Education & Training
- Ph.D., Cell and Molecular Biology, Duke University, 2003
Aujla SJ, Alcorn JF. T(H)17 cells in asthma and inflammation. Biochim Biophys Acta. 2011 Nov;1810(11):1066-79. Epub 2011 Feb 21. Review.
Kudva A, Scheller EV, Robinson KM, Crowe CR, Choi SM, Slight SR, Khader SA, Dubin PJ, Enelow RI, Kolls JK, Alcorn JF. Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice. J Immunol. 2011 Feb 1;186(3):1666-74. Epub 2010 Dec 22.
Alcorn JF, Ckless K, Brown AL, Guala AS, Kolls JK, Poynter ME, Irvin CG, van der Vliet A, Janssen-Heininger YM. Strain-dependent activation of NF-kappaB in the airway epithelium and its role in allergic airway inflammation. Am J Physiol Lung Cell Mol Physiol. 2010 Jan;298(1):L57-66. Epub 2009 Nov 6.
Crowe CR, Chen K, Pociask DA, Alcorn JF, Krivich C, Enelow RI, Ross TM, Witztum JL, Kolls JK. Critical role of IL-17RA in immunopathology of influenza infection. J Immunol. 2009 Oct 15;183(8):5301-10. Epub 2009 Sep 25.
McKinley L, Alcorn JF, Peterson A, Dupont RB, Kapadia S, Logar A, Henry A, Irvin CG, Piganelli JD, Ray A, Kolls JK. TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J Immunol. 2008 Sep 15;181(6):4089-97.
The Alcorn laboratory is focused on T cell immunity, host defense, epithelial cell biology, and lung physiology. A primary laboratory focus is on Influenza infection and the host defense mechanisms of T helper (TH) 17 cells. Our laboratory has recently shown that the TH17 effector cytokines IL-17 and IL-22 are required for host defense against a variety of extracellular pathogens. Recent studies in the lab are focused on how preceding Influenza infection suppresses the ability of the lung to respond to secondary bacterial infections. We have shown that Influenza inhibits TH17 activation upon secondary challenge with MRSA resulting in attenuated clearance. A primary cause of mortality in human Influenza infection is co-infection with MRSA. Our data suggest an adaptive immune mechanism involved in increased susceptibility following viral infection. In addition to these studies we are interested in lung remodeling during resolution of Influenza infection. We have demonstrated that TH17 cytokines regulate epithelial repair and lung remodeling. These data may provide mechanistic insight into interstitial lung diseases such as IPF.
The Alcorn laboratory is also working on the immunologic mechanisms of severe and steroid insensitive asthma, which represent a significant source of morbidity and mortality in the western world. Specifically, we are interested in the mechanism by which T cells promote airway hyper-reactivity in the presence or absence of airway inflammation. Our current focus combines mouse models of human lung disease with translational studies utilizing our significant access to asthma samples here at Children’s Hospital of Pittsburgh. To carry out these analyses, we employ techniques in molecular cell biology, genomics, and lung physiology. Our group has recently identified the TH17 cell subset as playing a key role in severe asthma. TH17 cells promote steroid resistant allergic airway disease in mice, characterized by pulmonary neutrophil accumulation. We have recently shown that sputum samples from severe asthmatics with high percentages of neutrophilic inflammation have elevated TH17 pathway cytokines. These data suggest that TH17 cells may be critical for pathogenesis in this subset of asthmatics. In addition to these studies, our group is interested in the apparent disconnect between the degree of inflammation and airway hyper-reactivity in both asthmatics and animal models. Our focus relates to the ability of TH cells to drive airway hyper-reactivity independent of inflammation. Our group’s goal is to model human disease, as best as possible, and elucidate novel mechanisms of disease pathogenesis.