Research in the Donald MacGlashan Laboratory aims to understand the regulation of secretion from human basophils and mast cells—two cells thought to play key roles in allergic reactions and other diseases. The hallmark reaction in these cells is degranulation through cell-bound IgE. Our interests lie in the signaling mechanisms that control this dramatic cell response and the factors that regulate the degree of the reaction.

Dr. Dispenza’s laboratory focuses on allergies and IgE-mediated allergic reactions including anaphylaxis.  Overall goals of the lab include understanding the mechanisms driving anaphylaxis severity and phenotypes, discovering new biomarkers for the accurate diagnosis of anaphylaxis, and developing novel strategies for the prevention of IgE-mediated reactions.  One major project focuses on the prevention of anaphylaxis, for which there are no known reliable preventative therapies.  They found that small molecule inhibitors of the enzyme Bruton’s tyrosine kinase (BTK), which is a key component of the IgE signaling pathway, completely suppress IgE-mediated human mast cell and basophil activation and significantly protect against death from severe anaphylaxis in humanized mice.  Further, in an investigator-initiated clinical trial, they demonstrated in an investigator-initiated trial that treatment with just 2 days of the oral BTK inhibitor acalabrutinib completely prevents clinical reactivity from eating peanut in the majority of peanut-allergic adults and markedly increases the tolerance level of the remainder.  These exciting data suggest that a long sought-after preventative therapy for anaphylaxis may finally be within reach.

The John Schroeder Lab focuses on understanding the role human basophils and mast cells play in allergic reactions, as it relates not only to their secretion of potent inflammatory mediators (e.g., histamine and leukotriene C4) but also to their production of pro-inflammatory cytokines. We have long utilized human cells rather than cell lines in order to address the parameters, signal transduction and pharmacological aspects underlying clinically relevant basophil and mast cell responses. As a result, the lab has established protocols for rapidly isolating large numbers of basophils at high purity from human blood and for growing culture-derived mast cells/basophils from human progenitor cells. A variety of assays and techniques are also in place for concurrently detecting cytokines and mediators following a wide range of stimuli. These have facilitated the in vitro testing of numerous anti-allergic drugs for inhibitory activity on basophil and mast cell activation. The lab also studies counter-regulation between the IgE and innate immune receptors on human immature dendritic cell subtypes.

The research in the Sarbjit Saini Laboratory focuses on IgE receptor biology and IgE receptor-mediated activation of blood basophils and mast cells. We have examined the role of IgE receptor expression and activation in allergic airways disease, anaphylaxis and chronic urticaria. Our research has been supported by the NIH, American Lung Association and the AAAAI. Our current research interests have focused mechanisms of diease in allergic asthma, allergic rhinitis and also translational studies in chronic idiopathic urticaria.