd JP (2012) Combined hepatocyte-specific targeting of NF-κB RelA and STAT3 abrogates the acute phase response in mice. Journal of Clinical Investigation 122 (5): 1758-63
- Quinton LJ (2012) GM-CSF: A double dose of protection during pneumonia. American Journal of Physiology: Lung Cellular and Molecular Biology 302 (5): L445-6
- Blahna MT, Jones MR, Quinton LJ, Matsuura KY, and Mizgerd JP (2011) The terminal uridyltransferase enzyme zinc finger CCHC domain containing 11 (ZCCHC11) promotes cellular proliferation independent of its uridyltransferase activity. Journal of Biological Chemistry 286 (49): 42381-9
- Zamjahn J, Quinton LJ, Mack J, Frevert C, Nelson S, and Bagby GJ (2011) Differential flux of macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant from the lung after intrapulmonary delivery. American Journal of Physiology: Lung Cellular and Molecular Biology 301: L568-74
- Pittet LA, Quinton LJ, Yamamoto K, Robson BE, Ferrari JD, Algul H, Schmid RM, and Mizgerd JP (2011) Earliest innate immune responses require macrophage RelA during pneumococcal pneumonia. American Journal of Respiratory Cellular and Molecular Biology 45 (3): 573-81
- Quinton LJ and Mizgerd JP (2011) NF-KB and STAT3 signaling hubs for innate immunity. Cell and Tissue Research 343 (1): 153-65
- Mechanisms of the hepatic acute phase response during bacterial pneumonia
- Alveolar epithelial STAT3, IL-6 family cytokines, and host defense during Escherichia coli pneumonia
- Functions and regulation of NF-kB RelA during pneumococcal pneumonia