Avery August, PhD
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. 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.
Regulation of production of inflammatory and anti-inflammatory cytokines by CD4+ and CD8+ T cells activation by Tec family kinases
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, and CD8+ T cells, with specific attention paid to the production of inflammatory cytokines (such as IL17A and IFNg) and anti-inflammatory cytokines (such as IL10). We use mouse models of lung and mucosal inflammatory and infectious disease, including infection with flu, and development of allergic asthma and inflammatory bowel disease, to explore this regulation. We are exploring the molecule mechanisms that drive this process.
Regulation of CD8+ T cell memory development by Tec family kinases
We are also currently pursuing the regulation of CD8+ T cell memory development by Itk. We have shown that the absence of Itk, CD8+ T cell memory development is enhanced. This enhanced memory development is seen in innate memory T cells, a process we have shown is dependent on IL4. 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. Antigen specific CD8+ T cell memory development is also enhanced in the absence of Itk and we are exploring the molecule mechanisms that drive the development of these different types of memory cells.
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".
Owen DL, Mahmud SA, Sjaastad LE, Williams JB, Spanier JA, Simeonov DR, Ruscher R, Huang W, Proekt I, Miller CN, Hekim C, Jeschke JC, Aggarwal P, Broeckel U, LaRue RS, Henzler CM, Alegre ML, Anderson MS, August A, Marson A, Zheng Y, Williams CB, Farrar MA. “Thymic regulatory T cells arise via two distinct developmental programs.” (2019) Nat Immunol. 20:195-205. doi: 10.1038/s41590-018-0289-6. Epub 2019 Jan 14.
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.