Professor of Immunology and Chair
Cornell University College of Veterinary Medicine
C5 171 Veterinary Medical Center
PhD (Cornell University)
Dr. August assumed his position as Professor and Chair of the Department of Microbiology and Immunology in July 2010. 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 Post-Doctoral fellow at The Rockefeller University with the late Hidesaburo Hanafusa. His research program has maintained continuous funding from the National Institutes of Health for research on regulation of T cell activation and the development of lung immune responses.
See him talk about his researcha and Cornell experience on the Cornell Portraits of Extraordinary People: "Targeting asthma in animals and humans".
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 nonreceptor TKs.
Regulation of T cell activation, differentiation and allergic asthma induction 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 have T-cell defects, including reduced intracellular calcium increases during T cell activation and defective Th2 cytokine production. 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 in vitro and in vivo, using the Th2 mediated disease allergic asthma as a model. Our data indicate that Itk controls the development of allergic asthma by regulating the development of Th2 responses, but also by regulating the ability of T cells to migrate into the lung.
Regulation of T cell development by Tec family kinases
We have shown that in the absence of Itk, CD4+ and CD8+ T cells that have naïve phenotype are significantly reduced. By contrast, CD4+ and CD8+ T cells with a memory phenotype remain intact. 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. These cells have independent signaling requirements for development compared to traditional naïve T cells. 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 function and behavior of this population of these innate memory T cells.
We have also discovered that Itk regulates the development of a unique population of gd T cells. These T cells carry the CD4 and NK1.1 markers and have properties of NKT cells. They are able to rapidly secrete IL-4, and can induce B cell class switch to IgE. These cells may be critical regulators of Th2 responses and allergies.
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 implicates 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.
Dr. August is a member of the following Graduate Fields:
Chavez Carter, Graduate Student
Weishan Huang, Postdoctoral Associate
Autum (Ah-Reum) Jeong, Intern
Sonia Mohinta, Postdoctoral Associate
Kindra Stokes, Graduate Student
Amie Wood, Research Support Specialist
Shengli Hao (California Institute of Technology)
Angela Fischer (Johns Hopkins University School of Medicine)
Nawel Mahrour (Stowers Institute for Medical Research)
Jason Mercer (Merz Pharmaceuticals)
Melanie Ragin (Director, Graduate Program in Public Health, Fort Valley State University, GA)
Jianfang Hu (Scripps Research Institute)
Elizabeth Walsh (NIAID, NIH)
Nisibeta Sahu (Mass. Gen. Hosp/Harvard Medical School)
J. Luis Morales (The Pennsylvania State University)
Qian Qi (Stanford University)
Yuting Bai (Pennsylvania State University)
Mankit Law (University of North Carolina Chapel Hill)
YongChan (Chanie) Lee (Memorial Sloan-Kettering Cancer Center)
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.
Pinkerton, M., Chinchilli, V., Banta, E., Craig, T., August, A., Bascom, R., Cantorna, M., Harvill, E., Ishmael, F.T. (2013). Differential expression of microRNAs in exhaled breath condensates of patients with asthma, patients with chronic obstructive pulmonary disease, and healthy adults. J. Allergy Clin. Immunol. 132:217-219.
Kannan, A.K., Sahu, N., Mohanan, S., Mohinta, S., A. August. (2013). IL-2-inducible T-cell kinase modulates TH2-mediated allergic airway inflammation by suppressing IFN-γ in naive CD4+ T cells. J. Allergy Clin. Immunol. 2013 Jun 12. Epub.
Walsh, E. R., J. Thakar, F. Huang, K. Stokes, R. Albert and A. August. (2011). Computational and experimental analysis reveals a requirement for IL-13 production by eosinophils for the development of allergic airway responses. J. Immunol. 186:2936-2949.
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.
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.