Daniele Provenzano
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ProfessorDepartment of BiologyJoint appointment: School of Earth, Environmental, and Marine Sciences
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EducationPostdoctoral Fellow, Harvard Medical School |
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Areas of Interest
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Courses
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Research OverviewVibrio cholerae is the causative agent of cholera, a devastating and potentially lethal form of diarrhea that persists as a significant cause of morbidity and mortality in the developing world. While only a subset of V. cholerae strains encode genes for the virulence factors Cholera Toxin (CT) and Toxin-Coregulated Pilus (TCP) required for pandemic spread, all cholera bacteria and 25% of all Proteobacteria harbor genes coding a type VI secretion system (T6SS). T6SS gene products assemble into a dynamic molecular puncturing device in the cytosol of bacteria to deliver defector molecules (toxins) into adjacent cells. Three effector molecules have been identified in V. cholerae along with cognate immunity proteins that protect kin bacteria from T6SS-mediated killing. Effector/immunity pairs appear to be horizontally mobilized within otherwise highly conserved T6SS gene clusters. Examination of V. cholerae strains endemic to the lower Rio Grande Delta led to the discovery of a wide range of effector/immunity pair alleles indicating that, in addition to interspecies competition, cholera bacteria also engage their T6SS in intraspecies competition. T6SS-mediated intraspecies competition is linked to V. cholerae’s ability to colonize the human host because nearly all strains that harbor CT and TCP (which reside on horizontally mobilized genetic elements CT-phage and VPI respectively) possess the same T6SS effector/immunity alleles. Characterization of novel episomal genetic elements and whole genome sequence data mining of V. cholerae strains endemic to the lower Rio Grande Delta as well as explorations of applications for therapeutic intervention strategies based on these T6SS discoveries are on-going. |
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Recent Publications
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