James Edward Kirby, M.D.
|Title||Assistant Professor of Pathology|
|Institution||Beth Israel Deaconess Medical Center|
|Address||Beth Israel Deaconess Med Ctr|
Pathology - YAMINS 309
330 Brookline Ave
Boston MA 02215
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.
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.
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