Technological achievements in antibody engineering have made antibody drug development one of the fastest growing areas of the pharmaceutical industry. Successful design of antibody based therapeutics or diagnostics requires both the ability to optimize the antibody and a clear understanding of the biology of the target antigen. To this end, our laboratory has two main focuses: 1) To identify and build a functional understanding of novel molecular targets, often utilizing custom antibodies as powerful tools to expedite the research and 2) to develop high throughput strategies and engineering methods to modify the affinity, specificity, epitope site recognition and Fc function of antibodies for therapeutic, diagnostic, and basic research use. Utilizing molecular imaging techniques, antibody agent development can be monitored using in vivo models to predict efficacy, specificity and for target validation prior to the clinic. This line of research allows our laboratory to venture into a number of diverse biological fields, with ongoing projects currently focused in oncology and infectious disease.
Peng Gao, Ph.D
My research focus on two projects: “Regulation of Enterococcus faecalis surface protein expression” and “The role of E. faecalis RNase J2 (rnjB) in gene expression and bacteria virulence”. Using high-affinity antibodies against specific enterococcal antigens, we have successfully established a whole-cell ELISA based transposon library screen method to identify genetic elements that affect surface protein expression. We further demonstrated that these genes, by regulating surface protein expression, affect functional processes including biofilm formation and cell attachment. We also use microarray analysis to compare transcriptomes of the wild-type E. faecalis and the isogenic rnjB deletion mutant to investigate the functional role of E. faecalis RNase J2. A sub-lethal IV challenge mouse model demonstrated that deletion of RNase J2 greatly attenuate bacterial virulence.
Research Associate II
In addition to general lab management duties, my research focuses on the generation and development of monoclonal antibodies for research, diagnostic imaging and potential therapeutic applications. Our lab has generated panels of high affinity antibodies through hybridoma technologies against many virulence factors present on the surface of enterococci including pili and the collagen binding domain, Ace. Our recent publication, “Targeting pili in enterococcal pathogenesis” emphasizes how we can apply our efforts to translational medicine. Additionally, directed panels of antibodies act as tools to improve our understanding of gene regulation and post transcriptional modification of surface protein expression in enterococci.
I received a B.A. in Zoology and French from Ohio Wesleyan University. The focus of my current work is on understanding the regulation of surface proteins of the bacterium Enterococcus faecalis, many of which have been associated with enterococcal pathogenesis. In particular, we are interested in post translational modifications to surface proteins caused by a secreted metalloprotease, GelE. Through published and ongoing work, our lab has demonstrated that GelE cleavage is important in regulating the activity of a sub-class of surface proteins, impacting cell adhesion, division and biofilm formation. By understanding the underlying mechanisms of surface protein regulation, we are better able to devise strategies to prevent E. faecalis infection.