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Avery August, PhD
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Avery August, PhD

  • Professor of Immunology
101 Henning Building
University Park, PA 16802
Email: axa45@psu.edu
Phone: (814) 863-3539

Education:

  1. Postdoctoral training, Laboratory of Molecular Oncology, The Rockefeller University, New York (with Dr. Hidesaburo Hanafusa)
  2. Ph.D., Immunology, Cornell University (with Dr. Bo Dupont)
  3. B.S., Medical Technology, California State University , Los Angeles

Biography:

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 nonreceptor TKs.


Regulation of T cell activation and function by Tec family kinases.


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. Mice lacking Itk have T-cell defects, including reduced intracellular calcium increases during T cell activation and defective Th2 development. Understanding the specific downstream activities of these kinases is crucial to understanding how they impact lymphoid activation and development.

We have recently shown that the SH3 domain functionally interacts with the Proline Rich region of ITK, regulating both basal and activation induced kinase activity. We have also recently shown that mice lacking ITK a resistant to developing immunological symptoms of allergic asthma, a disease primarily driven by Th2 type T cells. Finally, we have recently shown that Tec kinases regulate the activation of the transcription factor Serum Response Factor (SRF), and that calcium mediated pathways differentially regulate the activation of SRF and the transcription factor NFAT, such that SRF has a lower requirement for calcium, while NFAT is absolutely dependent on calcium increase, regulated by Tec kinases. 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 recent data suggest 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 recently shown that in the absence of Itk, a population of CD8 + T cells that have a memory phenotype (CD8 + CD44 + CD122 hi ) predominates. Our analysis of these cells indicate that they develop in the absence of direct signaling by Itk since they are present in transgenic mice carrying a mutant Itk with no kinase domain. We also showed that these cells have intrinsic innate immune function as the carry preformed message for the cytokine IFN gamma , and can this cytokine in response to IL-12/IL-18 stimulation. Our data suggest that these cells allow Itk null mice to effectively respond to infection with L. monocytogenes or exposure to LPS by secretion of IFN gamma . Confirming this, our experiments show that transfer of these cells rescues IFN gamma null mice during Listeria infection. We are continuing to study the function and behavior of this population of memory T cells with innate function.

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 recent experiments have started to examine the role of Itk 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 asthma 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 have recently shown that eosinophils are required for T cells to enter the lung during the development of allergic asthma.  We are continuing our analysis of the role of eosinophils in the development of allergic asthma.

Lab Members

  • Avery August - Center for Molecular Immunology & Infectious Disease & Dept. of Veterinary & Biomedical Sciences
  • Chavez Carter – Pathobiology Graduate Student
  • Ayesha Fraser - Undergraduate Student
  • Margaret Kensinger - Research Technician
  • Man Kit Law - Immunology & Infectious Disease Graduate Student
  • Sonia Mohinta - Pathobiology Graduate Student
  • Luis Morales - Post-Doc
  • Meg Potter - Research Technician
  • Patrick Power - Schreyers Scholar, Undergraduate Student
  • Qian Qi - Post-Doctoral Fellow
  • Kindra Stokes - Pathobiology Graduate Student
  • Weishan Huang - Cell & Developmental Biology Graduate Student
  • Arun Kumar - Immunology & Infectious Disease Graduate Student
  • Lina Khong - Schreyers Scholar, Undergraduate Student
  • Allison Neely - Schreyers Scholar, Undergraduate Student
  • Tammy Terosky - Research Technician
  • Adam Winters - Undergraduate Student
  • Elizabeth Fernandez - Undergraduate Student

 

Lab Alumni