Raphael Valdivia
Overview:
My laboratory is interested in how microbes influence human health, both in the context of host-pathogen and host-commensal interactions. For many pathogens, and certainly for most commensal microbes, it is is poorly understood what is the molecular basis for how host and microbial factors contribute to a beneficial outcome for us. We currently focus on two experimental systems:
Chlamydia trachomatis infections are responsible for the bulk of sexually transmitted bacterial diseases and are the leading cause of infectious blindness (trachoma) in the world. Chlamydia resides within a membrane bound compartment (“inclusion”). From this location, the pathogen manipulates the cytoskeleton, inhibits lysosomal recognition of the inclusion, activates signaling pathways, re-routes lipid transport, and prevents the onset of programmed cell death. Our laboratory focuses on identifying and characterizing the bacterial factors that are secreted into the host cell cytoplasm to manipulate eukaryotic cellular functions. We use a combination of cell biological techniques, biochemistry, genetics, genomics, live cell microscopy, proteomics and molecular biology to determining the function of virulence factors that reveal novel facets of the cell biology of host-pathogen interactions. Our ultimate goal is to understand how these obligate intracellular bacterial pathogens manipulate host cellular functions to replicate, disseminate and cause disease.
A second area of focus in my research group is the development of new methods to perform genetic analysis in many of the microbes that reside in our gut. Understanding how the collection of genetic information of microbes associated with our bodies (microbiomes) impact our health is one of the new frontiers in microbiology. We are currently studying how one specific bacterium, Akkermansia muciniphila, proliferates in the mucus layers of our lower gastrointestinal tract and contribute to nutrient homeostasis and human immunological health.
Positions:
Nanaline H. Duke Distinguished Professor of Molecular Genetics and Microbiology
Professor in Integrative Immunobiology
Chair, Department of Immunology
Professor of Cell Biology
Member of the Duke Cancer Institute
Education:
Ph.D. 1998
Postdoctoral Fellow
Postdoctoral Fellow
Grants:
IsoCyte Laser Scanning Plate Cytometer for High-throughput, High-content Assays
Live cell widefield fluorescence microscope with activation and bleaching lasers
Interferon-driven ubiquitin response targets Chlamydia inclusions in human cells
Enzymology of Chlamydial Pathogenesis
Integrated instrument systems for maintenance and delivery of RNAi libraries
Publications:
The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction.
Chlamydia repurposes the actin-binding protein EPS8 to disassemble epithelial tight junctions and promote infection.
Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment.
