Faculty

• Harborview Medical Center


• Physical Address:
• 300 9th Ave
• R&T Building, Room 411
• Seattle, WA 98104


• Mailing Address
• 300 9th Ave
• Box 359779
• Seattle, WA 98104


• Telephone: (206) 897-5402
• Fax: (206) 897-5363


• Email: giacal@u.washington.edu

Lorenzo Giacani, PhD

• Assistant Professor of Medicine, Division of Allergy and Infectious Diseases
  University of Washington

During syphilis infection, T. pallidum replication within primary and secondary lesions triggers a strong inflammatory response that attracts macrophages, lymphocytes and plasma cells to the site of infection. Following the appearance of an adaptive host immune response, the majority of T. pallidum cells are cleared by opsonophagocytosis, and lesions spontaneously resolve, leading to the asymptomatic stage of the disease known as latency. Despite the host’s efficient eradication, a few T. pallidum cells avoid immune clearance and persist in the host. In absence of treatment, this smoldering persistence can cause recrudescence of early symptoms or, after prolonged latency, trigger disease reactivation and progression to its tertiary stage, characterized by manifestations such as gummatous disease, cardiovascular syphilis, general paresis, or tabes dorsalis.

Dr. Giacani's work at the University of Washington focuses on the role f T. pallidum sigma (σ) factors in inducing transcriptional modifications that help the pathogen counteract the host defenses and persist in the face of an active immune response. Bacterial σ factors are proteins required for initiation of RNA synthesis that transiently bind the core RNA polymerase (cRNAP) to transcribe specific groups of genes (called regulons), each controlling a subset of cellular functions. In the rabbit model of primary syphilis, transcription of T. pallidum σ factors associated with stress response and motility (σ24 and σ28, respectively) is significantly up-regulated at the time of immune clearance with respect to all other T. pallidum σ factors, predicted to control housekeeping functions (σ70 and σ43) and nitrogen metabolism (σ54). This evidence suggests a possible causal link between σ24 and σ28 up-regulation and the appearance of phagocytosis-resistant T. pallidum cells. The implications of σ24 and σ28 up-regulation for the pathogenesis of syphilis are currently being investigated in collaboration with Drs. Sheila Lukehart and Arturo Centurion-Lara. In addition, Dr. Giacani is currently investigating T. pallidum natural competence for uptake of exogenous DNA to be used as substrate for homologous recombination.

Selected Publications

Centurion-Lara A., Giacani L., Godornes C., Molini B.J., Brinck Reid T., and Lukehart S.A. (2013). Fine Analysis of Genetic Diversity of the tpr Gene Family among Treponemal Species, Subspecies and Strains. PLoS NTD, Accepted.

Giacani, L., Tompa, M., Denisenko, O., Lukehart, S.A., and Centurion-Lara, A. (2013). Identification of the Treponema pallidum subsp. pallidum TP0092 (s24) Regulon: implications for pathogen persistence in the host and syphilis pathogenesis. Molecular Microbiology. Journal of Bacteriology, 195, 4, 896-907.
[ PubMed Abstract ]

Giacani, L., Brandt, S.L., Puray-Chavez, M., Brinck Reid, T., Godornes, C., Molini, B.J., Lukehart, S.A., & Centurion-Lara, A.(2012). Comparative investigation of the genomic regions involved in antigenic variation of the TprK antigen among treponemal species, subspecies, and strains. Journal of Bacteriology, 194, 16, 4208-25.
[ PubMed Abstract ]

Giacani, L., Chattopadhyay, S., Centurion-Lara, A., Jeffrey, B.M., Le, H.T., Molini, B.J., Lukehart, S.A., Sokurenko, E., & Rockey, D,D. (2012). Footprint of positive selection in Treponema pallidum subsp. pallidum genome sequences suggests adaptive microevolution of the syphilis pathogen. PLoS NTD, 6, 6, e1698.
[ PLoS Abstract ]

Giacani, L., Jeffrey, B.M., Molini, B.J., Le, H.T., Lukehart, S.A., Centurion-Lara, A., & Rockey D.D. (2010). Complete genome sequence and annotation of the Treponema pallidum subsp. pallidum Chicago strain. Journal of Bacteriology, 192, 2645-6.
[ PubMed Abstract ]

Giacani, L., Molini, B.J., Kim, E.Y., Godornes, C., Leader, B.T., Centurion-Lara, A., & Lukehart, S.A. (2010). Antigenic variation in Treponema pallidum: TprK sequence diversity accumulates in response to immune pressure during experimental syphilis. Journal of Immunology, 2010, 184, 3822-9.
[ PubMed Abstract ]

 

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