Moczygemba Lab

The research focus of the Moczygemba laboratory is to develop interventional strategies that block allergic inflammation through our increased understanding of cytokine signaling and eosinophil biology.  The eosinophil and its major activator, IL-5, play an important role in the pathogenesis of allergies and asthma.  Thus, one of our goals is to understand regulatory mechanisms that control the intensity and duration of IL-5-mediated eosinophilic signaling.  To this end, we employ various cellular, immunological, and biochemical techniques to help us identify novel targets capable of modulating inflammatory signals triggered by eosinophils.

One area of deep interest in our lab is the molecular characterization of IL-5 receptor ubiquitination especially that associated with the common beta chain (betaC).  Previously we demonstrated that the betaC cytoplasmic tail was ubiquitinated and degraded by proteasomes after IL-5 stimulation.  We have since identified a cluster of three membrane-proximal lysine residues (K457, K461, and K467) on betaC that are required for JAK1 and JAK2 binding, and betaC ubiquitination.  Importantly, we found that in the absence of these three lysine residues, bc ubiquitination, endocytosis and signaling were significantly impaired, indicating that JAK binding to bc is an essential step in IL-5 receptor regulation.

In a related project associated with allergic inflammation, we are collaborating with our colleagues from MD Anderson Cancer Center in Houston.  The major focus of this project is to harness the activation of lung innate immunity using aerosolized TLR Ligands to modulate the asthmatic immune response.  Recent findings indicate that administration of aerosolized antigen with a specific combination of TLR ligands has a major effect on the immunomodulation of the allergic IgE response and eosinophilic inflammation in a murine model of experimental asthma.  Insight into these immunomodulatory mechanisms could potentially identify novel targets for controlling inflammation associated with asthma.