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Research Description: The laboratory is predominantly set to investigate vector-borne disease pathogenesis, with a strong emphasis on tick-borne infectious agents and intracellular bacteria in the order Rickettsiales. We employ multidisciplinary approaches toward scientific investigation ranging from simple diagnostic methods for clinical purposes, to molecular, genomic and epigenetic approaches for fundamental scientific discovery. Most basic work focuses on Anaplasma phagocytophilum AnkA, a type IV secretion system substrate that epigenetic regulates host chromatin and nuclear structure to influence eukaryotic gene transcriptional programs by binding gene promoters in cis and by binding chromatin into the nuclear lamina in trans. Additional investigations in the lab focus on i) Rickettsia, Anaplasma, Ehrlichia, and Borrelia infections and immunopathology mediated by NKT and cytotoxic T cells; ii) A. phagocytophilum immunopathology related to NKT, NK, and CD8 T cells immune responses; iii) Stat1 signaling and its role in immunopathology with A. phagocytophilum infection. We also study tick-borne co-infections and their synergistic pathogenetic mechanisms with Lyme disease and human granulocytic anaplasmosis. Because an underlying tenet of infection pathogenesis with many vector-borne pathogens is increased vascular permeability or access to the vasculature for systemic dissemination, we also study, pathogen endothelial cell barrier intravasation, invasion, dissemination, extravasation, and vascular permeability by Borrelia, Rickettsia, Ehrlichia and other pathogens in vitro and in vivo. These studies focus in part on the roles of intracellular calcium concentrations, divalent cation chelators, phospholipase C inhibitors and antagonists of signaling through G protein-coupled receptors that prevent increases in vascular barrier permeability. Finally, the laboratory supports clinical investigations of febrile disease etiology in under-resourced regions, including Malaysia, Sri Lanka, Nicaragua, Tanzania, among other locations. These studies focus on high-throughput and multiplexed methods for molecular diagnosis and avoidance of misdiagnosis to prevent inappropriate treatment and the consequent negative outcomes. The aims are to i) answer how much fever in such regions is the result of undiagnosed rickettsial disease, and ii) implement clinical studies and trials of new diagnostic tests, therapies and vaccines to prevent these vector-borne infections.
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Andres F. Londono, Jennifer M. Farner, Marlon Dillon,Dennis J. Grab,Yuri Kim,Diana G. Scorpio,J. Stephen Dumler
PLOS NEGLECTED TROPICAL DISEASESno. 2 (2024): e0011993-e0011993
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Jyan Lucas Benevenute,John Stephen Dumler,Maria Ogrzewalska,Andre Luiz Rodrigues Roque, Victoria Valente Califre Mello,Keyla Carstens Marques de Sousa,Luiz Ricardo Goncalves,Paulo Sergio D'Andrea,Elba Regina de Sampaio Lemos,Rosangela Zacarias Machado,Marcos Rogerio Andre
TICKS AND TICK-BORNE DISEASESno. 6 (2023)
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Yuri Kim,Emily G. Clemens, Jennifer M. Farner,Andres Londono-Barbaran,Dennis J. Grab,J. Stephen Dumler
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2023): 96-103
Jyan Lucas Benevenute,John Stephen Dumler,Maria Ogrzewalska,André Luiz Rodrigues Roque, Victoria Valente Califre Mello,Keyla Carstens Marques de Sousa,Luiz Ricardo Gonçalves,Paulo Sérgio D'Andrea, Elba Regina de Sampaio Lemos,Rosangela Zacarias Machado,Marcos Rogério André
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2023): 1187267
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