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James Edward Kirby, M.D.

TitleAssistant Professor of Pathology
InstitutionBeth Israel Deaconess Medical Center
DepartmentPathology
AddressBeth Israel Deaconess Med Ctr
Pathology - YAMINS 309
330 Brookline Ave
Boston MA 02215
Phone617/667-3658
Fax617/667-4533

 Mentoring 
 current student opportunities
Available: 08/14/13, Expires: 07/31/18

Bartonella are the most prevalent cause of chronic blood stream infection in mammals. These bacteria are transmitted by blood sucking arthropod vectors. Infectious prevalence exceed 50% in some mammals (cattle, rodents, feral versions of our mammalians pets). Human infection is primarily zoonotic (cat scratch disease), although several Bartonella species are primary human pathogens (B. quintana, B. bacilliformis). Human infection can lead to devastating complications (endocarditis, retinitis, encephalopathy, angioproliferative tumor formation). It is recognized that human disease burden is greatly underappreciated because of the difficulty in primary culturing of these organisms. Remarkably, several Bartonella species have the property of inducing angiogenesis (new blood vessel formation) in humans. These also have the remarkable ability to persist in their hosts, for weeks to months or longer. The basis for this persistence is largely unknown and will likely teach us about novel strategies used by pathogens to undermine host defenses. We have developed several tissue culture and animals models for modeling human infection and are using them to investigate disease pathogenesis. I also spearheaded the Bartonella genome project, where we have sequenced most of the available Bartonella species. Projects available will seek to understand the remarkable ability to persist in the host through use of in vitro or in vivo models, and use of several high level microscopy techniques including the potential use of super-resolution STORM microscopy. In silico investigation of Bartonella pathogenesis would be a separate line of investigation through bioinformatic analysis of genome sequence available through the Bartonella genome project. Molecular cloning/recombinant DNA experience desirable for wet bench work. 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.

Available: 08/01/13, Expires: 03/31/15

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.

Available: 08/01/12, Expires: 09/02/14

Multi-drug resistance is compromising our ability to treat bacterial infections. Therefore, new classes of anti-microbials are urgently needed. We have validated a high throughput screening approach to identify small molecules that target a critical interaction between pathogen and host, specifically a secretion machinery used by a large number of pathogens to inject virulence factors into host cells. We believe this strategy will allow us to define a new class of therapeutics that targets pathogens while sparing normal flora. Agents will be validated in both in vitro and in vivo infection models with the goal of developing human therapeutics.

Bartonella pathogenesis[login at prompt]
Available: 07/09/12, Expires: 12/09/14

Bartonella are the most common cause of chronic systemic infection in mammals. Prevalence of up to 90% may be found in mammals ranging from rodents to cattle to dogs, cats and bats. As such they represent an outstanding model for investigating host-pathogen interaction and the ability of pathogens to cause chronic bloodstream infection.


 Bibliographic 
 selected publications
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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  1. 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.
    View in: PubMed
  2. 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.
    View in: PubMed
  3. 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 6; 11(1):75-90.
    View in: PubMed
  4. 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.
    View in: PubMed
  5. 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.
    View in: PubMed
  6. 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; 5(3):e9505.
    View in: PubMed
  7. 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.
    View in: PubMed
  8. 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.
    View in: PubMed
  9. 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.
    View in: PubMed
  10. 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.
    View in: PubMed
  11. Chiaraviglio L, Brown DA, Kirby JE. Infection of cultured human endothelial cells by Legionella pneumophila. PLoS One. 2008; 3(4):e2012.
    View in: PubMed
  12. 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.
    View in: PubMed
  13. 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.
    View in: PubMed
  14. 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.
    View in: PubMed
  15. Duong S, Chiaraviglio L, Kirby JE. Histopathology in a murine model of anthrax. Int J Exp Pathol. 2006 Apr; 87(2):131-7.
    View in: PubMed
  16. Kirby JE. In vitro model of Bartonella henselae-induced angiogenesis. Infect Immun. 2004 Dec; 72(12):7315-7.
    View in: PubMed
  17. Kirby JE. Anthrax lethal toxin induces human endothelial cell apoptosis. Infect Immun. 2004 Jan; 72(1):430-9.
    View in: PubMed
  18. Kirby JE, Nekorchuk DM. Bartonella-associated endothelial proliferation depends on inhibition of apoptosis. Proc Natl Acad Sci U S A. 2002 Apr 2; 99(7):4656-61.
    View in: PubMed
  19. Kirby JE, Isberg RR. Legionnaires' disease: the pore macrophage and the legion of terror within. Trends Microbiol. 1998 Jul; 6(7):256-8.
    View in: PubMed
  20. Kirby JE, Vogel JP, Andrews HL, Isberg RR. Evidence for pore-forming ability by Legionella pneumophila. Mol Microbiol. 1998 Jan; 27(2):323-36.
    View in: PubMed
  21. 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.
    View in: PubMed
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