Dana Borden Lacy, Ph.D.



Visit Lab Site

Faculty Appointments
Professor of Pathology, Microbiology and Immunology Professor of BiochemistryEdward and Nancy Fody Chair in Pathology
Ph.D., Chemistry, University of California, Berkeley, CaliforniaB.S., Chemistry, University of North Carolina, Chapel Hill, North Carolina
Office Address
A4116A MCN
Nashville, TN 37232
Research Description
Pathogenic bacteria have evolved a diverse array of mechanisms for delivering toxins and other virulence factors into the interior of host cells. Studying the molecular structures of these virulence factors alone and in complex with host receptors, membranes, and inhibitors can lend insight into how these delivery processes occur and how these processes can be exploited or prevented. Current research in the Lacy laboratory is primarily focused on the structure and function of large clostridial cytotoxins, including the two toxins responsible for symptoms in Clostridioides difficile infection. Structural biology is combined with cellular and animal models of intoxication and infection to understand the toxin-host interaction at the molecular level. In addition, we aim to identify new targets for and strategies for vaccine design.
Research Keywords
Clostridioides difficile, bacteriology, toxins, pathogenesis, epithelial cells, X-ray crystallography, electron microscopy, structural biology, microbiology, cryo-EM, reproductive health, Paeniclostridium sordellii, vaccines, therapeutics, antibodies, biochemistry, host pathogen interaction, immunology
Soto Ocaña J, Bayard NU, Hart JL, Thomas AK, Furth EE, Lacy DB, Aronoff DM, Zackular JP. Nonsteroidal anti-inflammatory drugs sensitize epithelial cells to Clostridioides difficile toxin-mediated mitochondrial damage. Sci Adv [print-electronic]. 2023 Jul 7/21/2023; 9(29): eadh5552. PMID: 37467340, PMCID: PMC10355836, DOI: 10.1126/sciadv.adh5552, ISSN: 2375-2548.

Peritore-Galve FC, Kaji I, Smith A, Walker LM, Shupe JA, Washington MK, Algood HMS, Dudeja PK, Goldenring JR, Lacy DB. Increased intestinal permeability and downregulation of absorptive ion transporters Nhe3, Dra, and Sglt1 contribute to diarrhea during Clostridioides difficile infection. Gut Microbes. 2023; 15(1): 2225841. PMID: 37350393, PMCID: PMC10291935, DOI: 10.1080/19490976.2023.2225841, ISSN: 1949-0984.

Lunnemann HM, Shealy NG, Reyzer ML, Shupe JA, Green EH, Siddiqi U, Lacy DB, Byndloss MX, Markham NO. Cecum axis (CecAx) preservation reveals physiological and pathological gradients in mouse gastrointestinal epithelium. Gut Microbes. 2023; 15(1): 2185029. PMID: 36872510, PMCID: PMC10012889, DOI: 10.1080/19490976.2023.2185029, ISSN: 1949-0984.

Castro-Córdova P, Otto-Medina M, Montes-Bravo N, Brito-Silva C, Lacy DB, Paredes-Sabja D. Redistribution of the Novel Clostridioides difficile Spore Adherence Receptor E-Cadherin by TcdA and TcdB Increases Spore Binding to Adherens Junctions. Infect Immun [print-electronic]. 2022 Nov 11/30/2022; e0047622. PMID: 36448839, DOI: 10.1128/iai.00476-22, ISSN: 1098-5522.

Bernard SC, Washington MK, Lacy DB. Paeniclostridium sordellii uterine infection is dependent on the estrous cycle. PLoS Pathog. 2022 Nov; 18(11): e1010997. PMID: 36409774, PMCID: PMC9721474, PII: PPATHOGENS-D-22-01162, DOI: 10.1371/journal.ppat.1010997, ISSN: 1553-7374.

Sheedlo MJ, Ohi MD, Lacy DB, Cover TL. Molecular architecture of bacterial type IV secretion systems. PLoS Pathog. 2022 Aug; 18(8): e1010720. PMID: 35951533, PMCID: PMC9371333, PII: PPATHOGENS-D-22-00329, DOI: 10.1371/journal.ppat.1010720, ISSN: 1553-7374.

Saund K, Pirani A, Lacy DB, Hanna PC, Snitkin E. Strain Variation in Clostridioides difficile Cytotoxicity Associated with Genomic Variation at Both Pathogenic and Nonpathogenic Loci. MSphere [print-electronic]. 2022 Jun 6/29/2022; 7(3): e0017422. PMID: 35766503, PMCID: PMC9241522, DOI: 10.1128/msphere.00174-22, ISSN: 2379-5042.

Varley CD, Rogers LM, Dixon BR, Bernard SC, Lacy DB, Sulpizio E, Aronoff DM, Townes JM. Persistent bacteremia and psoas abscess caused by a lethal toxin-deficient Paeniclostridiumsordellii. Anaerobe [print-electronic]. 2022 Jun; 75: 102520. PMID: 35085782, PMCID: PMC9197960, PII: S1075-9964(22)00008-7, DOI: 10.1016/j.anaerobe.2022.102520, ISSN: 1095-8274.

Kordus SL, Thomas AK, Lacy DB. Clostridioides difficile toxins: mechanisms of action and antitoxin therapeutics. Nat Rev Microbiol [print-electronic]. 2022 May; 20(5): 285-98. PMID: 34837014, PMCID: PMC9018519, PII: 10.1038/s41579-021-00660-2, DOI: 10.1038/s41579-021-00660-2, ISSN: 1740-1534.

Peritore-Galve FC, Shupe JA, Cave RJ, Childress KO, Washington MK, Kuehne SA, Lacy DB. Glucosyltransferase-dependent and independent effects of Clostridioides difficile toxins during infection. PLoS Pathog. 2022 Feb; 18(2): e1010323. PMID: 35176123, PMCID: PMC8890742, PII: PPATHOGENS-D-21-02033, DOI: 10.1371/journal.ppat.1010323, ISSN: 1553-7374.

Caso GC, McClain MS, Erwin AL, Truelock MD, Campbell AM, Leasure CS, Nagel M, Schey KL, Lacy DB, Ohi MD, Cover TL. Functional Properties of Oligomeric and Monomeric Forms of Helicobacter pylori VacA Toxin. Infect Immun [print-electronic]. 2021 Nov 11/16/2021; 89(12): e0034821. PMID: 34543122, PMCID: PMC8594603, DOI: 10.1128/IAI.00348-21, ISSN: 1098-5522.

Sheedlo MJ, Durie CL, Chung JM, Chang L, Roberts J, Swanson M, Lacy DB, Ohi MD. Cryo-EM reveals new species-specific proteins and symmetry elements in the Legionella pneumophila Dot/Icm T4SS. Elife. 2021 Sep 9/14/2021; 10: PMID: 34519271, PMCID: PMC8486379, PII: 70427, DOI: 10.7554/eLife.70427, ISSN: 2050-084X.

Wexler AG, Guiberson ER, Beavers WN, Shupe JA, Washington MK, Lacy DB, Caprioli RM, Spraggins JM, Skaar EP. Clostridioides difficile infection induces a rapid influx of bile acids into the gut during colonization of the host. Cell Rep. 2021 Sep 9/7/2021; 36(10): 109683. PMID: 34496241, PMCID: PMC8445666, PII: S2211-1247(21)01130-X, DOI: 10.1016/j.celrep.2021.109683, ISSN: 2211-1247.

Monaghan TM, Seekatz AM, Markham NO, Yau TO, Hatziapostolou M, Jilani T, Christodoulou N, Roach B, Birli E, Pomenya O, Louie T, Lacy DB, Kim P, Lee C, Kao D, Polytarchou C. Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection Associates With Functional Alterations in Circulating microRNAs. Gastroenterology [print-electronic]. 2021 Jul; 161(1): 255-270.e4. PMID: 33844988, PMCID: PMC8579492, PII: S0016-5085(21)00577-1, DOI: 10.1053/j.gastro.2021.03.050, ISSN: 1528-0012.

Markham NO, Bloch SC, Shupe JA, Laubacher EN, Thomas AK, Kroh HK, Childress KO, Peritore-Galve FC, Washington MK, Coffey RJ, Lacy DB. Murine Intrarectal Instillation of Purified Recombinant Clostridioides difficile Toxins Enables Mechanistic Studies of Pathogenesis. Infect Immun [electronic-print]. 2021 Mar 3/17/2021; 89(4): PMID: 33468584, PMCID: PMC8090962, PII: IAI.00543-20, DOI: 10.1128/IAI.00543-20, ISSN: 1098-5522.

Parnell JM, Fazili I, Bloch SC, Lacy DB, Garcia-Lopez VA, Bernard R, Skaar EP, Edwards KM, Nicholson MR. Two-step Testing for Clostridioides Difficile is Inadequate in Differentiating Infection From Colonization in Children. J Pediatr Gastroenterol Nutr. 2021 Mar 3/1/2021; 72(3): 378-83. PMID: 32925555, PMCID: PMC7870537, PII: 00005176-202103000-00008, DOI: 10.1097/MPG.0000000000002944, ISSN: 1536-4801.

Janezic S, Dingle K, Alvin J, Accetto T, Didelot X, Crook DW, Lacy DB, Rupnik M. Comparative genomics of Clostridioides difficile toxinotypes identifies module-based toxin gene evolution. Microb Genom. 2020 Oct; 6(10): PMID: 33030421, PMCID: PMC7660249, DOI: 10.1099/mgen.0.000449, ISSN: 2057-5858.

Sheedlo MJ, Chung JM, Sawhney N, Durie CL, Cover TL, Ohi MD, Lacy DB. Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex. Elife. 2020 Sep 9/2/2020; 9: PMID: 32876048, PMCID: PMC7511236, PII: 59495, DOI: 10.7554/eLife.59495, ISSN: 2050-084X.

Durie CL, Sheedlo MJ, Chung JM, Byrne BG, Su M, Knight T, Swanson M, Lacy DB, Ohi MD. Structural analysis of the Legionella pneumophila Dot/Icm type IV secretion system core complex. Elife. 2020 Sep 9/2/2020; 9: PMID: 32876045, PMCID: PMC7511231, PII: 59530, DOI: 10.7554/eLife.59530, ISSN: 2050-084X.

Cover TL, Lacy DB, Ohi MD. The Helicobacter pylori Cag Type IV Secretion System. Trends Microbiol [print-electronic]. 2020 Aug; 28(8): 682-95. PMID: 32451226, PMCID: PMC7363556, PII: S0966-842X(20)30040-8, DOI: 10.1016/j.tim.2020.02.004, ISSN: 1878-4380.

Farrow MA, Chumber NM, Bloch SC, King M, Moton-Melancon K, Shupe J, Washington MK, Spiller BW, Lacy DB. Small Molecule Inhibitor Screen Reveals Calcium Channel Signaling as a Mechanistic Mediator of Clostridium difficile TcdB-Induced Necrosis. ACS Chem Biol [print-electronic]. 2020 May 5/15/2020; 15(5): 1212-21. PMID: 31909964, PMCID: PMC7230009, DOI: 10.1021/acschembio.9b00906, ISSN: 1554-8937.

Mileto SJ, Jardé T, Childress KO, Jensen JL, Rogers AP, Kerr G, Hutton ML, Sheedlo MJ, Bloch SC, Shupe JA, Horvay K, Flores T, Engel R, Wilkins S, McMurrick PJ, Lacy DB, Abud HE, Lyras D. Clostridioides difficile infection damages colonic stem cells via TcdB, impairing epithelial repair and recovery from disease. Proc Natl Acad Sci U S A [print-electronic]. 2020 Apr 4/7/2020; 117(14): 8064-73. PMID: 32198200, PMCID: PMC7149309, PII: 1915255117, DOI: 10.1073/pnas.1915255117, ISSN: 1091-6490.

Tam J, Icho S, Utama E, Orrell KE, Gómez-Biagi RF, Theriot CM, Kroh HK, Rutherford SA, Lacy DB, Melnyk RA. Intestinal bile acids directly modulate the structure and function of C. difficile TcdB toxin. Proc Natl Acad Sci U S A [print-electronic]. 2020 Mar 3/24/2020; 117(12): 6792-800. PMID: 32152097, PMCID: PMC7104382, PII: 1916965117, DOI: 10.1073/pnas.1916965117, ISSN: 1091-6490.

Sheedlo MJ, Anderson DM, Thomas AK, Lacy DB. Structural elucidation of the Clostridioides difficile transferase toxin reveals a single-site binding mode for the enzyme. Proc Natl Acad Sci U S A [print-electronic]. 2020 Mar 3/17/2020; 117(11): 6139-44. PMID: 32123082, PMCID: PMC7084131, PII: 1920555117, DOI: 10.1073/pnas.1920555117, ISSN: 1091-6490.

Anderson DM, Sheedlo MJ, Jensen JL, Lacy DB. Structural insights into the transition of Clostridioides difficile binary toxin from prepore to pore. Nat Microbiol [print-electronic]. 2020 Jan; 5(1): 102-7. PMID: 31712627, PMCID: PMC6925320, PII: 10.1038/s41564-019-0601-8, DOI: 10.1038/s41564-019-0601-8, ISSN: 2058-5276.

Chung JM, Sheedlo MJ, Campbell AM, Sawhney N, Frick-Cheng AE, Lacy DB, Cover TL, Ohi MD. Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 2019 Jun 6/18/2019; 8: PMID: 31210639, PMCID: PMC6620104, PII: 47644, DOI: 10.7554/eLife.47644, ISSN: 2050-084X.

Palmer LD, Jordan AT, Maloney KN, Farrow MA, Gutierrez DB, Gant-Branum R, Burns WJ, Romer CE, Tsui T, Allen JL, Beavers WN, Nei YW, Sherrod SD, Lacy DB, Norris JL, McLean JA, Caprioli RM, Skaar EP. Zinc intoxication induces ferroptosis in A549 human lung cells. Metallomics. 2019 May 5/22/2019; 11(5): 982-93. PMID: 30968088, PMCID: PMC6531343, DOI: 10.1039/c8mt00360b, ISSN: 1756-591X.

Su M, Erwin AL, Campbell AM, Pyburn TM, Salay LE, Hanks JL, Lacy DB, Akey DL, Cover TL, Ohi MD. Cryo-EM Analysis Reveals Structural Basis of Helicobacter pylori VacA Toxin Oligomerization. J Mol Biol [print-electronic]. 2019 May 5/3/2019; 431(10): 1956-65. PMID: 30954575, PMCID: PMC6625667, PII: S0022-2836(19)30179-2, DOI: 10.1016/j.jmb.2019.03.029, ISSN: 1089-8638.

Yang S, Harding AT, Sweeney C, Miao D, Swan G, Zhou C, Jiang Z, Fitzgerald KA, Hammer G, Bergo MO, Kroh HK, Lacy DB, Sun C, Glogauer M, Que LG, Heaton NS, Wang D. Control of antiviral innate immune response by protein geranylgeranylation. Sci Adv. 2019 May; 5(5): eaav7999. PMID: 31149635, PMCID: PMC6541464, PII: aav7999, DOI: 10.1126/sciadv.aav7999, ISSN: 2375-2548.

Kroh HK, Chandrasekaran R, Zhang Z, Rosenthal K, Woods R, Jin X, Nyborg AC, Rainey GJ, Warrener P, Melnyk RA, Spiller BW, Lacy DB. A neutralizing antibody that blocks delivery of the enzymatic cargo of Clostridium difficile toxin TcdB into host cells. J. Biol. Chem [print-electronic]. 2017 Nov 11/27/2017; PMID: 29180448, PII: M117.813428, DOI: 10.1074/jbc.M117.813428, ISSN: 1083-351X.

Chandrasekaran R, Lacy DB. The role of toxins in Clostridium difficile infection. FEMS Microbiol. Rev. 2017 Nov 11/1/2017; 41(6): 723-50. PMID: 29048477, PII: 4557158, DOI: 10.1093/femsre/fux048, ISSN: 1574-6976.

Gupta P, Zhang Z, Sugiman-Marangos SN, Tam J, Raman S, Julien JP, Kroh HK, Lacy DB, Murgolo N, Bekkari K, Therien AG, Hernandez LD, Melnyk RA. Functional defects in Clostridium difficile TcdB toxin uptake identify CSPG4 receptor binding determinants. J. Biol. Chem [print-electronic]. 2017 Aug 8/23/2017; PMID: 28842504, PII: M117.806687, DOI: 10.1074/jbc.M117.806687, ISSN: 1083-351X.

Surdel MC, Horvath DJ, Lojek LJ, Fullen AR, Simpson J, Dutter BF, Salleng KJ, Ford JB, Jenkins JL, Nagarajan R, Teixeira PL, Albertolle M, Georgiev IS, Jansen ED, Sulikowski GA, Lacy DB, Dailey HA, Skaar EP. Antibacterial photosensitization through activation of coproporphyrinogen oxidase. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2017 Aug 8/8/2017; 114(32): E6652-E6659. PMID: 28739897, PII: 1700469114, DOI: 10.1073/pnas.1700469114, ISSN: 1091-6490.

Kroh HK, Chandrasekaran R, Rosenthal K, Woods R, Jin X, Ohi MD, Nyborg AC, Rainey GJ, Warrener P, Spiller BW, Lacy DB. Use of a neutralizing antibody helps identify structural features critical for binding of Clostridium difficile toxin TcdA to the host cell surface. J. Biol. Chem [print-electronic]. 2017 Jul 7/13/2017; PMID: 28705932, PII: M117.781112, DOI: 10.1074/jbc.M117.781112, ISSN: 1083-351X.

Alvin JW, Lacy DB. Clostridium difficile toxin glucosyltransferase domains in complex with a non-hydrolyzable UDP-glucose analogue. J. Struct. Biol [print-electronic]. 2017 Jun; 198(3): 203-9. PMID: 28433497, PMCID: PMC5534367, PII: S1047-8477(17)30059-X, DOI: 10.1016/j.jsb.2017.04.006, ISSN: 1095-8657.

Norris JL, Farrow MA, Gutierrez DB, Palmer LD, Muszynski N, Sherrod SD, Pino JC, Allen JL, Spraggins JM, Lubbock AL, Jordan A, Burns W, Poland JC, Romer C, Manier ML, Nei YW, Prentice BM, Rose KL, Hill S, Van de Plas R, Tsui T, Braman NM, Keller MR, Rutherford SA, Lobdell N, Lopez CF, Lacy DB, McLean JA, Wikswo JP, Skaar EP, Caprioli RM. Integrated, High-Throughput, Multiomics Platform Enables Data-Driven Construction of Cellular Responses and Reveals Global Drug Mechanisms of Action. J. Proteome Res [print-electronic]. 2017 Mar 3/3/2017; 16(3): 1364-75. PMID: 28088864, DOI: 10.1021/acs.jproteome.6b01004, ISSN: 1535-3907.

Hernandez LD, Kroh HK, Hsieh E, Yang X, Beaumont M, Sheth PR, DiNunzio E, Rutherford SA, Ohi MD, Ermakov G, Xiao L, Secore S, Karczewski J, Racine F, Mayhood T, Fischer P, Sher X, Gupta P, Lacy DB, Therien AG. Epitopes and Mechanism of Action of the Clostridium difficile Toxin A-Neutralizing Antibody Actoxumab. J. Mol. Biol [print-electronic]. 2017 Feb 2/21/2017; PMID: 28232034, PII: S0022-2836(17)30085-2, DOI: 10.1016/j.jmb.2017.02.010, ISSN: 1089-8638.

Chandrasekaran R, Kenworthy AK, Lacy DB. Clostridium difficile Toxin A Undergoes Clathrin-Independent, PACSIN2-Dependent Endocytosis. PLoS Pathog. 2016 Dec; 12(12): e1006070. PMID: 27942025, PMCID: PMC5152916, PII: PPATHOGENS-D-16-01664, DOI: 10.1371/journal.ppat.1006070, ISSN: 1553-7374.

Chumbler NM, Farrow MA, Lapierre LA, Franklin JL, Lacy DB. Clostridium difficile Toxins TcdA and TcdB Cause Colonic Tissue Damage by Distinct Mechanisms. Infect. Immun [electronic-print]. 2016 Oct; 84(10): 2871-7. PMID: 27456833, PMCID: PMC5038081, PII: IAI.00583-16, DOI: 10.1128/IAI.00583-16, ISSN: 1098-5522.

González-Rivera C, Campbell AM, Rutherford SA, Pyburn TM, Foegeding NJ, Barke TL, Spiller BW, McClain MS, Ohi MD, Lacy DB, Cover TL. A Nonoligomerizing Mutant Form of Helicobacter pylori VacA Allows Structural Analysis of the p33 Domain. Infect. Immun [electronic-print]. 2016 Sep; 84(9): 2662-70. PMID: 27382020, PMCID: PMC4995914, PII: IAI.00254-16, DOI: 10.1128/IAI.00254-16, ISSN: 1098-5522.

Smits WK, Lyras D, Lacy DB, Wilcox MH, Kuijper EJ. Clostridium difficile infection. Nat Rev Dis Primers. 2016 Apr 4/7/2016; 2: 16020. PMID: 27158839, PII: nrdp201620, DOI: 10.1038/nrdp.2016.20, ISSN: 2056-676X.

Reyes-Robles T, Lubkin A, Alonzo F, Lacy DB, Torres VJ. Exploiting dominant-negative toxins to combat Staphylococcus aureus pathogenesis. EMBO Rep [print-electronic]. 2016 Mar; 17(3): 428-40. PMID: 26882549, PMCID: PMC4772982, PII: embr.201540994, DOI: 10.15252/embr.201540994, ISSN: 1469-3178.

Quesada-Gómez C, López-Ureña D, Chumbler N, Kroh HK, Castro-Peña C, Rodríguez C, Orozco-Aguilar J, González-Camacho S, Rucavado A, Guzmán-Verri C, Lawley TD, Lacy DB, Chaves-Olarte E. Analysis of TcdB Proteins within the Hypervirulent Clade 2 Reveals an Impact of RhoA Glucosylation on Clostridium difficile Proinflammatory Activities. Infect. Immun. 2016 Jan 1/11/2016; 84(3): 856-65. PMID: 26755157, PMCID: PMC4771349, PII: IAI.01291-15, DOI: 10.1128/IAI.01291-15, ISSN: 1098-5522.

Chumbler NM, Rutherford SA, Zhang Z, Farrow MA, Lisher JP, Farquhar E, Giedroc DP, Spiller BW, Melnyk RA, Lacy DB. Crystal structure of Clostridium difficile toxin A. Nat Microbiol. 2016 Jan 1/11/2016; 1: 15002. PMID: 27571750, PMCID: PMC4976693, PII: nmicrobiol20152, DOI: 10.1038/nmicrobiol.2015.2, ISSN: 2058-5276.

Craven R, Lacy DB. Clostridium sordellii Lethal-Toxin Autoprocessing and Membrane Localization Activities Drive GTPase Glucosylation Profiles in Endothelial Cells. MSphere. 2016 Jan; 1(1): PMID: 27303685, PMCID: PMC4863631, PII: mSphere00012-15, DOI: 10.1128/mSphere.00012-15.

Chumbler NM, Rutherford SA, Zhang Z, Farrow MA, Lisher JP, Farquhar E, Giedroc DP, Spiller BW, Melnyk RA, Lacy DB. Crystal structure of Clostridium difficile toxin A. Nat Microbiol [print-electronic]. 2016; 1: PMID: 27512603, DOI: 10.1038/nmicrobiol.2015.2.

Varela Chavez C, Hoos S, Haustant GM, Chenal A, England P, Blondel A, Pauillac S, Lacy DB, Popoff MR. The catalytic domains of Clostridium sordellii lethal toxin and related large clostridial glucosylating toxins specifically recognize the negatively charged phospholipids phosphatidylserine and phosphatidic acid. Cell. Microbiol [print-electronic]. 2015 Oct; 17(10): 1477-93. PMID: 25882477, DOI: 10.1111/cmi.12449, ISSN: 1462-5822.

Wang X, Yamamoto Y, Wilson LH, Zhang T, Howitt BE, Farrow MA, Kern F, Ning G, Hong Y, Khor CC, Chevalier B, Bertrand D, Wu L, Nagarajan N, Sylvester FA, Hyams JS, Devers T, Bronson R, Lacy DB, Ho KY, Crum CP, McKeon F, Xian W. Cloning and variation of ground state intestinal stem cells. Nature [print-electronic]. 2015 Jun 6/11/2015; 522(7555): 173-8. PMID: 26040716, PII: nature14484, DOI: 10.1038/nature14484, ISSN: 1476-4687.

LaFrance ME, Farrow MA, Chandrasekaran R, Sheng J, Rubin DH, Lacy DB. Identification of an epithelial cell receptor responsible for Clostridium difficile TcdB-induced cytotoxicity. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2015 Jun 6/2/2015; 112(22): 7073-8. PMID: 26038560, PMCID: PMC4460460, PII: 1500791112, DOI: 10.1073/pnas.1500791112, ISSN: 1091-6490.

Zhang Z, Park M, Tam J, Auger A, Beilhartz GL, Lacy DB, Melnyk RA. Translocation domain mutations affecting cellular toxicity identify the Clostridium difficile toxin B pore. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2014 Mar 3/11/2014; 111(10): 3721-6. PMID: 24567384, PMCID: PMC3956163, PII: 1400680111, DOI: 10.1073/pnas.1400680111, ISSN: 1091-6490.

DuMont AL, Yoong P, Liu X, Day CJ, Chumbler NM, James DB, Alonzo F, Bode NJ, Lacy DB, Jennings MP, Torres VJ. Identification of a crucial residue required for Staphylococcus aureus LukAB cytotoxicity and receptor recognition. Infect. Immun [print-electronic]. 2014 Mar; 82(3): 1268-76. PMID: 24379286, PMCID: PMC3958006, PII: IAI.01444-13, DOI: 10.1128/IAI.01444-13, ISSN: 1098-5522.

Farrow MA, Chumbler NM, Lapierre LA, Franklin JL, Rutherford SA, Goldenring JR, Lacy DB. Clostridium difficile toxin B-induced necrosis is mediated by the host epithelial cell NADPH oxidase complex. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2013 Nov 11/12/2013; 110(46): 18674-9. PMID: 24167244, PMCID: PMC3831945, PII: 1313658110, DOI: 10.1073/pnas.1313658110, ISSN: 1091-6490.

Reyes-Robles T, Alonzo F, Kozhaya L, Lacy DB, Unutmaz D, Torres VJ. Staphylococcus aureus leukotoxin ED targets the chemokine receptors CXCR1 and CXCR2 to kill leukocytes and promote infection. Cell Host Microbe. 2013 Oct 10/16/2013; 14(4): 453-9. PMID: 24139401, PMCID: PMC3876884, PII: S1931-3128(13)00325-9, DOI: 10.1016/j.chom.2013.09.005, ISSN: 1934-6069.

Slater LH, Hett EC, Mark K, Chumbler NM, Patel D, Lacy DB, Collier RJ, Hung DT. Identification of novel host-targeted compounds that protect from anthrax lethal toxin-induced cell death. ACS Chem. Biol [print-electronic]. 2013 Apr 4/19/2013; 8(4): 812-22. PMID: 23343607, PMCID: PMC3638717, DOI: 10.1021/cb300555n, ISSN: 1554-8937.

Benefield DA, Dessain SK, Shine N, Ohi MD, Lacy DB. Molecular assembly of botulinum neurotoxin progenitor complexes. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2013 Apr 4/2/2013; 110(14): 5630-5. PMID: 23509303, PMCID: PMC3619295, PII: 1222139110, DOI: 10.1073/pnas.1222139110, ISSN: 1091-6490.

Chambers MG, Pyburn TM, González-Rivera C, Collier SE, Eli I, Yip CK, Takizawa Y, Lacy DB, Cover TL, Ohi MD. Structural analysis of the oligomeric states of Helicobacter pylori VacA toxin. J. Mol. Biol [print-electronic]. 2013 Feb 2/8/2013; 425(3): 524-35. PMID: 23178866, PMCID: PMC3612943, PII: S0022-2836(12)00892-3, DOI: 10.1016/j.jmb.2012.11.020, ISSN: 1089-8638.

Pruitt RN, Chumbler NM, Rutherford SA, Farrow MA, Friedman DB, Spiller B, Lacy DB. Structural determinants of Clostridium difficile toxin A glucosyltransferase activity. J. Biol. Chem [print-electronic]. 2012 Mar 3/9/2012; 287(11): 8013-20. PMID: 22267739, PMCID: PMC3318759, PII: M111.298414, DOI: 10.1074/jbc.M111.298414, ISSN: 1083-351X.

Chumbler NM, Farrow MA, Lapierre LA, Franklin JL, Haslam DB, Goldenring JR, Lacy DB. Clostridium difficile Toxin B causes epithelial cell necrosis through an autoprocessing-independent mechanism. PLoS Pathog [print-electronic]. 2012; 8(12): e1003072. PMID: 23236283, PMCID: PMC3516567, PII: PPATHOGENS-D-12-01408, DOI: 10.1371/journal.ppat.1003072, ISSN: 1553-7374.

Pruitt RN, Lacy DB. Toward a structural understanding of Clostridium difficile toxins A and B. Front Cell Infect Microbiol. 2012; 2: 28. PMID: 22919620, PMCID: PMC3417631, DOI: 10.3389/fcimb.2012.00028, ISSN: 2235-2988.

Mushrush DJ, Koteiche HA, Sammons MA, Link AJ, McHaourab HS, Lacy DB. Studies of the mechanistic details of the pH-dependent association of botulinum neurotoxin with membranes. J. Biol. Chem [print-electronic]. 2011 Jul 7/29/2011; 286(30): 27011-8. PMID: 21652698, PMCID: PMC3143659, PII: M111.256982, DOI: 10.1074/jbc.M111.256982, ISSN: 1083-351X.

Johnson PM, Chen SS, Santomango TS, Williams PE, Lacy DB, McGuinness OP. Continuous low-dose fructose infusion does not reverse glucagon-mediated decrease in hepatic glucose utilization. Metab. Clin. Exp [print-electronic]. 2011 Jun; 60(6): 867-73. PMID: 20940071, PMCID: PMC3736817, PII: S0026-0495(10)00288-X, DOI: 10.1016/j.metabol.2010.08.006, ISSN: 1532-8600.

Gangwer KA, Shaffer CL, Suerbaum S, Lacy DB, Cover TL, Bordenstein SR. Molecular evolution of the Helicobacter pylori vacuolating toxin gene vacA. J. Bacteriol [print-electronic]. 2010 Dec; 192(23): 6126-35. PMID: 20870762, PMCID: PMC2981223, PII: JB.01081-10, DOI: 10.1128/JB.01081-10, ISSN: 1098-5530.

Pruitt RN, Chambers MG, Ng KK, Ohi MD, Lacy DB. Structural organization of the functional domains of Clostridium difficile toxins A and B. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2010 Jul 7/27/2010; 107(30): 13467-72. PMID: 20624955, PMCID: PMC2922184, PII: 1002199107, DOI: 10.1073/pnas.1002199107, ISSN: 1091-6490.

González-Rivera C, Gangwer KA, McClain MS, Eli IM, Chambers MG, Ohi MD, Lacy DB, Cover TL. Reconstitution of Helicobacter pylori VacA toxin from purified components. Biochemistry. 2010 Jul 7/13/2010; 49(27): 5743-52. PMID: 20527875, PMCID: PMC2910095, DOI: 10.1021/bi100618g, ISSN: 1520-4995.

Schmitt J, Karalewitz A, Benefield DA, Mushrush DJ, Pruitt RN, Spiller BW, Barbieri JT, Lacy DB. Structural analysis of botulinum neurotoxin type G receptor binding. Biochemistry. 2010 Jun 6/29/2010; 49(25): 5200-5. PMID: 20507178, PMCID: PMC2894633, DOI: 10.1021/bi100412v, ISSN: 1520-4995.

Ivie SE, McClain MS, Algood HM, Lacy DB, Cover TL. Analysis of a beta-helical region in the p55 domain of Helicobacter pylori vacuolating toxin. BMC Microbiol. 2010; 10: 60. PMID: 20178613, PMCID: PMC2836311, PII: 1471-2180-10-60, DOI: 10.1186/1471-2180-10-60, ISSN: 1471-2180.

Pruitt RN, Chagot B, Cover M, Chazin WJ, Spiller B, Lacy DB. Structure-function analysis of inositol hexakisphosphate-induced autoprocessing in Clostridium difficile toxin A. J. Biol. Chem [print-electronic]. 2009 Aug 8/14/2009; 284(33): 21934-40. PMID: 19553670, PMCID: PMC2755918, PII: M109.018929, DOI: 10.1074/jbc.M109.018929, ISSN: 0021-9258.

Chen SS, Santomango TS, Williams PE, Lacy DB, McGuinness OP. Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2009 May; 296(5): E1172-8. PMID: 19208853, PMCID: PMC2681308, PII: 90821.2008, DOI: 10.1152/ajpendo.90821.2008, ISSN: 0193-1849.

Fischer A, Mushrush DJ, Lacy DB, Montal M. Botulinum neurotoxin devoid of receptor binding domain translocates active protease. PLoS Pathog [print-electronic]. 2008 Dec; 4(12): e1000245. PMID: 19096517, PMCID: PMC2596314, DOI: 10.1371/journal.ppat.1000245, ISSN: 1553-7374.

Ivie SE, McClain MS, Torres VJ, Algood HM, Lacy DB, Yang R, Blanke SR, Cover TL. Helicobacter pylori VacA subdomain required for intracellular toxin activity and assembly of functional oligomeric complexes. Infect. Immun [print-electronic]. 2008 Jul; 76(7): 2843-51. PMID: 18443094, PMCID: PMC2446698, PII: IAI.01664-07, DOI: 10.1128/IAI.01664-07, ISSN: 1098-5522.

Gangwer KA, Mushrush DJ, Stauff DL, Spiller B, McClain MS, Cover TL, Lacy DB. Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2007 Oct 10/9/2007; 104(41): 16293-8. PMID: 17911250, PMCID: PMC2042200, PII: 0707447104, DOI: 10.1073/pnas.0707447104, ISSN: 0027-8424.

Scobie HM, Marlett JM, Rainey GJ, Lacy DB, Collier RJ, Young JA. Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation. PLoS ONE. 2007; 2(3): e329. PMID: 17389920, PMCID: PMC1824706, DOI: 10.1371/journal.pone.0000329, ISSN: 1932-6203.

Scobie HM, Wigelsworth DJ, Marlett JM, Thomas D, Rainey GJ, Lacy DB, Manchester M, Collier RJ, Young JA. Anthrax toxin receptor 2-dependent lethal toxin killing in vivo. PLoS Pathog. 2006 Oct; 2(10): e111. PMID: 17054395, PMCID: PMC1617126, PII: 06-PLPA-RA-0138R2, DOI: 10.1371/journal.ppat.0020111, ISSN: 1553-7374.

Melnyk RA, Hewitt KM, Lacy DB, Lin HC, Gessner CR, Li S, Woods VL, Collier RJ. Structural determinants for the binding of anthrax lethal factor to oligomeric protective antigen. J. Biol. Chem [print-electronic]. 2006 Jan 1/20/2006; 281(3): 1630-5. PMID: 16293620, PII: M511164200, DOI: 10.1074/jbc.M511164200, ISSN: 0021-9258.

Lacy DB, Lin HC, Melnyk RA, Schueler-Furman O, Reither L, Cunningham K, Baker D, Collier RJ. A model of anthrax toxin lethal factor bound to protective antigen. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2005 Nov 11/8/2005; 102(45): 16409-14. PMID: 16251269, PMCID: PMC1283467, PII: 0508259102, DOI: 10.1073/pnas.0508259102, ISSN: 0027-8424.

Krantz BA, Melnyk RA, Zhang S, Juris SJ, Lacy DB, Wu Z, Finkelstein A, Collier RJ. A phenylalanine clamp catalyzes protein translocation through the anthrax toxin pore. Science. 2005 Jul 7/29/2005; 309(5735): 777-81. PMID: 16051798, PMCID: PMC1815389, PII: 309/5735/777, DOI: 10.1126/science.1113380, ISSN: 1095-9203.

Lacy DB, Wigelsworth DJ, Melnyk RA, Harrison SC, Collier RJ. Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2004 Sep 9/7/2004; 101(36): 13147-51. PMID: 15326297, PMCID: PMC516539, PII: 0405405101, DOI: 10.1073/pnas.0405405101, ISSN: 0027-8424.

Wigelsworth DJ, Krantz BA, Christensen KA, Lacy DB, Juris SJ, Collier RJ. Binding stoichiometry and kinetics of the interaction of a human anthrax toxin receptor, CMG2, with protective antigen. J. Biol. Chem [print-electronic]. 2004 May 5/28/2004; 279(22): 23349-56. PMID: 15044490, PII: M401292200, DOI: 10.1074/jbc.M401292200, ISSN: 0021-9258.

Lacy DB, Wigelsworth DJ, Scobie HM, Young JA, Collier RJ. Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2004 Apr 4/27/2004; 101(17): 6367-72. PMID: 15079089, PMCID: PMC404051, PII: 0401506101, DOI: 10.1073/pnas.0401506101, ISSN: 0027-8424.

Mourez M, Yan M, Lacy DB, Dillon L, Bentsen L, Marpoe A, Maurin C, Hotze E, Wigelsworth D, Pimental RA, Ballard JD, Collier RJ, Tweten RK. Mapping dominant-negative mutations of anthrax protective antigen by scanning mutagenesis. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2003 Nov 11/25/2003; 100(24): 13803-8. PMID: 14623961, PMCID: PMC283502, PII: 2436299100, DOI: 10.1073/pnas.2436299100, ISSN: 0027-8424.

Mourez M, Lacy DB, Cunningham K, Legmann R, Sellman BR, Mogridge J, Collier RJ. 2001: a year of major advances in anthrax toxin research. Trends Microbiol. 2002 Jun; 10(6): 287-93. PMID: 12088665, PII: S0966842X02023697, ISSN: 0966-842X.

Cunningham K, Lacy DB, Mogridge J, Collier RJ. Mapping the lethal factor and edema factor binding sites on oligomeric anthrax protective antigen. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2002 May 5/14/2002; 99(10): 7049-53. PMID: 11997439, PMCID: PMC124526, PII: 062160399, DOI: 10.1073/pnas.062160399, ISSN: 0027-8424.

Mogridge J, Cunningham K, Lacy DB, Mourez M, Collier RJ. The lethal and edema factors of anthrax toxin bind only to oligomeric forms of the protective antigen. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2002 May 5/14/2002; 99(10): 7045-8. PMID: 11997437, PMCID: PMC124525, PII: 052160199, DOI: 10.1073/pnas.052160199, ISSN: 0027-8424.

Lacy DB, Mourez M, Fouassier A, Collier RJ. Mapping the anthrax protective antigen binding site on the lethal and edema factors. J. Biol. Chem [print-electronic]. 2002 Jan 1/25/2002; 277(4): 3006-10. PMID: 11714723, PII: M109997200, DOI: 10.1074/jbc.M109997200, ISSN: 0021-9258.

Lacy DB, Collier RJ. Structure and function of anthrax toxin. Curr. Top. Microbiol. Immunol. 2002; 271: 61-85. PMID: 12224524, ISSN: 0070-217X.

Pannifer AD, Wong TY, Schwarzenbacher R, Renatus M, Petosa C, Bienkowska J, Lacy DB, Collier RJ, Park S, Leppla SH, Hanna P, Liddington RC. Crystal structure of the anthrax lethal factor. Nature. 2001 Nov 11/8/2001; 414(6860): 229-33. PMID: 11700563, PII: n35101999, DOI: 10.1038/n35101998, ISSN: 0028-0836.

Lacy DB, Stevens RC. Sequence homology and structural analysis of the clostridial neurotoxins. J. Mol. Biol. 1999 Sep 9/3/1999; 291(5): 1091-104. PMID: 10518945, PII: S0022-2836(99)92945-5, DOI: 10.1006/jmbi.1999.2945, ISSN: 0022-2836.

Lacy DB, Stevens RC. Unraveling the structures and modes of action of bacterial toxins. Curr. Opin. Struct. Biol. 1998 Dec; 8(6): 778-84. PMID: 9914258, ISSN: 0959-440X.

Lacy DB, Tepp W, Cohen AC, DasGupta BR, Stevens RC. Crystal structure of botulinum neurotoxin type A and implications for toxicity. Nat. Struct. Biol. 1998 Oct; 5(10): 898-902. PMID: 9783750, DOI: 10.1038/2338, ISSN: 1072-8368.

Lacy DB, Stevens RC. Recombinant expression and purification of the botulinum neurotoxin type A translocation domain. Protein Expr. Purif. 1997 Nov; 11(2): 195-200. PMID: 9367816, PII: S1046-5928(97)90772-5, DOI: 10.1006/prep.1997.0772, ISSN: 1046-5928.

McGuinness OP, Lacy DB, Ejiofor J, Bagby GG. Hepatic release of tumor necrosis factor in the endotoxin-treated conscious dog. Shock. 1996 May; 5(5): 344-8. PMID: 9156790, ISSN: 1073-2322.

Crimmins, MT, Huang, S, Guise, LE, Lacy DB. Addition of functionalized zinc copper reagents to acetylenic esters: synthesis of 2-carboalkoxy cyclohexenones. Tetrahedron Letters. 1995; 36: 7061-64.

Available Postdoctoral Position Details
Posted: 8/19/2015
please inquire