Currently, there are four major areas of research (along with a host of smaller developing projects). It is worth noting that the vast majority of what we do focuses on the behavior of the wild-type basophil or mast cell rather than employing a variety of cell line or animal cell models. This does not mean that we exclude studies using other types of cells but have chosen to devote precious resources to determining important characteristics of these very difficult to study cells. It should go without saying that there are a wide variety of collaborative efforts, many with members of this division.
As part of a long-standing funded NIH grant, we remain deeply involved in working out the mechanisms that down-regulate an ongoing IgE-mediated reaction in these cells. This process of down-regulation is probably related to a process that has been termed desensitization. The basic observation is that ongoing secretion is stopped before reaching maximal levels (as defined by other means). A variety of past efforts have begun to narrow down the candidate points in the signaling cascade that are affected by the desensitization process. As of yet, there are no clear cut candidate molecules that cause desensitization in human cells. Recent studies indicate that two forms of desensitization (specific and nonspecific) operate before or after, respectively, the activation of the receptor-associated kinase, syk. Current efforts seek to begin probing events preceding syk activation as well as events that lie between syk activation and the mobilization of cytosolic calcium (which is shut off in desensitized cells). A more recently funded enterprise relates to the observation that IgE antibody controls the expression of the high affinity receptor for IgE on basophils and mast cells. There are some practical implications for this piece of cell biology, in particular how it relates to the success of the new anti-IgE antibody therapy for allergies, so we are examining several aspects of the process. As usual, we are interested in the mechanism underlying the control of receptor expression by IgE.