Faculty
Philip R. Hardwidge
B.S. 1997, University of Illinois, Urbana
Ph.D. 2002, Mayo Clinic Graduate School
Associate Professor
Phone:(785) 532-2506
Fax: (785) 532-4851
Email: hardwidg@vet.k-state.edu
Research
Our laboratory is focused on understanding, treating, and preventing diarrheal disease caused by bacterial pathogens. We study several types of Escherichia coli that cause diarrhea and malnutrition in humans and livestock. We have discovered novel molecular mechanisms by which bacterial proteins subvert the innate immune system of the host to promote bacterial colonization and transmission. We are also developing, in collaborative studies, novel proteomic techniques for identifying bacterial vaccine targets.
Hardwidge PR, Rodriguez-Escudero I, Goode D, Donohoe S, Eng J, Goodlett DR, Aebersold R, Finlay BB. Proteomic analysis of the intestinal epithelial cell response to enteropathogenic Escherichia coli. Journal of Biological Chemistry. 2004 May 7;279(19):20127-36. PMID: 14988394
Deng W, Li Y, Hardwidge PR, Frey EA, Pfuetzner RA, Lee S, Gruenheid S, Strynakda NC, Puente JL, Finlay BB. Regulation of type III secretion hierarchy of translocators and effectors in attaching and effacing bacterial pathogens. Infection and Immunity. 2005 Apr;73(4):2135-46. PMC1087438 (featured on Faculty of 1000)
Hardwidge PR, Deng W, Vallance BA, Rodriguez-Escudero I, Cid VJ, Molina M, Finlay BB. Modulation of host cytoskeleton function by the enteropathogenic Escherichia coli and Citrobacter rodentium effector protein EspG. Infection and Immunity. 2005 May;73(5):2586-94. PMC1087329
Kim J, Thanabalasuriar A, Chaworth-Musters T, Fromme JC, Frey EA, Lario PI, Metalnikov P, Rizg K, Thomas NA, Lee SF, Hartland EL, Hardwidge PR, Pawson T, Strynadka NC, Finlay BB, Schekman R, Gruenheid S. The bacterial virulence factor NleA inhibits cellular protein secretion by disrupting mammalian COPII function. Cell Host and Microbe. 2007 Sep 13;2(3):160-71. PMID: 18005731 (featured on Faculty of 1000)
Gao X, Wan F, Mateo K, Callegari E, Wang D, Deng W, Puente J, Li F, Chaussee MS, Finlay BB, Lenardo MJ, Hardwidge PR. Bacterial effector binding to ribosomal protein S3 subverts NF-êB function. PLoS Pathogens 2009. Dec;5(12):e1000708. PMC2791202
Johnson AM, Kaushik RS, Francis DH, Fleckenstein JM, Hardwidge PR. Heat-labile enterotoxin promotes Escherichia coli adherence to intestinal epithelial cells. Journal of Bacteriology. 2009 Jan;191(1):178-86. PMC2612432
Fleckenstein JM, Hardwidge PR, Munson G, Rasko D, Sommerfelt H, Steinsland H. Molecular mechanisms of enterotoxigenic Escherichia coli infection, Microbes and Infection, 2010. Feb;12(2):89-98. PMID: 19883790
Shames SR, Deng W, Guttman JA, deHoog CL, Li Y, Hardwidge PR, Sham HP, Vallance BA, Foster LJ, Finlay BB. The pathogenic E. coli type III effector EspZ interacts with host CD98 and facilitates host cell prosurvival signaling. Cellular Microbiology, 2010, Sep 1; 12(9):1322-39. PMID: 20374249
Wan F, Weaver A, Gao X, Bern M, Hardwidge PR, Lenardo MJ. IKKâ phosphorylates RPS3 to regulate its nuclear translocation and NF-kB specifier function, Nature Immunology 2011 Apr;12(4):335-43. PMID: 21399639 (featured on Faculty of 1000)
Wang X, Gao X, Hardwidge PR. Heat-labile enterotoxin-induced activation of NF-kappaB and MAPK pathways in intestinal epithelial cells impacts enterotoxigenic Escherichia coli (ETEC) adherence, Cellular Microbiology, 2012 Aug;14(8):1231-41. PMID: 22452361
Pham T, Gao X, Tsai K, Olsen R, Wan F, Hardwidge PR. Functional differences and interactions between the E. coli type III secretion system effectors NleH1 and NleH2, Infection & Immunity, 2012 Jun;80(6):2133-40. PMID: 22451523