I. Allergies and the Immune System
II. A Role for the Actin-Reorganizing Protein Drebrin in Mast Cell Function
Part I: Allergies and the Immune System
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In his first talk, August gives an overview of how cells of the immune system interact to generate an allergic response. When epithelial cells are exposed to an allergen, a cascade of signaling events causes B cells to begin producing IgE. Circulating IgE binds to receptors on the surface of mast cells or basophils. Upon subsequent exposure, the allergen will bind to IgE and trigger the release of the contents of granules found in mast cells and basophils. These granules contain histamine, heparin, proteases, cytokines and other signaling molecules that are responsible for causing the many symptoms of allergies. August explains how drugs that prevent degranulation or counteract the actions of granule contents (such as anti-histamines) can help prevent an allergic response.
In his second lecture, August describes research into the molecular basis of mast cell degranulation. The binding of IgE to the Fc receptor on mast cells causes an increase in intracellular Ca2+ that is important for both cytokine production and degranulation. Experiments in August’s lab identified the actin binding protein Drebrin as the target of an immunosuppressant that can block mast cell degranulation. His lab generated Drebrin knockout mice and compared the response of mast cells from the knockout and wild type mice to Fc Receptor activation. They showed that the absence of Drebrin blocked Ca2+ influx upon receptor activation and blocked both degranulation and cytokine production. Further experiments investigated where Drebrin fits into the signaling pathways downstream of the Fc receptor.
When Avery August was a teenager, he moved with his family from Belize to Los Angeles. Unhappy with high school in Los Angeles, August quit and instead completed his GED. He spent two years at community college before transferring to California State University in Los Angeles. Supportive mentors at CSU gave August a chance to do research, an experience that prompted his decision to attend graduate school. August received his PhD in immunology from Weill Cornell Graduate School of Medical Sciences in New York City, and he was a post-doctoral fellow with Hidesaburo Hanafusa at Rockefeller University.
August spent two years working at the pharmaceutical company Johnson and Johnson before returning to academia at Pennsylvania State University from 1999-2010. In 2010, August moved to Cornell University, in Ithaca NY, to become Chair of the Department of Microbiology and Immunology in the College of Veterinary Medicine. His lab investigates the role of tyrosine kinases, specifically the Tec kinases, in regulating the immune system.
As well as directing outstanding research, August is actively involved in mentoring and encouraging underrepresented minority students and trainees to pursue careers in science. August received the E.E. Just Award from the American Society of Cell Biology in 2014.
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Law M, Lee Y, Morales JL, Ning G, Huang W, Pabon J, Kannan AK, Jeong AR, Wood A, Carter C, Mohinta S, Song J, August A. (2015) Cutting Edge: Drebrin-Regulated Actin Dynamics Regulate IgE-Dependent Mast Cell Activation and Allergic Responses. J Immunol. Jul 15;195(2):426-30.
Oettgen HC, Burton OT. (2015) IgE receptor signaling in food allergy pathogenesis. Curr Opin Immunol. Oct;36:109-14.