The lab focuses on the two key paradigms inthe combinatorial library approach, namely, the combination / recombination vs.elimination / selection of a natural repertoire using the principle ofevolution.  In particular, our currentresearch direction is to design and establish suitable phenotypic screeningmethods in cells and insects (animals) to identify novel antibodies withspecific functions and biological activities from the available high diversity(1x10E11) antibody combinatorial library. Our main research interest is in thefields of tumor immunology, metabolic diseases, and rare genetic diseases,associated with gap junction channels mutation.

To identify a novel antibody withbiological function, we rely on robust and effective screening methods. Tofully utilize the power of the first generation phage display and the secondgeneration intra-cellular combinatorial antibody library technologies, the labhas established a series of cellular assays based on function, morphology, andcell signaling pathways, for example the beta-lactamase reporter gene assay,the primary cell proliferation assay, the cancer cell proliferation sortingassay, and the myocardial cell toxicity assay. Living body is a complicatedsystem and represents the next frontier for the combinatorial librarytechnology. We are configuring a study model in c. elegans for the in vivocombinatorial antibody library approach. In addition, we are developing relevant murine models for the study ofhepatocyte expansion and regeneration.

Alongside with the screening methods, wewant to develop a series of informatics tools that can reproduce theexperimental results, and eventually predict them. A combination of homologymodeling, docking prediction and molecular dynamics simulation will be used tounderstand how antibodies and selected proteins interact. The aim is to providean explanation of experimental results at the molecular level and eventuallyuse rational design for select the correct antibody a priori. In order to set up and test the methodology, we willfirst analyze the effect of binding of antibodies to gap junction channels and tothe acid sensic channels, aiming at finding specific blockers for thesechannels or to modify their permeation properties.