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Assistant Professor
Center for Infectious Disease Research and Vacciniology, Departments of Veterinary Science and Biology/Microbiology
Philip.Hardwidge@sdstate.edu
Phone: (605) 688-5259
Fax: 605-688-6003
Research Publications
EDUCATION
- Postdoctoral fellow, University of British Columbia, Vancouver, Canada (2002-2005) Proteomic profiling of host-pathogen interactions. Advisor: B. Brett Finlay
- Ph.D., Biomedical Sciences, Mayo Clinic, Rochester, MN (2002) Electrostatics in DNA-protein interactions. Advisor: L. James Maher
- B.S., Microbiology, University of Illinois, Urbana, IL (1997)
I am currently accepting highly motivated undergraduate students, graduate students, and postdoctoral fellows to join a dynamic, productive, multidisciplinary research group focused on the understanding, treatment, and prevention of diarrheagenic E. coli disease.
BACKGROUND
Escherichia coli (E. coli) is a bacterium commonly found in human gut and in other warm-blooded animals. While most strains of E. coli are harmless, some cause severe disease.
Our laboratory studies several forms of E.coli that cause diarrhea and malnutrition in humans and livestock, including ETEC, EPEC, and EHEC. These strains are transmitted by food or water contaminated with animal or human feces. Each strain produces special toxin(s) that stimulate the secretion of excess fluid in the intestine, causing diarrhea.
Enterotoxigenic E. coli, (ETEC) is the leading cause of travelers' diarrhea and a major cause of diarrheal disease in underdeveloped nations, especially among children. ETEC is also increasingly recognized as an important cause of food borne illness in developed nations.
Enteropathogenic E. coli (EPEC) is the leading cause of bacterial mediated diarrhea in young children and, like ETEC, poses a major endemic health threat in developing countries.
Enterohemorrhagic E. coli (EHEC) causes a more severe diarrhea than EPEC or ETEC due to its production of an additional toxin (Shiga-like toxin). EHEC is an important problem health problem in the United States and is commonly transmitted through raw or undercooked ground meat products (Hamburger Disease). Infection may develop, especially in young children and the elderly, into a fatal kidney disease known as haemolytic uremic syndrome (HUS),
EPEC and EHEC use a ‘molecular syringe’, known as a ‘type III secretion apparatus’, to inject bacterial proteins directly into the cytoplasm of a host cell to which they have bound. Once inside the host cell, these bacterial proteins, known as ‘effectors’ contribute to disease by modulating the normal activity of the host. ETEC uses a different mechanism to bind to the intestinal epithelium and has a different repertoire of bacterial toxins.
We hope to contribute to a greater understanding of the pathogenesis of diarrheagenic E. coli and ultimately help to guide the development of future vaccines and antibiotics.
Potential research projects include, but are not limited to:
- Biochemical dissection of the EPEC effector EspG
- Cell biological analysis of the EHEC effector NleF
- Comparative in vivo proteomics of infected host cells
- Complete genome sequencing of ETEC virulence plasmids
- Contribution of ETEC toxins to in vivo colonization dynamics
- Discovery of novel ETEC virulence factors
- DNA-binding properties of bacterial regulatory proteins
- Genetic basis of bacterial resistance in swine
- Microarray analysis of bacterial virulence factor expression
- Modulated eukaryotic signalling pathways in infected host cells
- Novel bacterial GTPases as potential new drug targets
- Three-dimensional imaging of in vivo EHEC lesions
- Yeast as a model organism to study E. coli virulence proteins
LINKS
SDSU Homepage
CIDRV 
Veterinary Science Department
Biology and Microbiology Department
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