Jun (Jay) Zhu, Ph.D.

Assistant Professor of Microbiology

Office Address:
University of Pennsylvania School of Medicine
201B Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104-6076

TEL 215-573-4104
LAB 215-573-4105
FAX 215-898-9557
junzhu@mail.med.upenn.edu

Click here for the Zhu Lab Site

RESEARCH SUMMARY

My laboratory is interested in studying quorum sensing in related to bacterial pathogenesis in Vibrio cholerae, which causes a severe watery diarrhea cholera disease, and other intestinal human pathogens. V. cholerae colonizes the small intestine and produces a range of virulence factors, including cholera toxin. Cholera is still endemic in many parts of developing countries, where seasonal outbreaks occur widely. Quorum-sensing refers the ability of a microorganism to perceive and respond to microbial population density, usually relying on the production and subsequent response to diffusible signal molecules. More recently, the role of quorum sensing in virulence regulation has been noted in several clinically important bacterial pathogens, including V. cholerae, and quorum sensing pathways may therefore be a useful target for novel antimicrobial therapies.

Recent in vitro studies reveal that quorum sensing systems control V. cholerae virulence gene expression and biofilm formation. To demonstrate the significance of the relationships among quorum sensing, pathogenesis and biofilm development in V. cholerae, we study the in vivo role that quorum sensing plays during V. cholerae infection. We are modifying the current RIVET (Recombinase-mediated in vivo expression technology) system to examine both induction and repression of gene expression during infection. We use various tools (such as genetic analysis, whole-genome microarry analysis) to investigate correlations between V. cholerae quorum signal accumulation and virulence gene expression in vivo. We will apply chemical genetics to set up high throughput screens of chemical libraries to identify organic molecules that mimic the activity of quorum sensing molecules. These small molecules could represent a potential novel drug for treating cholera patients.

We are also interested in V. cholerae biofilm formation and its roles in V. cholerae infectious cycles. We have identified a compound present in the mouse intestinal lumen significantly stimulates V. cholerae biofim formation. We take a biochemical approach to study the nature of these biofilm stimulators. We will identify the corresponding bacterial receptors by using microarrays, genetic screening, and affinity pull-down experiments. We also study the various forms of V. cholerae present in cholera patients’ stools and determine whether biofilm formation is responsible for the hyperinfectious state of V. cholerae isolated from patients.

Our interest in quorum sensing extends beyond single-species cell-cell signaling, and here too we intend to conduct our research within the context of microbe-host interactions. We have already initiated studies on cell-cell communication among the normal flora of the human intestine, beginning with enterobacteria that cause nosocomial infections. In the intestine, a relatively harmonious balance among the normal flora is maintained, however, this balance may be easily perturbed by the introduction of a single pathogen or an antibiotic. We will obtain transcriptional profiles in response to secreted signal molecules from other species, by microarray analysis, or by transposon mutagenesis. We are not intending to limit ourselves to study known quorum signals, but rather any interspecies signals that have the capacity to turn on/off pathogenesis-related pathways. We have established novel polymicrobe-host model systems to examine the combinations of bacterial strains that change invasive patterns. We believe that these novel approaches to study interspecies communication may allow us to explore the mechanisms by which the diverse intestinal population normally maintains its balance and the means by which it reacts to external perturbation.

SELECTED RECENT PUBLICATIONS

Liu, Z., T. Miyashiro, A. Tsou, A. Hsiao., M. Goulian, and J. Zhu. 2008. Mucosal Penetration Primes Vibrio cholerae for Host Colonization by Repressing Quorum Sensing. Proc Natl Acad Sci U S A. 105:9769-9774.

Hsiao, A, K. Toscano, and J. Zhu. 2008. Post-transcriptional cross-talk between pro- and anti-colonization pili biosynthesis systems in V. cholerae. Mol. Microbiol. 67: 849ö860.

Liu, Z., Stirling, F. and J. Zhu. 2007. Temporal quorum sensing induction regulates Vibrio cholerae biofilm architectures. Infect. Immunity. 75: 122-126.

Hsiao, A., Z. Liu, A. Joelsson, and J. Zhu. 2006. Vibrio cholerae virulence regulator-coordinated evasion of host immunity. Proc. Natl. Acad. Sci. USA. 103:14542-14547.