Host-bacterial interactions

Our research interests in the host-bacterial interaction theme lie in the application of systems biology approaches to the study of pathogenesis of infectious diseases. More generally, I am interested in understanding how complex signaling pathways control the flow of cellular information as an integrated system. The overall goal of the following proposed research is to identify signaling components in both host immunity and bacterial pathogenesis pathways and to establish a framework for placing these diverse components into an integrated network, and then to use the knowledge from these studies to develop novel strategies to defend against pathogen attack. My lab is one of only a handful in the world that focuses on defense responses of both plants and animals against Pseudomonas aeruginosa, an opportunistic bacterial pathogen with extremely broad host range. In addition, we also study other bacterial pathogens of global significance, including intracellular pathogen, such as Shigella.

Pseudomonas antibiotic persistence

Pseudomonas aeruginosa is a Gram-negative opportunistic bacterial pathogen that causes life-threatening infections in cystic fibrosis (CF) patients and immuno-compromised individuals. Pseudomonas aeruginosa is one of the most common causes for nosocomial infections with high morbidity and mortality rates. No vaccines are available for this bacterium, and treatment is difficult due to multidrug resistance. Pseudomonas aeruginosa forms biofilms in the infected lungs, making eradication of its infections challenging. Another major obstacle for treatment of P. aeruginosa infection is the formation of bacterial persister cells, phenotypic variants that are not genetically resistant to antibiotics but tolerant to high concentrations of antibiotics. Persistence in the presence of antibiotics is a transient phenotype that is developed as a consequence of heterogeneous responses to the environment within a genetically identical bacterial population. Our lab aim to facilitate both basic understanding of P. aeruginosa persisters as well as practical applications in the prevention and eradication of persister-mediated infections.

RACKology

Receptor for Activated C Kinase 1 (RACK1) is a highly conserved, multifunctional scaffolding protein that coordinates a variety of fundamental cellular processes in all eukaryotes, including signal transduction, protein synthesis and cell migration. Therefore, it is not surprising that a wide range of pathological scenarios, including developmental disorders, infectious disease, and cancer have been shown to be associated with either an increase or decrease in RACK1 protein level in the disease states. Our lab is interested in characterizing the role of RACK1 in mediating various cellular stress responses, thereby contributing to disease mechanisms, including various cancers.