- B.S., Univeristy of California at Irvine, 1986
- Ph.D., Washington State University, 1992
- Postdoc., University of California-Los Angeles, 1992-96
My laboratory studies Borrelia burgdorferi, the spirochetal bacterium that causes Lyme disease. B. burgdorferi
is the most common arthropod-borne infectious agent in the United
States, with over 27,444 cases reported to the CDC in 2007. This number
represented a significant increase from the previous years, indicating
that B. burgdorferi is a re-emerging infectious agent.
The goals of my research are to understand how B. burgdorferi causes disease and adapts to different niches it occupies by: (1) addressing the role of attachment, colonization and subsequent dissemination using newly developed genetic methodologies to inactivate genes involved in adherence of B. burgdorferi to host tissues; and (2) understanding how B. burgdorferi responds to oxidative stress via the function of the global regulatory protein BosR.
In regard to the first project, and in collaboration with Magnus Höök’s group, we are studying how binding by B. burgdorferi to host structures impacts the infectious process. Our initial studies evaluated the role of the fibronectin binding protein of B. burgdorferi (BBK32) in borrelial pathogenesis. This work suggested that BBK32 is required for full virulence in the mouse animal model system of Lyme borreliosis. Subsequent studies have focused on the borrelial decorin binding protein adhesins, DbpBA. When the dbpBA genes are deleted from B. burgdorferi, the spirochetes are significantly attenuated in the mouse model of infection, indicating that the Dbp proteins are essential for maximum virulence of B. burgdorferi. We are currently addressing how additional B. burgdorferi proteins affect colonization, dissemination, and persistence, as well as how they alter the host immune response, to further elucidate the importance of these borrelial proteins in Lyme pathogenesis.
For the second project, the role of the BosR redox regulator is being addressed. The BosR protein is a homologue to the PerR regulator, a protein whose activity in other bacterial systems is associated with a response to oxidative stressors. Using both biochemical and genomic based approaches, we have identified several genes, including the lone superoxide dismutase encoded by B. burgdorferi, that are putatively involved in the oxidative stress response and regulated by BosR. We contend that B. burgdorferi responds to the redox status of its locale and uses this, in addition to pH and temperature, as a cue to modulate gene expression in order to adapt to its environment via BosR as well as other regulatory pathways. We have recently discovered that gas content (O2 and CO2) also dramatically modifies gene expression in B. burgdorferi and are in the process of further determining how this response overlaps with BosR function.
Current Genetics Students: