“Ten to 20 percent of the population of industrialized countries suffers from some form of allergies. There is a huge need to understand this disease and to find therapeutic interventions.” – Toshiaki Kawakami, M.D., Ph.D.
Dr. Kawakami has been with LIAI since 1988, joining originally as an
Assistant and then Associate Member in the Biochemistry Section of the
Division of Immunobiology. Dr. Kawakami then became an Associate Member
in the Allergy Division in 1996 and in 2000 he became a full Member. He
is also an Adjunct Professor at the University of California, San
Diego's Department of Medicine. Dr. Kawakami's research at LIAI focuses
on signal transduction, especially in mast cells, which trigger
allergic reactions.
Dr. Kawakami received his M.D. from the University of Tokyo in 1978 and
his Ph.D. in 1983 in the field of Molecular Biology. While working
towards his Ph.D., Dr. Kawakami acted as an Assistant Professor in the
department of Physiological Chemistry and Nutrition at the University
of Tokyo but in 1984 he began work as a visiting fellow at the National
Cancer Institute in Bethesda, Maryland. In 1987, Dr. Kawakami spent a
year in the Cell Development and Oncology lab at the National Institute
of Dental Research, also in Bethesda, before returning to Kyoto in 1988
where he spent two years as an Assistant Professor in the Department of
Medical Chemistry, Kyoto University, Faculty of Medicine.
Dr. Kawakami received the Fogarty International Fellowship in 1984 and
is currently an Associate Editor for the Journal of Immunology, and a
reviewer for numerous publications. He gave three plenary lectures in 1998 at the First Annual Meeting of Surface Barrier Research against Infection, The Third Annual Meeting on New Topics of Clinical Immunology and Allergy and at The Thirty Fifth Annual Meeting of the Japanese Society of Pediatric Allergy. In 2004 he was inducted as a Member of the Collegium Internationale Allergologicum.
Toshiaki Kawakami, M.D., Ph.D., and his team study signal transduction
in the immune and hematopoietic systems. The laboratory has been
studying mainly mast cells, an important cell type found in mucosal as
well as connective tissues that is responsible for the allergic
reactions that trigger itching, wheezing, and sneezing. These symptoms
of allergic reactions occur after mast cells are activated.
When exposed to allergens (substances, such as pollen, that cause
allergies), IgE-bound mast cells are activated and secrete numerous
chemical, lipid, nucleotide, peptide, and protein mediators. These
mediators, together with other immune cells, are believed to
orchestrate complex cellular and molecular interactions to induce
allergic reactions. Increasing numbers of signaling molecules are shown
to be important for mast cell activation. Dr. Kawakami and his
colleagues focus on dissecting the complex network of signaling
molecules, particularly those involved in the early phase of mast cell
activation.
Conventional belief was that IgE-mediated mast cell activation
requires multivalent allergen or antigen to induce mast cell
activation. However, in 2001 Dr. Kawakami and his colleagues found that
IgE can induce mast activation without the involvement of allergen or
antigen. They later showed a vast heterogeneity in IgE molecules in
their ability to induce this IgE effect (so-called "monomeric IgE
effect"): some IgEs can induce all kinds of activation events, but
others can do so very inefficiently. Currently, they are trying to
understand how these fundamental observations can be translated in
allergic diseases.
Principles of signaling mechanisms in mast cells are shared not only
by other immune and hematopoietic cells but also more distantly related
cells. Abnormalities in signaling networks can lead to many types of
disorders including cancer, autoimmune diseases, and
immunodeficiencies. Microbes often hijack such intricate networks for
their advantage. Therefore, Dr. Kawakami's team sometimes ends up
studying cancer and virus infection, even when their original interest
is in allergy research. An interesting extension of their study is an
establishment of a mouse model of atopic dermatitis and a subsequent
use of that model to study eczema vaccinatum. Eczema vaccinatum is a
serious infection with vaccinia virus often experienced when patients
with atopic dermatitis are vaccinated against smallpox. Another
exciting finding is a recent identification of a novel tumor suppressor
that was originally supposed to play an important role in mast cell
activation. They hope their study of signaling molecules may lead to an
increased understanding of these diseases and contribute to new
preventive measures, diagnostics, and treatments.
Pivotal advance: IgE accelerates in vitro development of mast cells and modifies their phenotype. J Leukoc Biol. 2008
Regulation of myeloproliferation and M2 macrophage programming in mice by Lyn/Hck, SHIP, and Stat5. J Clin Invest. 2008
Human IgE+ and IgE- are not equivalent to mouse highly cytokinergic IgE. J Allergy Clin Immunol. 2008
Basophils now enhance memory. Nat Immunol. 2008
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