Our research program focuses upon the invasive capacity of spirochete pathogens, with the goal of better understanding the mechanisms underlying pathogenesis and systemic dissemination within the host. Using a combination of molecular, cell biology, imaging, and proteomic techniques our aim is to identify and characterize adhesins and other virulence factors from the spirochetes Treponema pallidum (causative agent of syphilis) and Leptospira species (causative agent of leptospirosis).
By working with purified recombinant treponemal proteins, model treponemes, heterologous expression systems in model spirochetes, and live T. pallidum we are able to use a combinatorial approach to study this unculturable organism. We have identified a number of T. pallidum adhesins involved in attachment to host extracellular matrix components and host cell receptors, which also play a role in host immune evasion. Our current focus is to use bioinformatics in combination with proteomic, imaging, structural and cell biology techniques to (i) identify treponemal pathways for localization of T. pallidum adhesins to the host cell environment, (ii) explore adhesin interactions with human cells, including vascular and brain endothelial cells, platelets and epithelial cells and (iii) investigate manipulation of host cell signaling cascades by T. pallidum adhesins to understand how these proteins are involved in T. pallidum pathogenesis. The invasive capability of T. pallidum is crucial to the development of the serious sequelae of infectious and congenital syphilis, and elimination of treponemal dissemination must be a central target of a syphilis vaccine. An in-depth understanding of the mechanisms used by T. pallidum to disseminate within the host will reveal the optimal syphilis vaccine candidates.
Leptospirosis is prevalent in tropical climates, particularly in urban slum settings, and is considered the world’s most widespread zoonotic disease. Leptospira spp. are shed in the urine of reservoir hosts, including rats, and infections result from direct exposure to urine from infected mammals or urine-contaminated water. Our research uses proteomic approaches to identify leptospiral proteins that are essential for host infection.
Syphilis remains prevalent in low- and middle-income countries and has been on the rise in high-income countries since the year 2000, emphasizing the need for development of an effective vaccine to complement public health approaches for disease elimination. Through our ongoing research projects we identify proteins that are critical for the treponemal infectious process and work towards translating these discoveries into viable vaccine candidates for disease prevention.
Timely diagnosis of syphilis is critical for preventing disease development and transmission, as well as for preventing HIV transmission and acquisition. In our laboratory we perform genomic and proteomic investigations to identify promising diagnostic candidates with the goal of developing direct and indirect syphilis diagnostic tests that perform better than the current gold standard syphilis diagnostic tests.