William A Petri

Education

  • MD, University of Virginia
  • Residency, University Hospital of Cleveland
  • Clinical Fellowship, University of Virginia
  • PhD, University of Virginia

Primary Appointment

  • Professor and Division Chief, Medicine- Infectious Diseases and International Health

Contact

Research Interest(s)

Immune mechanisms of defense against enteric (diarrheal) infections

Research Description

William A. Petri, Jr., M.D., Ph.D. studies immunology and molecular pathogenesis of enteric infections and their consequences. The scope of research includes molecular parasitology of Entamoeba, innate immune host defense against Clostridium difficile, and in Bangladesh acquired immunity to Cryptosporidium.

AMEBIASIS: Focusing on amebic colitis, his lab identified the Gal/GalNAc-binding lectin of the parasite Entamoeba histolytica that mediates contact-dependent killing of host cells. Cell biologic studies of adherence, apoptosis and endocytosis of human cells by the parasite are active areas of investigation. This work is supported by an R01 to Dr. Petri from the NIH. DNA transformation of the parasite was pioneered in the lab, and is used to study molecular pathogenesis. Clinically, the group has developed FDA-approved antigen-detection tests that allow sensitive and specific diagnosis of amebiasis. Current work is focused on the mechanism of Entamoeba killing of host cells by a unique process called trogocytosis (Ralston KD et al, Nature (2014) 508:526) and the development of an amebiasis vaccine in partnership with the Infectious Diseases Research Institute of Seattle (Abhyankar M et al. Vaccine 35 (2017) 916).

C. DIFFICILE: The innate immune response to Clostridium difficile colitis is a new area of investigation. Also supported by a separate R01 to Dr. Petri from the NIH, his lab has discovered that eosinophils protect from C. difficile in both mice (Buonomo EL et al., Cell Reports 2016, 16:1-12) and humans (Kulaylat AS et al., JAMA Surg. doi:10.1001/jamasurg.2018.3174.) Understanding how eosinophils protect, and why inflammasome activation by toxin activation of TLR2 causes death (Cowardin CA et al. Nature Microbiology 2016, doi:10.1038/nmicrobiol.2016.108) are current ares of focus.

CRYPTOSPORIDIOSIS: The acquired immune response to Cryptosporidium hominis in children growing up in the urban slums of Bangladesh is a third area of investigation. Supported by another NIH R01 grant, the focus of this research is the role of mucosal immunity in defense, including identification of parasite proteins recognized by IgA and by immune T cells (Steiner KL et al Clin Infect Dis. 2018 Apr 20. doi: 10.1093/cid/ciy310).

17 graduate students have received the PhD degree under Dr. Petri’s mentorship all of whom continue in science, and 17 postdoctoral fellows almost all of whom now have their own independent support from the NIH. Currently there are five graduate students three postdoctoral fellows and 6 faculty conducting research in the Petri group.

Selected Publications

  • Duggal P, Petri W. Does Malnutrition Have a Genetic Component? Annual review of genomics and human genetics. 2018;19 247-262. PMID: 29874104
  • Gilmartin A, Petri W. Exploring the mechanism of amebic trogocytosis: the role of amebic lysosomes. Microbial cell (Graz, Austria). 2018;5(1): 1-3. PMID: 29354646 | PMCID: PMC5772035
  • Jiang N, Cowan M, Moonah S, Petri W. The Impact of Systemic Inflammation on Neurodevelopment. Trends in molecular medicine. 2018;24(9): 794-804. PMID: 30006148 | PMCID: PMC6110951
  • Kabir M, Ahmed E, Hossain B, Alam M, Ahmed S, Taniuchi M, Gilchrist C, Houpt E, Faruque A, Petri W, Haque R. Giardia/Cryptosporidium QUIK CHEK® Assay is more Specific than qPCR for Rapid Point-of-care Diagnosis of Cryptosporidiosis in Infants in Bangladesh. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018. PMID: 29718129
  • Kulaylat A, Buonomo E, Scully K, Hollenbeak C, Cook H, Petri W, Stewart D. Development and Validation of a Prediction Model for Mortality and Adverse Outcomes Among Patients With Peripheral Eosinopenia on Admission for Clostridium difficile Infection. JAMA surgery. 2018. PMID: 30208386
  • Kulaylat A, Buonomo E, Scully K, Hollenbeak C, Cook H, Petri W, Stewart D. Development and Validation of a Prediction Model for Mortality and Adverse Outcomes Among Patients With Peripheral Eosinopenia on Admission for Clostridium difficile Infection. JAMA surgery. 2018. PMID: 30208386
  • Kumar M, Ji B, Babaei P, Das P, Lappa D, Ramakrishnan G, Fox T, Haque R, Petri W, Bäckhed F, Nielsen J. Gut microbiota dysbiosis is associated with malnutrition and reduced plasma amino acid levels: Lessons from genome-scale metabolic modeling. Metabolic engineering. 2018;49 128-142. PMID: 30075203
  • Mahfuz M, Alam M, Fahim S, Gazi M, Raihan M, Hossain M, Egner P, Bessong P, Petri W, Groopman J, Ahmed T. Aflatoxin exposure in children living in Mirpur, Dhaka: data from MAL-ED companion study. Journal of exposure science & environmental epidemiology. 2018. PMID: 30185944
  • Marie C, Ali A, Chandwe K, Petri W, Kelly P. Pathophysiology of environmental enteric dysfunction and its impact on oral vaccine efficacy. Mucosal immunology. 2018. PMID: 29988114
  • Richard S, McCormick B, Seidman J, Rasmussen Z, Kosek M, Rogawski E, Petri W, Bose A, Mduma E, Maciel B, Chandyo R, Bhutta Z, Turab A, Bessong P, Mahfuz M, Caulfield L. Relationships among Common Illness Symptoms and the Protective Effect of Breastfeeding in Early Childhood in MAL-ED: An Eight-Country Cohort Study. The American journal of tropical medicine and hygiene. 2018;98(3): 904-912. PMID: 29380724 | PMCID: PMC5930868
  • Rogawski E, Platts-Mills J, Colgate E, Haque R, Zaman K, Petri W, Kirkpatrick B. Quantifying the Impact of Natural Immunity on Rotavirus Vaccine Efficacy Estimates: A Clinical Trial in Dhaka, Bangladesh (PROVIDE) and a Simulation Study. The Journal of infectious diseases. 2018;217(6): 861-868. PMID: 29514306 | PMCID: PMC5853827
  • Schnee A, Haque R, Taniuchi M, Uddin J, Alam M, Liu J, Rogawski E, Kirkpatrick B, Houpt E, Petri W, Platts-Mills J. Identification of etiology-specific diarrhea associated with linear growth faltering in Bangladeshi infants. American journal of epidemiology. 2018. PMID: 29767678
  • Schnee A, Haque R, Taniuchi M, Uddin M, Petri W. Evaluation of Two New Membrane-Based and Microtiter Plate Enzyme-Linked Immunosorbent Assays for Detection of Campylobacter jejuni in Stools of Bangladeshi Children. Journal of clinical microbiology. 2018;56(9). PMID: 29925645 | PMCID: PMC6113481
  • Troeger C, Colombara D, Rao P, Khalil I, Brown A, Brewer T, Guerrant R, Houpt E, Kotloff K, Misra K, Petri W, Platts-Mills J, Riddle M, Swartz S, Forouzanfar M, Reiner R, Hay S, Mokdad A. Global disability-adjusted life-year estimates of long-term health burden and undernutrition attributable to diarrhoeal diseases in children younger than 5 years. The Lancet. Global health. 2018;6(3): e255-e269. PMID: 29433665 | PMCID: PMC5861379
  • Watanabe K, Petri W. Learning from the research on amebiasis and gut microbiome: Is stimulation by gut flora essential for effective neutrophil mediated protection from external pathogens? Gut microbes. 2018; 1-5. PMID: 30252579
  • Abhyankar M, Noor Z, Tomai M, Elvecrog J, Fox C, Petri W. Nanoformulation of synergistic TLR ligands to enhance vaccination against Entamoeba histolytica. Vaccine. 2017;35(6): 916-922. PMID: 28089548 | PMCID: PMC5301946
  • Ali A, Zaman U, Mahmud S, Zahid G, Kazi M, Petri W, Bhutta Z, Zaidi A, Hughes M. Impact of maternal respiratory infections on low birth weight - a community based longitudinal study in an urban setting in Pakistan. BMC pregnancy and childbirth. 2017;17(1): 111. PMID: 28399895 | PMCID: PMC5387226
  • Burgess S, Gilchrist C, Lynn T, Petri W. Parasitic Protozoa and Interactions with the Host Intestinal Microbiota. Infection and immunity. 2017;85(8). PMID: 28584161 | PMCID: PMC5520446
  • Gilmartin A, Ralston K, Petri W. Inhibition of Amebic Lysosomal Acidification Blocks Amebic Trogocytosis and Cell Killing. mBio. 2017;8(4). PMID: 28851845 | PMCID: PMC5574710
  • Jiang N, Tofail F, Ma J, Haque R, Kirkpatrick B, Nelson C, Petri W. Early Life Inflammation and Neurodevelopmental Outcome in Bangladeshi Infants Growing Up in Adversity. The American journal of tropical medicine and hygiene. 2017;97(3): 974-979. PMID: 28722635 | PMCID: PMC5590603
  • Lu M, Zhou J, Naylor C, Kirkpatrick B, Haque R, Petri W, Ma J. Application of penalized linear regression methods to the selection of environmental enteropathy biomarkers. Biomarker research. 2017;5 9. PMID: 28293424 | PMCID: PMC5345248
  • Ngobeni R, Samie A, Moonah S, Watanabe K, Petri W, Gilchrist C. Entamoeba Species in South Africa: Correlations With the Host Microbiome, Parasite Burdens, and First Description of Entamoeba bangladeshi Outside of Asia. The Journal of infectious diseases. 2017. PMID: 29236996 | PMCID: PMC5853652
  • Noor Z, Watanabe K, Abhyankar M, Burgess S, Buonomo E, Cowardin C, Petri W. Role of Eosinophils and Tumor Necrosis Factor Alpha in Interleukin-25-Mediated Protection from Amebic Colitis. mBio. 2017;8(1). PMID: 28246365 | PMCID: PMC5347349
  • Platts-Mills J, Taniuchi M, Uddin M, Sobuz S, Mahfuz M, Gaffar S, Mondal D, Hossain M, Islam M, Ahmed A, Petri W, Haque R, Houpt E, Ahmed T. Association between enteropathogens and malnutrition in children aged 6-23 mo in Bangladesh: a case-control study. The American journal of clinical nutrition. 2017;105(5): 1132-1138. PMID: 28381477 | PMCID: PMC5402031
  • Ramakrishnan G, Petri W. Secondary Carnitine Deficiency in Environmental Enteric Dysfunction. EBioMedicine. 2017;17 9-10. PMID: 28254256 | PMCID: PMC5360577
  • Schnee A, Petri W. Campylobacter jejuni and associated immune mechanisms: short-term effects and long-term implications for infants in low-income countries. Current opinion in infectious diseases. 2017;30(3): 322-328. PMID: 28157786 | PMCID: PMC5560167
  • Upfill-Brown A, Taniuchi M, Platts-Mills J, Kirkpatrick B, Burgess S, Oberste M, Weldon W, Houpt E, Haque R, Zaman K, Petri W. Non-Specific Effects of Oral Polio Vaccine on Diarrheal Burden and Etiology among Bangladeshi Infants. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2017. PMID: 28444240 | PMCID: PMC5848225
  • Zhang Y, Zhou J, Niu F, Donowitz J, Haque R, Petri W, Ma J. Characterizing early child growth patterns of height-for-age in an urban slum cohort of Bangladesh with functional principal component analysis. BMC pediatrics. 2017;17(1): 84. PMID: 28327104 | PMCID: PMC5359797
  • Burgess S, Petri W. The Intestinal Bacterial Microbiome and E. histolytica Infection. Current tropical medicine reports. 2016;3 71-74. PMID: 27525214 | PMCID: PMC4967426
  • Burgess S, Saleh M, Cowardin C, Buonomo E, Noor Z, Watanabe K, Abhyankar M, Lajoie S, Wills-Karp M, Petri W. Role of Serum Amyloid A, Granulocyte-Macrophage Colony-Stimulating Factor, and Bone Marrow Granulocyte-Monocyte Precursor Expansion in Segmented Filamentous Bacterium-Mediated Protection from Entamoeba histolytica. Infection and immunity. 2016;84(10): 2824-32. PMID: 27456830 | PMCID: PMC5038085
  • Cowardin C, Buonomo E, Saleh M, Wilson M, Burgess S, Kuehne S, Schwan C, Eichhoff A, Koch-Nolte F, Lyras D, Aktories K, Minton N, Petri W. The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia. Nature microbiology. 2016;1(8): 16108. PMID: 27573114 | PMCID: PMC5010011
  • Fleece M, Heptinstall J, Khan S, Kabir M, Herbein J, Haque R, Petri W. Evaluation of a Rapid Lateral Flow Point-of-Care Test for Detection of Cryptosporidium. The American journal of tropical medicine and hygiene. 2016;95(4): 840-841. PMID: 27573629 | PMCID: PMC5062784
  • Guerrant R, Leite A, Pinkerton R, Medeiros P, Cavalcante P, DeBoer M, Kosek M, Duggan C, Gewirtz A, Kagan J, Gauthier A, Swann J, Mayneris-Perxachs J, Bolick D, Maier E, Guedes M, Moore S, Petri W, Havt A, Lima I, Prata M, Michaleckyj J, Scharf R, Sturgeon C, Fasano A, Lima A. Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil. PloS one. 2016;11(9): e0158772. PMID: 27690129 | PMCID: PMC5045163
  • Hossain M, Haque R, Mondal D, Mahfuz M, Ahmed A, Islam M, Guerrant R, Petri W, Ahmed T. Undernutrition, Vitamin A and Iron Deficiency Are Associated with Impaired Intestinal Mucosal Permeability in Young Bangladeshi Children Assessed by Lactulose/Mannitol Test. PloS one. 2016;11(12): e0164447. PMID: 27906964 | PMCID: PMC5132308
  • Ramakrishnan G, Wright M, Alam M, Naylor C, Kabir M, Zerin A, Ferdous T, Pedersen K, Hennig B, Donowitz J, Wegmuller R, Haque R, Petri W, Herbein J, Gilchrist C. Rapid assessment of tetanus vaccine-induced immunity in Bangladesh and the Gambia. Diagnostic microbiology and infectious disease. 2016. PMID: 27916543 | PMCID: PMC5292284
  • Steele S, Melchor S, Petri W. Tuft Cells: New Players in Colitis. Trends in molecular medicine. 2016;22(11): 921-924. PMID: 27717671 | PMCID: PMC5159242
  • Verkerke H, Sobuz S, Ma J, Petri S, Reichman D, Qadri F, Rahman M, Haque R, Petri W. Malnutrition Is Associated with Protection from Rotavirus Diarrhea: Evidence from a Longitudinal Birth Cohort Study in Bangladesh. Journal of clinical microbiology. 2016;54(10): 2568-74. PMID: 27510830 | PMCID: PMC5035411
  • Watanabe K, Petri W. Environmental Enteropathy: Elusive but Significant Subclinical Abnormalities in Developing Countries. EBioMedicine. 2016;10 25-32. PMID: 27495791 | PMCID: PMC5006727
  • Buonomo E, Petri W. The Bug Stops Here: Innate Lymphoid Cells in Clostridium difficile Infection. Cell host & microbe. 2015;18(1): 5-6. PMID: 26159713
  • Cowardin C, Kuehne S, Buonomo E, Marie C, Minton N, Petri W. Inflammasome activation contributes to interleukin-23 production in response to Clostridium difficile. mBio. 2015;6(1). PMID: 25626905 | PMCID: PMC4324312
  • Gilchrist C, Turner S, Riley M, Petri W, Hewlett E. Whole-genome sequencing in outbreak analysis. Clinical microbiology reviews. 2015;28(3): 541-63. PMID: 25876885 | PMCID: PMC4399107
  • Gilmartin A, Petri W. Exploring the role of environmental enteropathy in malnutrition, infant development and oral vaccine response. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 2015;370(1671). PMID: 25964455 | PMCID: PMC4527388
  • Kirkpatrick B, Colgate E, Mychaleckyj J, Haque R, Dickson D, Carmolli M, Nayak U, Taniuchi M, Naylor C, Qadri F, Ma J, Alam M, Walsh M, Diehl S, Petri W. The "Performance of Rotavirus and Oral Polio Vaccines in Developing Countries" (PROVIDE) study: description of methods of an interventional study designed to explore complex biologic problems. The American journal of tropical medicine and hygiene. 2015;92(4): 744-51. PMID: 25711607 | PMCID: PMC4385767
  • Madan R, Petri W. Role of obesity and adipose tissue-derived cytokine leptin during Clostridium difficile infection. Anaerobe. 2015;34 182-6. PMID: 25638400 | PMCID: PMC4492854
  • Marie C, Verkerke H, Theodorescu D, Petri W. A whole-genome RNAi screen uncovers a novel role for human potassium channels in cell killing by the parasite Entamoeba histolytica. Scientific reports. 2015;5 13613. PMID: 26346926 | PMCID: PMC4561901
  • Petri W, Naylor C, Haque R. Environmental enteropathy and malnutrition: do we know enough to intervene? BMC medicine. 2015;12 187. PMID: 25604120 | PMCID: PMC4197320
  • Ramakrishnan G, Pedersen K, Guenette D, Sink J, Haque R, Petri W, Herbein J, Gilchrist C. Utility of recombinant fragment C for assessment of anti-tetanus antibodies in plasma. Diagnostic microbiology and infectious disease. 2015. PMID: 25749462
  • Watanabe K, Petri W. Molecular biology research to benefit patients with Entamoeba histolytica infection. Molecular microbiology. 2015. PMID: 26173474
  • Ahmed T, Mahfuz M, Islam M, Mondal D, Hossain M, Ahmed A, Tofail F, Gaffar S, Haque R, Guerrant R, Petri W. The MAL-ED cohort study in Mirpur, Bangladesh. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2014;59 S280-6. PMID: 25305298
  • Burgess S, Buonomo E, Carey M, Cowardin C, Naylor C, Noor Z, Wills-Karp M, Petri W. Bone marrow dendritic cells from mice with an altered microbiota provide interleukin 17A-dependent protection against Entamoeba histolytica colitis. mBio. 2014;5(6): e01817. PMID: 25370489 | PMCID: PMC4222101
  • Checkley W, White A, Jaganath D, Arrowood M, Chalmers R, Chen X, Fayer R, Griffiths J, Guerrant R, Hedstrom L, Huston C, Kotloff K, Kang G, Mead J, Miller M, Petri W, Priest J, Roos D, Striepen B, Thompson R, Ward H, Van Voorhis W, Xiao L, Zhu G, Houpt E. A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium. The Lancet. Infectious diseases. 2014;15(1): 85-94. PMID: 25278220 | PMCID: PMC4401121
  • Cowardin C, Petri W. Host recognition of Clostridium difficile and the innate immune response. Anaerobe. 2014;30 205-9. PMID: 25223264 | PMCID: PMC4258135
  • Donowitz J, Petri W. Pediatric small intestine bacterial overgrowth in low-income countries. Trends in molecular medicine. 2014;21(1): 6-15. PMID: 25486880
  • Gurley E, Salje H, Homaira N, Ram P, Haque R, Petri W, Bresee J, Moss W, Luby S, Breysse P, Azziz-Baumgartner E. Indoor exposure to particulate matter and age at first acute lower respiratory infection in a low-income urban community in bangladesh. American journal of epidemiology. 2014;179(8): 967-73. PMID: 24607596
  • Hsiao A, Ahmed A, Subramanian S, Griffin N, Drewry L, Petri W, Haque R, Ahmed T, Gordon J. Members of the human gut microbiota involved in recovery from Vibrio cholerae infection. Nature. 2014;515(7527): 423-6. PMID: 25231861
  • Jiang N, Tofail F, Moonah S, Scharf R, Taniuchi M, Ma J, Hamadani J, Gurley E, Houpt E, Azziz-Baumgartner E, Haque R, Petri W. Febrile illness and pro-inflammatory cytokines are associated with lower neurodevelopmental scores in Bangladeshi infants living in poverty. BMC pediatrics. 2014;14 50. PMID: 24548288 | PMCID: PMC3936797
  • Kosek M, Guerrant R, Kang G, Bhutta Z, Yori P, Gratz J, Gottlieb M, Lang D, Lee G, Haque R, Mason C, Ahmed T, Lima A, Petri W, Houpt E, Olortegui M, Seidman J, Mduma E, Samie A, Babji S. Assessment of environmental enteropathy in the MAL-ED cohort study: theoretical and analytic framework. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2014;59 S239-47. PMID: 25305293 | PMCID: PMC4204611
  • Linford A, Jiang N, Edwards T, Sherman N, Van Voorhis W, Stewart L, Myler P, Staker B, Petri W. Crystal structure and putative substrate identification for the Entamoeba histolytica low molecular weight tyrosine phosphatase. Molecular and biochemical parasitology. 2014. PMID: 24548880 | PMCID: PMC4022148
  • Liu J, Lurain K, Sobuz S, Begum S, Kumburu H, Gratz J, Kibiki G, Toney D, Gautam R, Bowen M, Petri W, Haque R, Houpt E. Molecular genotyping and quantitation assay for rotavirus surveillance. Journal of virological methods. 2014;213 157-163. PMID: 25526999
  • Marie C, Petri W. Regulation of virulence of Entamoeba histolytica. Annual review of microbiology. 2014;68 493-520. PMID: 25002094
  • Moonah S, Abhyankar M, Haque R, Petri W. The macrophage migration inhibitory factor homolog of Entamoeba histolytica binds to and immunomodulates host macrophages. Infection and immunity. 2014;82(9): 3523-30. PMID: 24818664 | PMCID: PMC4187827
  • Moss D, Priest J, Hamlin K, Derado G, Herbein J, Petri W, Lammie P. Longitudinal evaluation of enteric protozoa in haitian children by stool exam and multiplex serologic assay. The American journal of tropical medicine and hygiene. 2014;90(4): 653-60. PMID: 24591430
  • Naylor C, Burgess S, Madan R, Buonomo E, Razzaq K, Ralston K, Petri W. Leptin Receptor Mutation Results in Defective Neutrophil Recruitment to the Colon during Entamoeba histolytica Infection. mBio. 2014;5(6). PMID: 25516614 | PMCID: PMC4271549
  • Ralston K, Solga M, Mackey-Lawrence N, Bhattacharya A, Petri W. Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion. Nature. 2014. PMID: 24717428
  • Subramanian S, Huq S, Yatsunenko T, Haque R, Mahfuz M, Alam M, Benezra A, DeStefano J, Meier M, Muegge B, Barratt M, VanArendonk L, Zhang Q, Province M, Petri W, Ahmed T, Gordon J. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature. 2014;510(7505): 417-21. PMID: 24896187 | PMCID: PMC4189846
  • Taniuchi M, Begum S, Uddin M, Platts-Mills J, Liu J, Kirkpatrick B, Chowdhury A, Jamil K, Haque R, Petri W, Houpt E. Kinetics of Poliovirus Shedding following Oral Vaccination as Measured by Quantitative Reverse Transcription-PCR versus Culture. Journal of clinical microbiology. 2014;53(1): 206-11. PMID: 25378579 | PMCID: PMC4290924
  • Verkerke H, Hanbury B, Siddique A, Samie A, Haque R, Herbein J, Petri W. Multi-site clinical evaluation of a rapid test for Entamoeba histolytica in stool. Journal of clinical microbiology. 2014. PMID: 25428152
  • Verkerke H, Naylor C, Zabeau L, Tavernier J, Petri W, Marie C. Kinetics of leptin binding to the Q223R leptin receptor. PloS one. 2014;9(4): e94843. PMID: 24743494 | PMCID: PMC3990580
  • Verkerke H, Sobuz S, Petri W. Molecular diagnosis of infectious diarrhea: focus on enteric protozoa. Expert review of molecular diagnostics. 2014;14(8): 935-46. PMID: 25139776