Chlamydia infections are responsible for the bulk of sexually transmitted bacterial diseases and are the leading cause of infectious blindness (trachoma) in the world. My laboratory’s main interest is to understand how these obligate intracellular bacterial pathogens manipulate host cellular functions to replicate, disseminate and ultimately cause disease.

Chlamydia trachomatis resides within a membrane bound compartment (“inclusion”). From this location, the pathogen manipulates the actin cytoskeleton, microtubule-based motors, inhibits lysosomal recognition of the inclusion, activates signaling pathways, re-routes lipid transport, and prevents the onset of programmed cell death. Remarkably, all of these functions are achieved with a genome that encodes < 900 proteins, indicating that the Chlamydia genome is streamlined for intracellular survival.

Our laboratory focuses on identifying and characterizing the bacterial factors that are secreted across the inclusion to manipulate eukaryotic cellular functions. We use a combination of cell biological techniques, biochemistry, genetics, genomics, proteomics and molecular biology to determining the function of chlamydial virulence factors that reveal novel facets of the cell biology of host-pathogen interactions and how these factors are translocated into the host. We also have developed new methods to perform genetic analysis in these formerly genetically intractable bacteria which we have now extended to other microbes of importance in human health.

Raphael Valdivia, PhD, received his B.S. in Microbiology from Cornell University in 1991. He moved to California to begin graduate studies with Stanley Falkow in the Department of Microbiology and Immunology at Stanford University. In Dr. Falkow’s laboratory Dr. Valdivia devised a fluorescence-based screen to identify virulence factors that are induced when pathogens enter a host cell and which are involved in remodeling the host cell’s endosomal compartments.  In the process, he developed new generations of green fluorescent proteins that are widely used today.  In 1998, Dr. Valdivia received a Damon Runyon Cancer Research Fellowship and moved to the University of California, Berkeley to study endosome dynamics and biogenesis in the laboratory of Randy Schekman. At Berkeley, Dr. Valdivia used the formidable tools of genetics and biochemistry of the yeast Saccharomyces cerevisiae to uncover novel transport pathways between endosomal compartments.

Dr. Valdivia is particularly interested in developing new methods and technologies to tackle understudied microbial diseases that have been traditionally recalcitrant to experimentation.  In his current work, Dr. Valdivia focuses on the mechanisms used by the widely disseminated intracellular pathogen Chlamydia trachomatis to cause sexually transmitted infections.  His laboratory has developed and applied a range of techniques from new methods for bacterial genetic analysis to state-of-the art proteomic and genomic approaches to identify and characterize Chlamydia virulence factors.

In 2004, Dr. Valdivia earned recognition as a Pew Scholar in the Biomedical Sciences. He was also the recipient of the 2007 Merck Irving S. Sigal Award from the ASM, and he was selected as a 2007 Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases. Dr. Valdivia also serves as an editor in multiple journals (PLoS Pathogens, Pathogens and Disease, the Journal of Bacteriology, and Infection and Immunity), is a standing member of NIH review panels, and was elected Fellow of the American Association for the Advancement of Science (AAAS) in 2012. Dr. Valdivia is the founding Director of the Duke Center for the Genomics of Microbial System (GeMS).

Google Scholar Profile 

Representative Publications:

Kokes, M., Barker, J., Dunn, JD, Nguyen, BD, J, Granek, Valdivia, RH., and Bastidas, R. (2015) Integrating chemical mutagenesis and whole genome sequencing as a platform for forward and reverse genetic analysis in Chlamydia. Cell Host & Microbe (In Press)

Chen YS, Bastidas, RJ, Saka, HA, Carpenter, VK, Richards, KL, Plano GV, and Valdivia, RH (2014) The Chlamydia trachomatis Type III Secretion Chaperone Slc1 Engages Multiple Early Effectors, Including TepP, a Tyrosine-phosphorylated Protein Required for the Recruitment of CrkI-II to Nascent Inclusions and Innate Immune Signaling. PLoS Pathog DOI: 10.1371/journal.ppat.1003954

Nguyen BD, Valdivia RH. (2012) Virulence determinants in the obligate intracellular pathogen Chlamydia trachomatis revealed by forward genetic approaches. Proc Natl Acad Sci U S A. 109:1263-1268.

Saka HA, Thompson JW, Chen YS, Kumar Y, Dubois LG, Moseley MA, Valdivia RH. (2011) Quantitative proteomics reveals metabolic and pathogenic properties of Chlamydia trachomatis developmental forms. Mol Microbiol. 82:1185-1203.

Nguyen, B.D., Cunningham, D., Liang, X., Chen, X., Toone, E.J., Raetz, C.R., Zhou, P., and Valdivia, R.H. (2011) Lipooligosaccharide is required for the generation of infectious elementary bodies in Chlamydia trachomatis. Proc Natl Acad Sci U S A. 108:10284-10289.

Jorgensen, I., Bednar, M.M., Amin, V., Davis, B.K., Ting, J.P., McCafferty, D.G., and Valdivia, R.H. (2011) The Chlamydia protease CPAF regulates host and bacterial proteins to maintain pathogen vacuole integrity and promote virulence. Cell Host Microbe. 10:21-31.

Spaeth, K.E., Chen, Y.S. and Valdivia, R.H. (2009) The Chlamydia type III secretion system C-ring engages a chaperone-effector protein complex. PLoS Pathog. 5(9):e1000579. [Epub 2009 Sep 11].

Kumar, Y., and Valdivia, R.H. (2009) Leading a sheltered life: Intracellular pathogens and maintenance of vacuolar compartments. Cell Host Microbe. 5:593-601.

Kumar, Y., and Valdivia, R.H. (2008) Actin and intermediate filaments stabilize the Chlamydia trachomatis vacuole by forming dynamic structural scaffolds. Cell Host Microbe. 4:159-169.

Cocchiaro, J.L., Kumar, Y., Fischer, E.R., Hackstadt, T., and Valdivia, R.H. (2008) Cytoplasmic lipid droplets are translocated into the lumen of Chlamydia trachomatisparasitophorous vacuole. Proc Natl Acad Sci USA. 105:9379-9384.

 For a complete list of publications, click here.