Avery August, Ph. D
Cornell University, Professor and Chair of Microbiology and Immunology
Avery August received his undergraduate degree in Medical Technology at the California State University at Los Angeles, performing research in synthesis of phospholipids for membrane biophysical studies with Prof. Phoebe Dea in the Department of Chemistry & Biochemistry. After receiving his degree, he spent a year in the Master’s Program in Biochemistry at the same institution, then entered the graduate program in Immunology at the Weill Cornell Graduate School of Medical Sciences (Cornell University) in New York City. There he worked first with Prof. David Posnett on T cell receptors associated with disease, then with Prof. Bo Dupont, with whom he did his PhD thesis. With Prof. Dupont, located at the Memorial Sloan Kettering Cancer Center, he worked on signal transduction in T cells, examining the molecular basis for the two signal hypothesis, signaling by the costimulatory molecule CD28. Among other discoveries, we were among the first to show that the CD28 costimulatory receptor activated the PI3 kinase. We were also the first to show that the Tec kinase ITK is activated by both the T cell receptor, as well as CD28. This work formed the basis for his PhD thesis in 1994.
After receiving the PhD, he took a post-doctoral fellowship in the Laboratory of Molecular Oncology with Prof. Hidesaburo Hanafusa at The Rockefeller University in New York City. Among other discoveries at this time, he was among the first to show that Tec kinases are activated by both Src kinases and PI3 kinase, and that this required the PH domains of these kinases. In addition, he was among the first to show that the breast cancer susceptible gene, BRCA1, possesses transcriptional activity. In 1997, he took a position as Scientist in the Drug Discovery unit at the R.W. Johnson Pharmaceutical Research Institute.
In 1999, he left the R.W. Johnson Pharmaceutical Research Institute for a position as Assistant Professor in the Department of Veterinary & Biomedical Sciences at the Pennsylvania State University at University Park. Here he began examining the role of ITK in the function of T cells and in disease, particularly allergic and airway inflammatory disease. He also worked on other questions, such as the role of signaling pathways in B cells that modulate the actin cytoskeleton and activate the SRF transcription factor. He showed that ITK has kinase independent activity in regulating these pathways. He subsequently showed that this kinase independent function of ITK also regulates the development of invariant NKT cells. He showed for the first time that mice lacking ITK were resistant to developing allergic airway inflammation, and that this was due both to reduced Th2 responses in the mice, as well as for the first time, reduced chemokine receptor mediated migration. Following up on these findings, he found that ITK deficient mast cells have enhanced Fc epsilon Receptor responses, while those lacking both ITK and BTK, a related Tec kinase, are completely defective. He has also determined that eosinophils play a critical role in the development of airway inflammation, in part by regulating IL13 mediated recruitment of T cells to the lung. Along with others, he has discovered that the absence of ITK affects the development of two populations of gamma delta T cells. In the first case, the absence of ITK reduces the development of skin γδ T cells bearing the Vγ3 T cell receptor (sIEL). By contrast, the absence of ITK enhances the development of a population of peripheral γδ T cells that carry Vγ1.1 and Vδ6.2/3, and secrete large amounts of IL4, which can drive the production of IgE in these mice. These cells may also be responsible for another finding he hand others have reported, the presence of T cells with innate memory phenotype in mice lacking ITK. Along the way came promotions to Associate Professor in 2004, to Professor in 2008, and to Distinguished Professor in 2010. He has served as Director of the Center for Molecular Immunology & Infectious Disease and Co-Director of the Graduate Program in Molecular Medicine at Penn State. In 2010, he started his current position as Chair of the Department of Microbiology & Immunology in the College of Veterinary Medicine at Cornell University in Ithaca. At Cornell, he continues to work on these and other issues, including the target of the immunosuppressant BTP, an actin binding protein called drebrin.