Avery August, PhD
Department of Microbiology and Immunology
Professor of Immunology
Department of Microbiology and Immunology
Cornell University College of Veterinary Medicine
C5 117 Veterinary Medical Center
Ithaca, NY 14853
Regulation of immune response by intracellular signaling events.
We are interested in the role of Tyrosine Kinases (TKs) in regulating the immune response, with the goal of using this information to manipulate immune responses. We are specifically interested in the Tec families of non-receptor TKs.
Regulation of T cell activation, differentiation and regulation of inflammation and memory by Tec family kinases
Itk is a member of the Tec family of tyrosine kinases that is activated downstream of the T cell receptor, or chemokine receptors. Mice lacking Itk exhibit defects in T-cell development, as well as T cell differentiation. Understanding the specific downstream activities of these kinases is crucial to understanding how they impact lymphoid activation and development. We are currently pursuing the signaling pathways regulated by Tec family kinases that regulate the differentiation and function of Th1, Th2, Th17, and Foxp3+ and Foxp3- Type 1 regulatory T cells. We are also currently pursuing the signaling pathways regulated by Tec family kinases that regulate the development of CD8+ T cell memory in response to infection, as well as other immune processes. We are particularly interested in the function of these cells in lung inflammatory diseases, including allergic asthma.
Regulation of Innate T cell development by Tec family kinases
We have shown that in the absence of Itk, results in the development of CD4+ and CD8+ T cells a memory phenotype, and require IL4 for their development,. These memory phenotype T cells carry preformed message for IFN gamma, and can rapidly produce this cytokine in response to stimulation. These cells are able to effectively respond to infection with L. monocytogenes or exposure to LPS by secretion of IFN gamma. We have termed these cells innate memory T cells for their proposed role in both the early and adaptive immune response. We are continuing to study the development and function of this population of these innate memory T cells.
Regulation of Mast cell activation and function by Tec family kinases
Itk is also expressed in mast cells, and has been shown to be activated when IgE interacts with the receptor for IgE (FcepsilonR) in these cells. Our experiments have examined the role of Itk and the relate kinase Btk in regulating the response of these cells to stimulation via the FcepsilonR. These experiments have implications for the control of allergic responses, as well as those disease in which mast cells play a critical role.
Regulation of allergic airway inflammation by eosinophils
The presence of eosinophils in patients in asthma has long been recognized. However, their specific role in this disease is unclear. It is even unclear whether they are required for the development of this disease as the evidence is mixed. We are interested in defining the role of these cells in this disease. Using a mouse model of this disease, we examining the role of these cells, and the mechanism by which they regulate T cell responses in the lung during the development of allergic asthma.
BS (Medical Technology, California State University at Los Angeles)
PhD (Weill Cornell Graduate School of Medical Sciences of Cornell University)
Dr. August is Professor and former Chair of the Department of Microbiology and Immunology. He is currently HHMI Professor and Vice provost for Academic Affairs. His previous position was as Distinguished Professor of Immunology in the Department of Veterinary & Biomedical Sciences, and Director of the Center for Molecular Immunology & Infectious Disease, at The Pennsylvania State University at University Park, where he started as an Assistant Professor in 1999. He received a B.S. degree in Medical Technology from the California State University at Los Angeles, and a Ph.D. degree in Immunology from the Weill Cornell Graduate School of Medical Sciences. He was a Postdoctoral fellow at The Rockefeller University with the late Hidesaburo Hanafusa. See him talk about his research and Cornell experience on the Cornell Portraits of Extraordinary People: "Targeting asthma in animals and humans".
W. Huang, S. Solouki, N. Koylass, and A. August. “ITK signaling via IRF4 regulates the development and function of type 1 regulatory T cells” (2017) Nature Comm. 8:15871.
R.P. Panganiban, Y. Wang, J. Howrylak, V.M. Chinchilli, T.J. Craig, A. August, F.T Ishmael. “Circulating microRNAs as biomarkers in patients with allergic rhinitis and asthma.” J Allergy Clin Immunol. (2016) 137:1423-32.
W. Huang, J.L. Morales, V.P. Gazivoda, and A. August. “Non-receptor tyrosine kinases ITK and BTK negatively regulate mast cell pro-inflammatory responses to lipopolysaccharide” (2016) J Allergy Clin Immunol. 137:1197-205.
A. Kannan, Y-C. Lee, Q. Qi, W. Huang, A.-R. Jeong, S. Ohnigian, and A. August. “Requirement for Itk kinase activity for Th1, Th2, Th17 and iNKT cell cytokine production revealed by an allele sensitive mutant” (2015) Eur. J. Immunol. 45:2276-85.
M. Law, Y-C. Lee, J.L. Morales, G. Ning, W. Huang, J. Pabon, A.K. Kannan, A.-R. Jeong, A. Wood, C. Carter, J. Song, S. Mohinta, and A. August. “Cutting Edge: Drebrin regulated actin dynamics regulates IgE-dependent mast cell activation and allergic responses in mice” (2015) J. Immunol. 95:426-30.
Huang, W., Hu, J., A. August. (2013). Cutting edge: innate memory CD8+ T cells are distinct from homeostatic expanded CD8+ T cells and rapidly respond to primary antigenic stimuli. J. Immunol. 190:2490-2494.
Gomez-Rodriguez, J., N. Sahu, R. Handon, T.S. Davidson, S.M. Anderson, M.R. Kirby, A. August, P.L. Schwartzberg. (2009). Differential expression of interleukin-17A and -17F is coupled to T cell receptor signaling via inducible T cell kinase. Immunity. 31:587-597.
Qi, Q., M. Xia, J. Hu, E. Hicks, A. Iyer, N. Xiong, A. August. (2009). Enhanced development of CD4+ gammadelta T cells in the absence of Itk results in elevated IgE production. Blood. 114:564-571.
Walsh, E.R., N. Sahu, J. Kearley, E. Benjamin, B.H. Kang, A. Humbles, A. August. (2008). Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma. J Exp Med. 205:1285-1292.