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Many medically relevant bacterial pathogens engage their hosts in an intricate biochemical
cross-talk. My laboratory is interested in using the tools of biochemistry, structural and
cell biology to examine the targeting of host machineries by bacterial virulence factors.
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Bacterial pathogens achieve the internalization of a multitude of virulence factors into eukaryotic cells. Some secrete extracellular toxins which bring about their own entry, usually by hijacking cell surface receptors and endocytic pathways. Others possess specialized secretion and translocation systems to directly inject bacterial proteins into the host cytosol. We are studying both mechanisms, focusing primarily on delivery by the specialized protein Type III secretion system of Gram negative bacterial pathogens.
 Sample Project
Chaperone Movie 1
Chaperone Movie 2
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A very common theme in bacterial pathogenesis is that of manipulation of the host cell
structure, and in particular, by modulating the eukaryotic cytoskeleton. By altering the
structure of cells, bacteria are able to induce their uptake into normally non-phagocytic
host cells, or prevent their uptake into professional phagocytes. In some cases,
internalized bacteria remodel elements of the actin cytoskeleton and microtubule networks
for purposes ranging from the creation and maintenance of a specialized intracellular vacuole
to the propulsion within and between cells. In the least sophisticated instances, bacteria
can use toxins to irreversibly alter host cytoskeletal structure, often with death of the
eukaryotic cell.
Sample Project 1
Sample Project 2
Sample Project 3
Salmonella Invasion of Host Cells
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Bacteria have been found to both directly and indirectly target the eukaryotic cell cycle, leading to both stimulatory (pro-cell cycle progressing) and inhibitory (cell cycle arrest) effects. These effects are thought to aid in bacterial dissemination as well as suppress proliferative-dependent processes in the innate and acquired immune system.
Sample Project
CDT Holotoxin Movie
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Bacteria have been found to modulate host programmed cell death pathways through a variety of factors. This has been especially true for bacterial pathogens of plants, as plants utilize a defense mechanism, the Hypersensitive Response, a key component of which is programmed cell death localized to the infection site. Animal pathogens are also known to modulate host programmed cell death for their own benefit, targeting, for example, caspases and the mitochondria.
Sample Project
AvrPtoB Movie
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Bacteria have and are constantly evolving and exchanging mechanisms to resist the activity
of antibiotics. This has led to a crisis in medical care, in which many pathogens are
multi-drug resistant, and the specter is raised of a "post-antibiotic" world. There is a
great need for novel pharmacological interventions in bacterial infection, and modern
pharmaceutical companies are currently scaling back such efforts or closing them down completely.
Academic groups, therefore, have an important role to play in contributing to the next generation
of anti-bacterial drugs. We are interested in the possibility of virulence inhibitors serving as
therapeutic agents, and are using computational and chemical screening to identify such compounds.
Sample Project
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