Most Significant Research Contributions

About | Achievements and Awards | Most Significant Research Contributions | Affiliated Institutions

1986

Molecular biology of F-like pili and conjugation, including defining oriT, surface exclusion, pilus type, and finOP systems.

1988

Salmonella interactions with cultured cells, including the first use of polarized epithelial barriers and bacterial infection to study transcytosis.

1991

Fluorescence and confocal microscopy of actin cytoskeletal rearrangements underlying invading Salmonella.  This was the first observation of ruffles and the role of the host cytoskeleton, and the first use of confocal microscopy to study “cellular microbiology”.

1992

By using tyrosine kinase inhibitors and anti-phosphotyrosine antibodies, we demonstrated for the first time the role of phosphotyrosine and other signals in host-pathogen interactions.

1993

Identified Salmonella induced filaments (Sifs) that are needed for intracellular survival and replication, and virulence.

1995

First characterized the intracellular routing of the Salmonella containing vacuole (SCV) and demonstrated it was different than a phagosome-lysosome compartment.

Identified the Esp secreted proteins of EPEC, which represent a new and essential family of virulence factors for these pathogens.

1996

Characterized several Esps.

Defined several host cell signal transduction events involved in E. coli and Salmonella pathogenesis.

1997

Used confocal microscopy to study a realistic low dose mouse infection model by Salmonella.  This was the first time early events in an infection could be studied, proving that this pathogen was intracellular, and induced macrophage apoptosis in vivo.

Discovered Tir, a bacterial protein that is inserted into host cell membranes where it then binds to intimin on EPEC’s surface, and the cytoskeleton at its cytoplasmic face.  This was the first identification of a pathogen that inserts its own receptor into host cells.

1998

Isolated SCVs for the first time to study intracellular vacuole routing.

Showed that the Esps were virulence factors in a relevant animal model.

1999

Used FACS analysis to study the SCV to demonstrate it traffics through early endosomes and then occupies a specialized compartment.

Showed that Wasp and Arp2/3 are involved in EPEC pedestal formation.

2000

Identified SifA as a member of type III secreted effectors, and showed it is necessary for intracellular survival in macrophages.

Used gene arrays to study Salmonella-macrophage interactions and host cell response, the first time such technology was used for this purpose.

Demonstrated that Tir binds alpha-actinin directly, the first host cell molecule identified that binds Tir.

Determined the cocrystal structure of Tir complexed with intimin, the first structure of an adhesin bound to its receptor.

2001

Developed bovine 0157 vaccine, which protects cattle from 0157 colonization and shedding.

Determined (with Dr. Natalie Strynadka) the first type III secretion system chaperone structures (CesT and SigE).

Demonstrated that Tir phosphotyrosine binds Nck adaptor, which is essential for cytoskeleton rearrangements and pedestals.

2002

Defined the first hybrid pathogenicity island (contains both Spi-1 and Spi-2 effectors).

Demonstrated for the first time that there are interactions between a host resistance gene (NRAMP) and virulence factors (Spi-2).

Identified and characterized several new Spi-2 effectors.

2003

Demonstrated that although Tir is a virulence factor, it does not have to be tyrosine phosphorylated.

Determined there are varying susceptibilities in mice to Citrobacter rodentium.

Published studies showing a bovine vaccine against O157 prevents shedding in cattle.

2004

Defined a major mechanism by which macrophages control Salmonella and how it counters it.

Used systems biology to assign functions to all 41 pathogenic E. coli LEE genes.

Defined the proteomic host response to pathogenic E. coli.

Developed a SARS vaccine.

First structure of a type III effector with chaperone.

2005

Developed the rapid response/emergency management plan for emerging infectious diseases.

Developed a Salmonella gastroenteritis model.

2006

Developed a method to rank human virulence potential of enterohemorrhagic E. coli strains

Evaluated two SARS vaccines

2007

First structure of a type III secretion system ATPase

Described a molecule that modulates innate immunity to treat infections

Established a transmission model of infection, and showed it needs virulence factors

Showed that inflammation disrupts intestinal microbiota which impacts on infection

2008

Received regulatory approval for full commercialization of the E. coli 0157 Bovine Vaccine in Canada, approval of process for conditional licensing in US

2009

Developed prototype non-typhoidal Salmonella vaccine and second generation E. coli O157 vaccine

Established models to modulate microbiota and its impact on infection and immune responses

2010

Established the role of microbiota in enteric diseases, including fecal transfers as a way to alter host resistance to disease.  Defined the role of microbiota on host metabolics.

2011

Identified particular microbiota involved in mediating enteric infections.  Demonstrated that microbiota affect asthma, including identifying particular microbes and accompanying immune mechanism.

2012

Demonstrated the role of metabolites from both the host and microbiota on pathogen virulence mechanisms, affecting virulence outcome.

2013

Identified the link between inflammasomes and mucous secretion, including its role in defines against enteric pathogens