Trained in molecular genetics, Dr Gibson is keenly interested in understanding the molecular mechanisms underlying complex genetic diseases, like autoimmune SLE, as a first step to identifying therapeutics for disease intervention. Dr Gibson’s original training is in the structure and function of activator genes regulating gene expression in unicellular eukaryotes, but he has since focused on structural genetic and epigenetic mechanisms driving autoimmune SLE. Using cutting-edge biochemical and genetic tools in model cellular systems and in human primary cells, Dr Gibson works on identifying and characterizing SLE-linked genetic variants that confer disease risk or severity, including genes encoded at the chromosome 1q21-q23 locus. In this effort, he has examined the genetic structure and expression of FcRL3 variants and their role in SLE, and the structure and function of FcgammaRI-FcRg, the high-affinity IgG receptor complex that mediates ADCP and clearance of immune complexes in phagocytes. His work on the alpha-chain of FcgRI, which binds IgG and IgG-immune complexes, has revealed contributions of the cytoplasmic domain to receptor signal transduction, and his work on the structure/function of gamma chain, the signaling molecule in the receptor complex, has identified specific residues (beyond the traditional ITAM tyrosine phosphorylation) that regulate function as well as intracellular molecular players that modify these residues. Dr Gibson’s more recent work has focused on the characterization of novel structural genomic variation at 1q23 which may alter the balance of activation vs inhibitory Fc receptor gene expression and alter downstream functions like ADCP that impact SLE disease. Ultimately, Dr Gibson’s work will identify novel molecular targets for improved ADCP and vaccine efficacy, and for therapeutic intervention in management of immunologic diseases.
