Peter F. Weller, MD
The Cellular and Molecular Bases of Inflammation - This laboratory, directed by Dr. Peter Weller , has many active areas of basic laboratory research centered around understanding basic mechanisms of leukocyte functioning in forms of inflammation. The two principal areas of investigation are: 1) the immunobiology of eosinophilic leukocytes and 2) the intracellular regulation and compartmentalization of inducible mediators of inflammation in neutrophils and other leukocytes.
Studies of human eosinophils are aimed at defining mechanisms whereby eosinophils may collaboratively interact with other cellular elements of the immune system. These studies include investigations of the mechanisms whereby eosinophils may function as antigen-presenting cells in governing T-lymphocyte dependent immune responses, and include investigations of the in vivo migration and function of eosinophils and of the regulated expression of cell surface proteins involved in collaborative interactions between eosinophils and other cell types. Additional studies are focused on defining the molecular mechanisms governing the synthesis, granule storage and release mechanisms of eosinophil derived cytokines. The roles of eosinophils in wound healing and fibrosis and the activities of chemokines and cytokines released by eosinophils that contribute to tissue remodeling are being studied. The second area of research involves the molecular and cellular biologic bases of inducible responses of leukocytes participating in host defense and other forms of inflammation. These are centered on a unique intracellular compartment, termed the lipid body, whose formation is rapidly inducible in leukocytes. The intracellular signaling mechanisms responsible for lipid body induction and especially the roles of lipid bodies as distinct sites of cytokine and eicosanoid mediator formation are being studied. In addition to investigating previously undefined pathways of leukocyte responses to inflammation, these studies also offer the potential to identify novel anti-inflammatory therapeutic targets. Our research indicates that lipid bodies in leukocytes have roles as sites of regulated formation of eicosanoids and as distinct extranuclear sites of transcription and translation. The biology of these structures is intimately related to the roles of leukocytes in acute inflammation.