Mariana Castells, MD, PhD

Professor of Medicine, HMS

Mast Cell Inhibitory Mechanisms

Mast cell degranulation leads to anaphylaxis and cardiovascular collapse can occur within minutes, but the mechanisms but which it can be inhibited are poorly understood. My research laboratory is aimed at mast cell inhibitory mechanisms. Based on mast cell inhibitory capacities my lab has generated a model of rapid IgE desensitization that leads to temporary uncoupling of signal transduction and unresponsiveness to antigen. Against established dogma, desensitization is an active and specific process that stabilizes antigen, IgE and FcεRI at the cell surface preventing internalization and extracellular calcium influx. Current research includes the use of humanized mouse mast cell transgenes to assess desensitization through the human IgE receptor FcεRI and the use of basophil tests to assess in vitro and in vivo activation and desensitization to chemotherapy, antibiotics, and monoclonal antibodies in allergic patients.