BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Tarr, Phillip I. Professor of Pediatrics and Molecular Microbiology eRA COMMONS USER NAME TARR_P EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) DEGREE INSTITUTION AND LOCATION YEAR(s) FIELD OF STUDY (if applicable) Brown University, Providence, RI A.B. 1975 Biology Yale University, New Haven, CT M.D. 1980 Medicine University of Washington, Seattle, WA Resident 1980-1983 Pediatrics A. Positions and Honors.Positions and Employment1983-1987 Infectious Diseases Fellowship, University of Washington, Seattle, WA1986-1987 Research Associate, Seattle Biomedical Research Institute, Seattle, WA1988-1989 Gastroenterology Fellowship, University of Washington, Seattle, WA1989-1995 Assistant Professor, Pediatrics (Gastroenterology)1995-1998 Associate Professor, Pediatrics (Gastroenterology), Adjunct Associate Professor, Microbiology1998-2003 Professor, Pediatrics (Gastroenterology), Adjunct Professor, Microbiology2003- Affiliate Professor of Pediatrics and Microbiology, University of Washington School of Medicine2003- Professor of Pediatrics and Molecular Microbiology, Washington University School of MedicineOther Experience and Professional MembershipsInfectious Diseases Society of America (Fellow)American Gastroenterological AssociationAmerican Society for MicrobiologyNorth American Society for Pediatric Gastroenterology and NutritionSociety for Pediatric ResearchHonors1992-1995 American Gastroenterological Association/Blackwell Scientific Research Scholar Award1997 Food and Drug Administration Commissioner’s Special Citation2004- Election, American Pediatric Society2004 Endowed Chair Recipient, Melvin E. Carnahan ProfessorshipB. Selected peer-reviewed publications (in chronological order). (Selected from 84 peer-reviewedpublications)1. Ostroff, S., Tarr, P.I., Neill, M.A., Lewis, J.H., Hargrett-Bean, N., Kobayashi, J.M., Toxin genotypes and plasmid profiles as determinants of systemic sequelae in Escherichia coli 0157:H7 infections. J Infect Dis 160:994, 1989.2. Montgomery, K.F., Osborn, L., Hession, C., Tizard, R., Goff, D., Vassalo, C., Tarr, P.I., Bomsztyk, K., Lobb, R., Harlan, J., Pohlman, T. Activation of endothelial-leukocyte adhesion molecule 1 (ELAM-1) gene transcription. Proc Nat Acad Sci (USA) 88:6523, 1991.3. Paros, M., Tarr, P.I., Kim, H., Besser, T.E., Hancock, D.D. A comparison of human and bovine Escherichia coli O157:H7 isolates by toxin genotype, plasmid profile, and bacteriophage λ-RFLP profile. J Infect Dis 168:1300, 1993.4. Bell, B.P., Goldoft, M., Griffin, P.M., Davis, M.A., Gordon, D.C., Tarr, P.I., Bartleson, C.A., Lewis, J., Barrett, T.J., Wells, J.G., Baron, R., Kobayashi, J. A multistate outbreak of Escherichia coli O157:H7- associated bloody diarrhea and hemolytic uremic syndrome from hamburgers: the Washington experience. JAMA 272:1349, 1994.5. Kim, H., Samadpour, M., Grimm, L., Clausen, C.R., Besser, T.E., Baylor, M., Kobayashi, J.M., Neill, M.A., Schoenknecht, F.D., Tarr, P.I. Characteristics of antibiotic resistant Escherichia coli O157:H7 in
Washington State, 1984 - 1991. J Infect Dis 170:1606, 1994.6. Bilge, S.S., Vary, J.C. Jr., Dowell, S.F., Tarr, P.I. Rose of the Escherichia coli O157:H7 O side chain in adherence and analysis of an rfb locus. Infect Immun 64:4795, 1996.7. Bokete, T.N., Whittam, T.S., Wilson, R.A., Clausen, C.R., O’Callahan, C.M., Moseley S.L., Fritsche, T.R., Tarr, P.I. Genetic and phenotypic analysis of Escherichia coli with enteropathogenic characteristics isolated from Seattle children. J Infect Dis 175:1382, 1997.8. Desmarchelier, P.M., Bilge, S.S., Fegan, N., Mills, L., Vary, J.C. Jr, Tarr, P.I. A PCR specific for Escherichia coli O157 based on the rfb locus encoding O157 lipopolysaccharride. J Clin Microbiol 36:1801, 19989. Schmidt, H., Geitz, C., Tarr, P.I., Frosch, M., Karch, H. Non-O157:H7 pathogenic Shiga toxin-producing Escherichia coli: Phenotypic and genetic profiling of virulence traits and evidence for clonality. J Infect Dis 179:115, 1999.10. Kudva, I.T., Jelacic, S., Tarr, P.I., Youderian, P.A., Hovde, C.J. Biocontrol of Escherichia coli O157 with O157-specific bacteriophages. Appl Environ Microbiol 65:3767, 1999.11. Lee, D.K., Tarr, P.I., Haigh, W.G., Lee, S.P. Bacterial DNA in mixed cholesterol gallstones. Am J Gastroenterol 94:3502, 1999.12. Tarr, P.I., Bilge, S. S. Vary, Jr., J.C., Jelacic, S., Habeeb, R.L., Ward, T.R., Baylor, M.R., Besser, T.E. Iha: A novel Escherichia coli O157:H7 adherence-conferring molecule encoded on a chromosomal region of conserved structure. Infect Immun 1400, 2000.13. Wong, C.S., Jelacic, S., Habeeb, R.L., Watkins, S.L., Tarr, P.I. The risk of hemolytic uremic syndrome after antibiotic treatment for Escherichia coli O157:H7 infections. N Engl J Med 342:1930, 2000.14. Tarr, P. I., Schoening, L. M., Yea, Y. L., Ward, T. R., Jelacic, S., Whittam, T. S. Acquisition of the rfb-gnd gene cluster in the evolution of pathogenic Escherichia coli O55 and O157. J Bacteriol 182:6183-6191 2000.15. Schmidt, H., Zhang, W.L., Hemrich, U., Jelacic, S., Brunder, W., Tarr, P.I., Hacker, J., Karch, H. The Locus of Protease Activity (LPA) –Functional and Evolutionary Analysis of a Novel Chromosomal Island in Shiga Toxin 2d-producing Escherichia coli. Infect Immun 69:6863-6873, 2001.16. Chandler, W.L, Jelacic, S., Boster, D.R., Ciol, M., Williams, G.D., Watkins, S.L., Igarashi, T., Tarr, P.I. Prothrombotic Coagulation Abnormalities Associated with Escherichia coli O157:H7 infections. N Engl J Med 346:23-32, 2002.17. Jelacic, S., Wobbe, C.L., Boster, D.R., Ciol, M.A., Watkins, S.L., Tarr, P.I, Stapleton, A.E. ABO and P1 Blood Group Antigen Expression and stx genotype and outcome of childhood Escherichia coli O157:H7 infections. J Infect Dis 185:214-219, 2002.18. Cornick, N.A., Jelacic, S., Ciol, M.A., Tarr, P.I. Escherichia coli O157:H7 infections: Discordance between filterable fecal shiga toxin and disease outcome. J Infect Dis 186:57-63, 2002.19. Lathem, W.W, Grys, T.E., Tarr, P.I., Welch, R.A. Escherichia coli O157:H7 produces an extracellular metalloprotease, StcE, specific for cleavage of human C1 esterase inhibitor. Mol Microbiol 45:277-288, 2002.20. Klein E.J., Stapp, J.R., Clausen, C.R., Boster, D.R., Jelacic, S., Wells, J.G., Qin, X., Swerdlow, D.L., Tarr, P.I. Shiga toxin-producing Escherichia coli in children with diarrhea: A prospective point of care study. J Pediatr 141:172-177, 2002.21. Lopez-Saucedo C, Cerna JF, Villegas-Sepulveda N, Thompson R, Velazquez FR, Torres J, Tarr PI, Estrada-Garcia TA. Single Multiplex Polymerase Chain Reaction to Detect Diverse Loci Associated with Diarrheagenic Escherichia coli. Emerg Infect Dis 9:127-131, 2003.22. Shaikh N, Tarr PI. Escherichia coli O157:H7 Shiga toxin-encoding bacteriophages: integrations, excisions, and truncations. J Bacteriol 185:3596-3605, 2003.23. Jelacic JK, Damrow T, Chen GS, Jelacic S, Bielaszewska M, Ciol M, Carvalho HM, Melton-Celsa AR, OBrien AD, Tarr PI. Shiga toxin-producing Escherichia coli in Montana: bacterial genotypes and clinical profiles. J Infect Dis 188:719-729, 2003.24. Johnson JR, Lockman HA, Owens K, Jelacic S, Tarr PI. High-frequency secondary mutations after suicide- driven allelic exchange mutagenesis in extraintestinal pathogenic Escherichia coli. J Bacteriol 185:5301-5, 2003.25. Johnson JR, Jelacic S, Schoening LM, Clabots C, Shaikh N, Mobley HL, Tarr PI., The IrgA homologue adhesin Iha is an Escherichia coli virulence factor in murine urinary tract infection. Infect Immun 73:965-71, 2005.
26. John, M, Kudva, IT, Griffin, RW, Dodson, AW, McManus, B, Krastins, B, Sarracino, D, Progulske-Fox, A, Hillman, JD, Handfield, M, Tarr, PI, Calderwood, SB. Identification of Escherichia coli O157:H7 proteins expressed during human infection using in vivo-induced antigen technology (IVIAT). Infect Immun 73:2665-79, 2005.27. Bielaszewska M, Zhang W, Tarr PI, Sonntag AK, Karch H. Molecular profiling and phenotype analysis of Escherichia coli O26:H11 and O26:NM: secular and geographic consistency of enterohemorrhagic and enteropathogenic isolates. J Clin Microbiol 43:4225-8, 2005.28. Ake JA, Jelacic S, Ciol MA, Watkins SL, Murray KF, Christie DL, Klein EJ, Tarr PI. Relative nephroprotection during Escherichia coli O157:H7 infections: association with intravenous volume expansion. Pediatrics 115:e673-680, 2005.29. Klein EJ, Boster DR, Stapp JR, Wells JG, Qin X, Clausen CR, Swerdlow DL, Braden CR, Tarr PI. Diarrhea Etiology In A Children’s Hospital Emergency Department: A Prospective Cohort Study. Clin Infect Dis 43:807-13, 2006.30. Kudva IT, Krastins B, Sheng H, Griffin RW, Sarracino DA, Tarr PI, Hovde CJ, Calderwood SB, Manohar J. Proteomics-Based Expression Library Screening (PELS) – A Novel Method for Rapidly Defining Microbial Immunoproteomes. Mol Cell Proteomics 5:1514-9, 2006.31. Rashid RA, Tarr PI, Moseley SL. Expression of the Escherichia coli IrgA homologue adhesin is regulated by the ferric uptake regulation protein. Microb Pathog 41:207-17, 2006.32. Rashid RA, Tabata TA, Oatley MJ, Besser TE, Tarr PI, Moseley SL. Expression of putative virulence factors of Escherichia coli O157:H7 differs in bovine and human infections. Infect Immun 74:4142-4148, 2006.33. Stahl Al, Svensson M, Morgelin M, Svanborg C, Tarr PI, Mooney JC, Watkins SL, Johnson R, Karpman D. Lipopolysaccharride from enterohemorrhagic Escherichia coli binds to platelets via TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome. Blood. 108(1):167-76, 2006.34. Qin X, Razia Y, Johnson JR, Stapp JR, Boster DR, Tsosie T, Smith DL, Braden CB, Gay K, Angulo FJ, Tarr PI. Ciprofloxacin-resistant Gram-negative Bacilli in the Fecal Microflora of Children. Antimicrob Agents Chemother 50:3325-9, 2006.35. Besser TE, Shaikh N, Holt NJ, Tarr PI, Konkel ME, Malik-Kale P, Whittam T, Bono J. Greater Diversity of Shiga toxin-encoding Bacteriophage Insertion Sites among Escherichia coli O157:H7 Isolates from Cattle than from Humans. Applied and Environmental Microbiology 73:671-679, 2007.36. Shaikh N, Holt NJ, Johnson JR, Tarr PI. Fim operon variation in the emergence of Shiga toxin-producing Escherichia coli: an evolutionary and functional analysis. FEMS Microbiology Lett. 2007 Aug;273(1):58-63.37. Finkbeiner SR, Allred AF, Tarr PI, Klein EJ, Kirkwood CD, Wang D. Metagenomic analysis of human diarrhea: viral detection and discovery. PloS Pathog 4(2):e1000011, 2008. PMID: 18398449.38. Cobbold RN, Davis MA, Rice DH, Szymanski M, Tarr PI, Besser TE, Hancock DD. Associations between bovine, human, and raw milk, and beef isolates of non-O157 Shiga toxigenic Escherichia coli within a restricted geographic area of the United States. J Food Prot 71:023-1027, 2008. PMID: 18522040.39. Hill J, Beriwal S, Chandra I, Paul VK, Kapil A, Singh T, Wadowsky RM, Singh V, Goyal A, Jahnukainen T, Johnson JR, Tarr PI, Vats A. Loop Mediated Isothermal Amplification Assay for Rapid Detection of Common Strains of Escherichia coli. J. Clin Microbiol 46:2800-2804, 2008. PMID: 18550738.40. Laiko M, Zhu C, Gutsal O, Boedeker E, O’Malley R, Cole R, Tarr P, Mooney J, Watkins S, Gibas J, Kane A, Donowitz M, Kovbasnjuk O. Shiga Toxin 1 interaction with intestinal epithelial cells causes galectin-3 apical secretion. Submitted.41. Denno D, Keene W, Hutter C, Duchin J, Koepsell J, Patnode M, Flodin-Hursh D, Rasmussen L, Stewart L, Jones R, Tarr PI. Risk Factors for Sporadic Reportable Bacterial Enteric Infections in Children. Submitted.C. Research SupportOngoing Research SupportR56 AI063282-01 Tarr (PI) 8/15/06-7/31/08NIH/NIAIDNucleotide Polymorphisms in Enteric PathogensThe major goals of the project are:1. Test the hypothesis that SNPs in chromosomal backbones are stable.2. Confirm or refute the hypothesis that bacterial SNPs in backbones of bacterial chromosomes delineate lineage
within pathogenic clades.3. Test the hypothesis that bacterial SNPs in pathogenicity islands can be used to distinguish the origin of strains.4. Confirm or refute the hypothesis that the ECOR Collection phylogeny reliably determines the radiation of members of this species and, in the process, provide precise phylogenetic data regarding branch points.Role: PIRO1 DK052081 Tarr (PI) 2/1/03-6/30/08NIH/NIDDKPathophysiology of Childhood Hemolytic Uremic SyndromeThe major goal of this project are to study the host response to E. coli O157:H7 infections.Role: PIU01 AI061187 Weigl (PI) 12/1/04-8/31/08NIH/NIAID – Program for Appropriate Technology in Health (PATH)Multi-plex, Point-of-care Test for Enteric PathogensThe major goal of this project is to design and test a point-of-care, nanotechnology-based, system for theidentification of enteric bacterial pathogens (Campylobacter, Escherichia coli O157:H7, Salmonella, andShigella).Role: PI on SubcontractP30 DK052574 Li (PI) 3/1/00-11/30/09NIH/NIDDKRegulatory Factors in the GI TractThe major goals of the project are to promote collaborative and synergistic interactions between individualinvestigators from multiple disciplines engaged in digestive-diseases related research, pool departmental anddivisional resources to provide and distribute services and expertise that may otherwise not be available toindividual investigators, in a cost-effective manner, provide funding support for investigators to initiate anddevelop new digestive diseases-related research initiatives that will subsequently be competitive for moreconventional mechanisms of funding, and to train medical and graduate students, housestaff, postdoctoralfellows, physician faculty, and allied health professionals in digestive diseases related research.Role: PI on SubcontractCompleted Research SupportR01 AI047499 Tarr (PI) 9/30/99-8/31/05NIH/NIAIDEvolution of Virulence by Gene AcquisitionAssess lineage-specific differences in gene expression, and assess virulence evolution by gene acquisition.Role: PITarr (PI) 7/1/99-6/30/05The Boeing CompanyImmunotherapy Targets in Inflammatory Bowel DiseaseThe major goals of this project are to test the hypothesis that there exist specific and identifiable differences inthe expression of an array of intestinal immune/inflammatory factors in the gastrointestinal mucosa of patientswith ulcerative colitis and Crohn’s Disease, compared to those found in the gastrointestinal mucosa of patientswithout these inflammatory bowel diseases. We are also testing the hypothesis that there exist specific andidentifiable differences in the expression of an array of intestinal immune/inflammatory factors in patients withulcerative colitis and Crohn’s Disease that are associated with the clinical course in the year after diagnosis.Role: PI2002-35212-14257 Tarr (PI) 9/1/03-3/14/07USDA/NRIDiarrhea Etiology and Risk Factors StudyDetermine the cause(s) of unexplained childhood diarrhea, and assess risk factors for acquiring reportableenteric infections.Role: PI