Members
Herve Agaisse
Hervé Agaisse is an Associate Professor in the Department of Microbiology, Immunology, and Cancer Biology. His laboratory investigates the mechanisms supporting the development and propagation of the intracellular pathogens, Shigella flexneri and Listeria monocytogenes, in the human intestine. These unrelated bacterial pathogens invade intestinal cells and gain access to the cytosolic compartment, where they manipulate the host cell actin cytoskeleton and display actin-based motility. As they reach the cell periphery, motile pathogens form plasma membrane protrusion that project into adjacent epithelial cells, where protrusions resolve into vacuoles. As the pathogens escape from the formed vacuoles, they gain access to the cytosol of adjacent cells, thereby achieving cell-to-cell spread. In the past few years, using RNAi-based genetic approaches, Dr. Agaisse’s group has systematically explored the host cell genes supporting pathogen spread from cell to cell. In addition to the genes coding for the factors required for reconstitution of actin-based motility in vitro, his genetic studies in intestinal cells led to the identification of genes required for efficient intracellular motility in vivo. Moreover, Dr. Agaisse uncovered host cell genes that are not required for actin-based motility, but are essential for efficient cell-to-cell spread. These newly identified genes support the formation and resolution of plasma membrane protrusions at the cell periphery. Altogether, these comparative studies with Shigella flexneri and Listeria monocytogenes uncovered the previously unappreciated notion that, although displaying similar strategies of actin-based motility in the cytosol of infected cells, these intestinal pathogens have evolved strikingly different mechanisms of formation and resolution of membrane protrusions. In addition to the study of bacterial pathogens, his group also explores the mechanisms supporting action-based motility of viral pathogens, such as vaccinia virus. These mechanistic investigations are critical to understanding how pathogens of global infectious potential survive and replicate in their hosts.
Research Area(s): Shigella Listeria
Hervé Agaisse is an Associate Professor in the Department of Microbiology, Immunology, and Cancer Biology. His laboratory investigates the mechanisms supporting the development and propagation of the intracellular pathogens, Shigella flexneri and Listeria monocytogenes, in the human intestine. These unrelated bacterial pathogens invade intestinal cells and gain access to the cytosolic compartment, where they manipulate the host cell actin cytoskeleton and display actin-based motility. As they reach the cell periphery, motile pathogens form plasma membrane protrusion that project into adjacent epithelial cells, where protrusions resolve into vacuoles. As the pathogens escape from the formed vacuoles, they gain access to the cytosol of adjacent cells, thereby achieving cell-to-cell spread. In the past few years, using RNAi-based genetic approaches, Dr. Agaisse’s group has systematically explored the host cell genes supporting pathogen spread from cell to cell. In addition to the genes coding for the factors required for reconstitution of actin-based motility in vitro, his genetic studies in intestinal cells led to the identification of genes required for efficient intracellular motility in vivo. Moreover, Dr. Agaisse uncovered host cell genes that are not required for actin-based motility, but are essential for efficient cell-to-cell spread. These newly identified genes support the formation and resolution of plasma membrane protrusions at the cell periphery. Altogether, these comparative studies with Shigella flexneri and Listeria monocytogenes uncovered the previously unappreciated notion that, although displaying similar strategies of actin-based motility in the cytosol of infected cells, these intestinal pathogens have evolved strikingly different mechanisms of formation and resolution of membrane protrusions. In addition to the study of bacterial pathogens, his group also explores the mechanisms supporting action-based motility of viral pathogens, such as vaccinia virus. These mechanistic investigations are critical to understanding how pathogens of global infectious potential survive and replicate in their hosts.
Huiwang Ai
Molecular Physiology and Biological Physics
School of Medicine
Dr. Ai's lab is engineering fluorescent proteins, luciferases, and unnatural-amino-acid-containing proteins and viruses for imaging, diagnostics, and therapeutics. In addition to protein and viral engineering, we use a collection of innovative techniques, such as fluorescence microscopy, bioluminescence imaging, synthetic chemistry, and electrophysiology, to dissect signaling pathways involving redox-active molecules, chemical transmitters, and protein post-translational modifications (PTMs). In particular, we take advantage of reactive oxygen species and oxidation-induced PTMs to tackle pathogens, either directly or by breaking immune tolerance.
Molecular Physiology and Biological Physics
School of Medicine
Dr. Ai's lab is engineering fluorescent proteins, luciferases, and unnatural-amino-acid-containing proteins and viruses for imaging, diagnostics, and therapeutics. In addition to protein and viral engineering, we use a collection of innovative techniques, such as fluorescence microscopy, bioluminescence imaging, synthetic chemistry, and electrophysiology, to dissect signaling pathways involving redox-active molecules, chemical transmitters, and protein post-translational modifications (PTMs). In particular, we take advantage of reactive oxygen species and oxidation-induced PTMs to tackle pathogens, either directly or by breaking immune tolerance.
Janis Antonovics
Research in my lab is on the evolution and epidemiology of infectious disease in natural populations. Current research questions focus on the role of diseases in determining species range limits, host-pathogen co-evolution, and the evolution of transmission mode. The research combines theoretical modeling with empirical research on sexually transmitted diseases of plants (anther smut) and analysis of datasets involving diseases of organisms ranging from bumble-bees to humans. Antonovics Lab
Research in my lab is on the evolution and epidemiology of infectious disease in natural populations. Current research questions focus on the role of diseases in determining species range limits, host-pathogen co-evolution, and the evolution of transmission mode. The research combines theoretical modeling with empirical research on sexually transmitted diseases of plants (anther smut) and analysis of datasets involving diseases of organisms ranging from bumble-bees to humans. Antonovics Lab