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James Edward Kirby, M.D.

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Mentoring
Available: 08/01/13, Expires: 03/31/20

Emerging multi-drug resistance is compromising our ability to treat bacterial infection. It is predicted that over the next decade we will loose the ability to treat many invasive infections. New anti-infective strategies are urgently needed. Therefore, my laboratory is seeking to identify novel antimicrobials that:

(1) interfere with pathogen-host interaction, and

(2) engage non-traditional targets in bacteria associated with multi-drug resistance.

Regarding the former, we are targeting specialized secretion systems required by some Gram negative bacteria for virulence.

A student's project may involve high throughput screening assay development, including genetic modification of bacteria to permit novel assay readout; high throughput screening for novel antimicrobials; and assays to assess antimicrobial potential of drug candidates using in vitro and/or in vivo infection models. As potential therapeutic candidates are identified, the project may also involve collaborative efforts to understand and improve therapeutic potency (so called structure-activity relationship studies). Students will become acquainted with many different aspects of the drug discovery process and will develop expertise in several techniques depending on the project (tissue culture, bacteriology, molecular biology, and high throughput screening approaches for drug discovery). My laboratory is located in a new, state-of-the-art research building around the corner from the HMS Quad (the Clinical Life Science Building, 3 Blackfan Circle). I have had a previous SIM student in my laboratory. I encourage students to contact me to discuss several, highly medically relevant projects that may be of mutual interest. See www.kirbylab.org for more information about my laboratory


Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R21AI146485 (KIRBY, JAMES E) May 15, 2019 - Apr 30, 2021
    NIH/NIAID
    Fusidic acid derivatization to enhance entry into Gram-negative pathogens
    Role: Principal Investigator
  2. R21AI140212 (MANETSCH, ROMAN) Mar 1, 2019 - Feb 28, 2021
    NIH/NIAID
    Development of Streptothricin Class Antimicrobials as Novel Therapeutics
    Role: Co-Principal Investigator
  3. R03AI144196 (KIRBY, JAMES E) Feb 8, 2019 - Jan 31, 2021
    NIH/NIAID
    Targeted modification of the apramycin 2-deoxystreptamine ring to block aminoglycoside modifying enzyme-based inactivation and enhance potency against multidrug-resistant Gram-negative pathogens
    Role: Principal Investigator
  4. R21AI142040 (KIRBY, JAMES E) Nov 13, 2018 - Oct 31, 2020
    NIH/NIAID
    Apramycin scaffold exploration using novel glycochemistry and SAR studies to enhance activity against Acinetobacter baumannii and other multidrug-resistant Gram-negative pathogens
    Role: Principal Investigator
  5. R21AI130434 (KIRBY, JAMES E) May 15, 2018 - Apr 30, 2020
    NIH/NIAID
    Microscopy-Based Antimicrobial Susceptibility Testing (MAST)
    Role: Principal Investigator

Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  1. Kang YS, Kirby JE. A chemical genetics screen reveals influence of p38 map kinase and autophagy on phagosome development and intracellular replication of Brucella neotomae in macrophages. Infect Immun. 2019 Jun 03. PMID: 31160361.
    Citations:    
  2. Brennan-Krohn T, Kirby JE. Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method. J Vis Exp. 2019 Apr 18; (146). PMID: 31058886.
    Citations:    
  3. Riedel S, Vijayakumar D, Berg G, Kang AD, Smith KP, Kirby JE. Evaluation of apramycin against spectinomycin-resistant and -susceptible strains of Neisseria gonorrhoeae. J Antimicrob Chemother. 2019 Jan 27. PMID: 30689929.
    Citations:    Fields:    
  4. Kang YS, Brown DA, Kirby JE. Brucella neotomae Recapitulates Attributes of Zoonotic Human Disease in a Murine Infection Model. Infect Immun. 2019 01; 87(1). PMID: 30373892.
    Citations:    Fields:    
  5. Brennan-Krohn T, Pironti A, Kirby JE. Synergistic Activity of Colistin-Containing Combinations against Colistin-Resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2018 Oct; 62(10). PMID: 30061285.
    Citations:    Fields:    
  6. Smith KP, Kirby JE. The Inoculum Effect in the Era of Multidrug Resistance: Minor Differences in Inoculum Have Dramatic Effect on MIC Determination. Antimicrob Agents Chemother. 2018 08; 62(8). PMID: 29784837.
    Citations:    Fields:    
  7. Gite S, Archambault D, Cappillino MP, Cunha D, Dorich V, Shatova T, Tempesta A, Walsh B, Walsh JA, Williams A, Kirby JE, Bowers J, Straus D. A Rapid, Accurate, Single Molecule Counting Method Detects Clostridium difficile Toxin B in Stool Samples. Sci Rep. 2018 May 30; 8(1):8364. PMID: 29849171.
    Citations:    Fields:    
  8. Truelson KA, Brennan-Krohn T, Smith KP, Kirby JE. Evaluation of apramycin activity against methicillin-resistant, methicillin-sensitive, and vancomycin-intermediate Staphylococcus aureus clinical isolates. Diagn Microbiol Infect Dis. 2018 Oct; 92(2):168-171. PMID: 29934071.
    Citations:    Fields:    Translation:HumansCells
  9. Kang AD, Smith KP, Berg AH, Truelson KA, Eliopoulos GM, McCoy C, Kirby JE. Efficacy of Apramycin against Multidrug-Resistant Acinetobacter baumannii in the Murine Neutropenic Thigh Model. Antimicrob Agents Chemother. 2018 04; 62(4). PMID: 29339396.
    Citations:    Fields:    
  10. Smith KP, Kang AD, Kirby JE. Automated Interpretation of Blood Culture Gram Stains by Use of a Deep Convolutional Neural Network. J Clin Microbiol. 2018 03; 56(3). PMID: 29187563.
    Citations:    Fields:    
  11. Brennan-Krohn T, Truelson KA, Smith KP, Kirby JE. Screening for synergistic activity of antimicrobial combinations against carbapenem-resistant Enterobacteriaceae using inkjet printer-based technology. J Antimicrob Chemother. 2017 10 01; 72(10):2775-2781. PMID: 29091221.
    Citations: 1     Fields:    Translation:HumansCells
  12. Smith KP, Richmond DL, Brennan-Krohn T, Elliott HL, Kirby JE. Development of MAST: A Microscopy-Based Antimicrobial Susceptibility Testing Platform. SLAS Technol. 2017 12; 22(6):662-674. PMID: 28837780.
    Citations:    Fields:    Translation:HumansCells
  13. Brennan-Krohn T, Yoon E, Nishino M, Kirby JE, Riedel S. Arthroconidia in lung tissue: an unusual histopathological finding in pulmonary coccidioidomycosis. Hum Pathol. 2018 01; 71:55-59. PMID: 28778515.
    Citations:    Fields:    Translation:HumansCells
  14. Chen A, Smith KP, Whitfield BA, Zucchi PC, Lasco TM, Bias TE, Kirby JE, Hirsch EB. Activity of minocycline against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae clinical isolates, with comparison to doxycycline and tigecycline. Diagn Microbiol Infect Dis. 2017 Aug; 88(4):365-367. PMID: 28535946.
    Citations:    Fields:    Translation:HumansCells
  15. Brennan-Krohn T, Smith KP, Kirby JE. The Poisoned Well: Enhancing the Predictive Value of Antimicrobial Susceptibility Testing in the Era of Multidrug Resistance. J Clin Microbiol. 2017 08; 55(8):2304-2308. PMID: 28468856.
    Citations: 2     Fields:    
  16. Kang YS, Kirby JE. Promotion and Rescue of Intracellular Brucella neotomae Replication during Coinfection with Legionella pneumophila. Infect Immun. 2017 05; 85(5). PMID: 28264909.
    Citations: 1     Fields:    Translation:HumansAnimalsCells
  17. Kang AD, Smith KP, Eliopoulos GM, Berg AH, McCoy C, Kirby JE. Invitro Apramycin Activity against multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Diagn Microbiol Infect Dis. 2017 Jun; 88(2):188-191. PMID: 28341099.
    Citations: 3     Fields:    Translation:HumansAnimalsCells
  18. Bryan AW, Qian Q, Kirby JE. Photo Quiz: A Man with Fever and Headache. J Clin Microbiol. 2017 02; 55(2):351. PMID: 28122992.
    Citations:    Fields:    Translation:Humans
  19. Bryan AW, Qian Q, Kirby JE. Answer to February 2017 Photo Quiz. J Clin Microbiol. 2017 02; 55(2):660-661. PMID: 28122997.
    Citations:    Fields:    Translation:Humans
  20. Kirby JE, Branch-Elliman W, LaSalvia MT, Longhi L, MacKechnie M, Urman G, Baldini LM, Muriel FR, Sullivan B, Yassa DS, Gold HS, Wagner TK, Diekema DJ, Wright SB. Investigation of a Candida guilliermondii Pseudo-outbreak Reveals a Novel Source of Laboratory Contamination. J Clin Microbiol. 2017 04; 55(4):1080-1089. PMID: 28100597.
    Citations:    Fields:    Translation:HumansAnimalsPHPublic Health
  21. Cerqueira GC, Earl AM, Ernst CM, Grad YH, Dekker JP, Feldgarden M, Chapman SB, Reis-Cunha JL, Shea TP, Young S, Zeng Q, Delaney ML, Kim D, Peterson EM, O'Brien TF, Ferraro MJ, Hooper DC, Huang SS, Kirby JE, Onderdonk AB, Birren BW, Hung DT, Cosimi LA, Wortman JR, Murphy CI, Hanage WP. Multi-institute analysis of carbapenem resistance reveals remarkable diversity, unexplained mechanisms, and limited clonal outbreaks. Proc Natl Acad Sci U S A. 2017 01 31; 114(5):1135-1140. PMID: 28096418.
    Citations: 11     Fields:    Translation:HumansCellsPHPublic Health
  22. Smith KP, Brennan-Krohn T, Weir S, Kirby JE. Improved Accuracy of Cefepime Susceptibility Testing for Extended-Spectrum-Beta-Lactamase-Producing Enterobacteriaceae with an On-Demand Digital Dispensing Method. J Clin Microbiol. 2017 02; 55(2):470-478. PMID: 27903600.
    Citations: 4     Fields:    Translation:HumansCells
  23. Chiaraviglio L, Kang YS, Kirby JE. High Throughput, Real-time, Dual-readout Testing of Intracellular Antimicrobial Activity and Eukaryotic Cell Cytotoxicity. J Vis Exp. 2016 11 16; (117). PMID: 27911388.
    Citations: 1     Fields:    Translation:AnimalsCells
  24. Smith KP, Kirby JE. How inkjet printing technology can defeat multidrug-resistant pathogens. Future Microbiol. 2016 10; 11:1375-1377. PMID: 27785916.
    Citations: 3     Fields:    Translation:HumansCells
  25. Smith KP, Kirby JE. Evaluation of apramycin activity against carbapenem-resistant and -susceptible strains of Enterobacteriaceae. Diagn Microbiol Infect Dis. 2016 Dec; 86(4):439-441. PMID: 27745736.
    Citations: 3     Fields:    Translation:HumansCells
  26. Hale AJ, LaSalvia M, Kirby JE, Kimball A, Baden R. Fatal purpura fulminans and Waterhouse-Friderichsen syndrome from fulminant Streptococcus pneumoniae sepsis in an asplenic young adult. IDCases. 2016; 6:1-4. PMID: 27583208.
    Citations: 1     
  27. Yang L, Kirby JE, Sunwoo H, Lee JT. Female mice lacking Xist RNA show partial dosage compensation and survive to term. Genes Dev. 2016 08 01; 30(15):1747-60. PMID: 27542829.
    Citations: 10     Fields:    Translation:AnimalsCells
  28. Smith KP, Kirby JE. Verification of an Automated, Digital Dispensing Platform for At-Will Broth Microdilution-Based Antimicrobial Susceptibility Testing. J Clin Microbiol. 2016 09; 54(9):2288-93. PMID: 27335151.
    Citations: 7     Fields:    Translation:HumansCells
  29. Hale A, Kirby JE, Albrecht M. Fatal Spontaneous Clostridium bifermentans Necrotizing Endometritis: A Case Report and Literature Review of the Pathogen. Open Forum Infect Dis. 2016 Apr; 3(2):ofw095. PMID: 27419167.
    Citations: 3     
  30. Hirsch EB, Zucchi PC, Chen A, Raux BR, Kirby JE, McCoy C, Eliopoulos GM. Susceptibility of Multidrug-Resistant Gram-Negative Urine Isolates to Oral Antibiotics. Antimicrob Agents Chemother. 2016 05; 60(5):3138-40. PMID: 26883704.
    Citations: 1     Fields:    
  31. Smith KP, Kirby JE. Validation of a High-Throughput Screening Assay for Identification of Adjunctive and Directly Acting Antimicrobials Targeting Carbapenem-Resistant Enterobacteriaceae. Assay Drug Dev Technol. 2016 Apr; 14(3):194-206. PMID: 27045615.
    Citations: 2     Fields:    Translation:Cells
  32. Qian Q, Urman G, Cederroth T, Najarian R, Kirby JE. Answer to April 2016 Photo Quiz. J Clin Microbiol. 2016 Apr; 54(4):1177. PMID: 27016595; PMCID: PMC4809941.
    Citations:    
  33. Qian Q, Urman G, Cederroth T, Najarian R, Kirby JE. Photo Quiz: A Man with Fever and Cough. J Clin Microbiol. 2016 Apr; 54(4):825; discussion 1177. PMID: 27016589.
    Citations:    Fields:    Translation:HumansAnimals
  34. Sells RE, Chen CA, Wong MT, Zimarowski MJ, Kirby JE, Joyce RM, Wu PA. Continuous positive airway pressure-associated cutaneous amoebiasis in an immunosuppressed patient. Br J Dermatol. 2016 Mar; 174(3):625-8. PMID: 26474324.
    Citations:    Fields:    Translation:HumansAnimals
  35. Harris RM, Arnaout R, Koziel H, Folch E, Majid A, Kirby JE. Utility of microbiological testing of thoracic lymph nodes sampled by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with mediastinal lymphadenopathy. Diagn Microbiol Infect Dis. 2016 Feb; 84(2):170-4. PMID: 26602949.
    Citations: 1     Fields:    Translation:Humans
  36. Hirsch EB, Raux BR, Zucchi PC, Kim Y, McCoy C, Kirby JE, Wright SB, Eliopoulos GM. Activity of fosfomycin and comparison of several susceptibility testing methods against contemporary urine isolates. Int J Antimicrob Agents. 2015 Dec; 46(6):642-7. PMID: 26498988.
    Citations: 5     Fields:    Translation:HumansCells
  37. Chiaraviglio L, Kirby JE. High-Throughput Intracellular Antimicrobial Susceptibility Testing of Legionella pneumophila. Antimicrob Agents Chemother. 2015 Dec; 59(12):7517-29. PMID: 26392509.
    Citations: 3     Fields:    Translation:HumansCells
  38. Harris RM, Stillman IE, Goldsmith JD, Qian Q, Kirby JE. Pathological rib fracture and soft tissue mass simulating malignancy--Cryptococcus, an unsuspected culprit. Diagn Microbiol Infect Dis. 2015 Mar; 81(3):189-91. PMID: 25583128.
    Citations:    Fields:    Translation:HumansAnimals
  39. Chiaraviglio L, Kirby JE. Evaluation of impermeant, DNA-binding dye fluorescence as a real-time readout of eukaryotic cell toxicity in a high throughput screening format. Assay Drug Dev Technol. 2014 May; 12(4):219-28. PMID: 24831788.
    Citations: 5     Fields:    Translation:HumansCells
  40. Cheng A, Kirby JE. Evaluation of the Hologic gen-probe PANTHER, APTIMA Combo 2 assay in a tertiary care teaching hospital. Am J Clin Pathol. 2014 Mar; 141(3):397-403. PMID: 24515768.
    Citations: 1     Fields:    Translation:HumansCells
  41. Qian Q, Eichelberger K, Kirby JE. Rapid identification of Staphylococcus aureus directly from Bactec blood culture broth by the BinaxNOW S. aureus test. J Clin Microbiol. 2014 Jan; 52(1):319-20. PMID: 24153135.
    Citations: 1     Fields:    Translation:HumansCells
  42. Yildirim E, Kirby JE, Brown DE, Mercier FE, Sadreyev RI, Scadden DT, Lee JT. Xist RNA is a potent suppressor of hematologic cancer in mice. Cell. 2013 Feb 14; 152(4):727-42. PMID: 23415223.
    Citations: 140     Fields:    Translation:AnimalsCells
  43. Anguera MC, Sadreyev R, Zhang Z, Szanto A, Payer B, Sheridan SD, Kwok S, Haggarty SJ, Sur M, Alvarez J, Gimelbrant A, Mitalipova M, Kirby JE, Lee JT. Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes. Cell Stem Cell. 2012 Jul 06; 11(1):75-90. PMID: 22770242.
    Citations: 35     Fields:    Translation:HumansAnimalsCells
  44. Cheng A, Qian Q, Kirby JE. Evaluation of the Abbott RealTime CT/NG assay in comparison to the Roche Cobas Amplicor CT/NG assay. J Clin Microbiol. 2011 Apr; 49(4):1294-300. PMID: 21325546.
    Citations: 12     Fields:    Translation:HumansCells
  45. Chiaraviglio L, Duong S, Brown DA, Birtles RJ, Kirby JE. An immunocompromised murine model of chronic Bartonella infection. Am J Pathol. 2010 Jun; 176(6):2753-63. PMID: 20395436.
    Citations: 7     Fields:    Translation:HumansAnimalsCells
  46. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One. 2010 Mar 03; 5(3):e9505. PMID: 20209079.
    Citations: 179     Fields:    Translation:HumansAnimals
  47. Qian Q, Venkataraman L, Kirby JE, Gold HS, Yamazumi T. Direct detection of methicillin resistance in Staphylococcus aureus in blood culture broth by use of a penicillin binding protein 2a latex agglutination test. J Clin Microbiol. 2010 Apr; 48(4):1420-1. PMID: 20129965.
    Citations: 4     Fields:    Translation:HumansCells
  48. Pollock NR, Duong S, Cheng A, Han LL, Smole S, Kirby JE. Ruling out novel H1N1 influenza virus infection with direct fluorescent antigen testing. Clin Infect Dis. 2009 Sep 15; 49(6):e66-8. PMID: 19681710.
    Citations: 19     Fields:    Translation:HumansCells
  49. Wang Y, Kirby JE, Qian Q. Effective use of JC virus PCR for diagnosis of progressive multifocal leukoencephalopathy. J Med Microbiol. 2009 Feb; 58(Pt 2):253-5. PMID: 19141745.
    Citations: 9     Fields:    Translation:HumansCells
  50. Kirby JE, Delaney M, Qian Q, Gold HS. Optimal use of Myco/F lytic and standard BACTEC blood culture bottles for detection of yeast and mycobacteria. Arch Pathol Lab Med. 2009 Jan; 133(1):93-6. PMID: 19123744.
    Citations: 2     Fields:    Translation:AnimalsCells
  51. Chiaraviglio L, Brown DA, Kirby JE. Infection of cultured human endothelial cells by Legionella pneumophila. PLoS One. 2008 Apr 23; 3(4):e2012. PMID: 18431493.
    Citations: 6     Fields:    Translation:HumansCells
  52. Wang Y, Doucette S, Qian Q, Kirby JE. Yield of primary and repeat induced sputum testing for Pneumocystis jiroveci in human immunodeficiency virus-positive and -negative patients. Arch Pathol Lab Med. 2007 Oct; 131(10):1582-4. PMID: 17922597.
    Citations: 1     Fields:    Translation:HumansAnimals
  53. Qian Q, Eichelberger K, Kirby JE. Rapid identification of Staphylococcus aureus in blood cultures by use of the direct tube coagulase test. J Clin Microbiol. 2007 Jul; 45(7):2267-9. PMID: 17522280.
    Citations: 12     Fields:    Translation:HumansCells
  54. Konstantinopoulos PA, Kirby JE, Miller KB, Dezube BJ. Babesiosis masquerading as recurrent immune thrombocytopenic purpura in a splenectomized patient. Ann Hematol. 2006 Oct; 85(10):739-40. PMID: 16705453.
    Citations:    Fields:    Translation:HumansCells
  55. Duong S, Chiaraviglio L, Kirby JE. Histopathology in a murine model of anthrax. Int J Exp Pathol. 2006 Apr; 87(2):131-7. PMID: 16623757.
    Citations: 7     Fields:    Translation:AnimalsCells
  56. Kirby JE. In vitro model of Bartonella henselae-induced angiogenesis. Infect Immun. 2004 Dec; 72(12):7315-7. PMID: 15557658.
    Citations: 8     Fields:    Translation:HumansCells
  57. Kirby JE. Anthrax lethal toxin induces human endothelial cell apoptosis. Infect Immun. 2004 Jan; 72(1):430-9. PMID: 14688124.
    Citations: 61     Fields:    Translation:HumansCells
  58. Kirby JE, Nekorchuk DM. Bartonella-associated endothelial proliferation depends on inhibition of apoptosis. Proc Natl Acad Sci U S A. 2002 Apr 02; 99(7):4656-61. PMID: 11904386.
    Citations: 32     Fields:    Translation:AnimalsCells
  59. Kirby JE, Isberg RR. Legionnaires' disease: the pore macrophage and the legion of terror within. Trends Microbiol. 1998 Jul; 6(7):256-8. PMID: 9717211.
    Citations: 15     Fields:    Translation:HumansCells
  60. Kirby JE, Vogel JP, Andrews HL, Isberg RR. Evidence for pore-forming ability by Legionella pneumophila. Mol Microbiol. 1998 Jan; 27(2):323-36. PMID: 9484888.
    Citations: 90     Fields:    Translation:AnimalsCells
  61. Kirby JE, Laposata M. The nature and extent of training activities in clinical pathology required for effective consultation on laboratory test selection and interpretation. Arch Pathol Lab Med. 1997 Nov; 121(11):1163-7. PMID: 9372742.
    Citations:    Fields:    Translation:Humans
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Funded by the NIH/NCATS Clinical and Translational Science Award (CTSA) program, grant number UL1TR001102, and through institutional support from Harvard University, Harvard Medical School, Harvard T.H. Chan School of Public Health, Beth Israel Deaconess Medical Center, Boston Children's Hospital, Brigham and Women's Hospital, Massachusetts General Hospital and the Dana Farber Cancer Institute.