The mast cell is the cornerstone of allergic disease, what we commonly refer to simply as allergies. Allergic disease has a very broad range of types and a broader range of allergic triggers. More than 30% of Americans are subject to some form of allergic disease, and several thousand of asthmatics die every year as a result of their allergic reaction. All allergic diseases are manifested by an immune system over-reaction to a substance that the body should not normally identify as dangerous, and that reaction can be something as basic as a mild irritation or it can be so extreme as to cause fatal results.
Because allergic disease has such a variety of causes and effects on individuals, understanding the biology of the functions behind it is vitally important, and this is the work that Toshi Kawakami, M.D., Ph.D. and his lab are undertaking.
The Kawakami lab has been studying the roles of several tyrosine kinases (an enzyme that modifies proteins) and the signaling proteins they interact with in the early process of mast cell activation. When a mast cell is “activated” it releases chemicals into the body that cause what we know as an allergic reaction. In the course of following these kinases and signaling molecules, the lab discovered some intriguing behaviors. Their recent findings have been able to link the same kinases and other signaling molecules that activate mast cells in allergic disease to cancer. Systems that are lacking in these substances are more prone to develop cancerous blood tumors.
Understanding the detailed mechanisms of a disease is essential for developing novel therapeutic strategies, and this understanding is greatly helped by developing and characterizing an animal disease model. The Kawakami lab recently developed a novel model of atopic dermatitis, an allergic skin disease. Their work in examining this model has led them to another interesting new area. Individuals who have the relatively benign allergy atopic dermatitis are excluded from smallpox vaccination due to the danger of possible serious side effects, including eczema vaccinatum. They are now extending this mouse model to study the mechanism of eczema vaccinatum, and how these allergic signaling molecules are affected by the smallpox vaccinia virus.
The Kawakami lab is now in the process of further exploring just how the factors that can activate mast cells and allergic reactions are involved in other processes in the immune system. With work that has already touched upon allergic disease, infectious disease and cancer, the lab is keeping their eyes open for more far-reaching effects for their research.