Center For AIDS Research

March 24, 2016: Special Edition

The Network News
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Special Edition: March 24, 2016
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World TB Day 2016:

CFAR Makes a Difference
    Unite Against TB

Back in the 1990s the state of Georgia ranked 7th in the nation for number of tuberculosis patients (5,586 cases) and if Grady Memorial Hospital were a state it would have ranked 28th in the nation (1,378 cases).

By 2014, Georgia cases had dropped to n=335 and, if it were a state, Grady would now come in at 34th in the nation (56 cases). BIG changes for the better.

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World TB Day 2016:
43 million: Lives saved globally through effective TB diagnosis and treatment, 2000-2014
480 thousand: Number of people globally who developed multi-drug resistant (MDR) TB in 2014
4 thousand: Number of people globally who die from TB each day

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CFAR Unites Against TB:
As we comemorate Global TB Day 2016 we want to highlight some of the amazing research and work done by Emory CFAR investigators who are addressing the local as well as the global epidemic.

     Hank Blumberg

For the last 12 years Hank Blumberg has spearheaded the Emory-Georgia TB Research Training Program (D43TW007124) to enhance TB-related research capacity in the OTHER Georgia, a country that WHO has designated one of the globe's 27 high burden MDR-TB countries. In Africa, Hank's Ethiopia-Emory TB Research Training Program (D43TW009127) is in its 4th year of increasing TB research capacity in a country that WHO has designated as one of the "high burden countries" that account for >80% of the global burden of TB.

Closer to home, Hank is also the PI of the NIAID-funded Tuberculosis Research Units (TBRU) network. The Emory-led TBRU (U19AI111211) comprises four research centers (Emory University, Boston Medical Center, Brigham and Women's Hospital, Cornell Medical College) and will bring approximately $18.7 million to Emory over seven years.

• • Click Here for Update to the Information Below • •

Jyothi Rengarajan     

Jyothi Rengarajan is PI of a TBRU subproject (7780) that is seeking to identify the human Mtb-specific T cell signatures that are associated with the control or elminiation of MTB infection in humans. She is also PI of an R56 (R56AI083366) that is looking at why Mtb-specific T cell responses are poorly protective against TB and an R21 (R21AI117162) that is seeking to determine if blocking the functions of a key Mtb immunomodulatory protease Hip1 will lead to accelerated clearance of MTB by antibiotics -- making a shortened treatment regimen possible (current regimens are long and poorly adhered to).

     Francois Villinger

Francois Villinger also has a TBRU subproject (7784); this one will identify the immune signatures associated with control of Mtb infection as latent infection, either spontaneously or upon therapy, in rhesus macaques. Along with Jyothi Rengarajan's sub-project and a second one by Joel Ernst (from NYU) on human T-cell responses that permit progression to active TB, Francois' project will (hopefully) help pave the way for testing novel TB therapeutic avenues in the future by using a primate model to address correlates of protection, which will serve as references for future vaccine attempts.

Neel Gandhi     

Neel Gandhi runs the TBRU Clinical Core (7788) and also has a K24 (K24AI114444) that gives him protected time to expand his patient-oiented research in TB and HIV while simultaneously mentoring the next generation of researchers focusing on these areas. Neel is also the PI of a project (R01AI087465) that is investigating the impact of HIV, antiretroviral therapy and TB genotype on survival in multi-drug resistant (MDR) TB and a second R01 (R01AI089349) that is examining extensively drug-resistant (XDR) TB transmission patterns in a high HIV-prevalent, rural area of South Africa.

     Cheryl Day

Like many of us, Cheryl Day wonders why co-infection with HIV is the single greatest risk factor for reactivation of latent TB infection (LTBI) and progression to active TB disease. To look more deeply into this phenomena, Cheryl has an RO1 (R01AI111948) that seeks to understand how co-infection with HIV perturbs innate and adaptive immune control of latent TB, through studying the natural kller (NK) cell-mediated regulation of T-cell immunity in TB/HIV co-infection. This work will contribute to the rational design of TB vaccines and immunotherapeutic approaches for people with HIV and TB.

Roy Sutliff     

Oxidative stress is central to the pathogenesis of both HIV and MTB. Roy Sutliff thinks that a significant bottleneck exists in investigating this, primarily because of a lack of non-invasive tools to dynamically measure HIV-induced redox stress at the cellular and sub- cellular levels and the absence of appropriate animal models for this purpose. He proposes to begin addressing this with a project (R21AI106386) that will use a novel genetically encoded green fluorescent protein based redox bioprobe and HIV-1 transgenic mice to examine the role of Oxido-reductive stress in regulating HIV-TB coinfection.

     Russell Kempker

As if TB isn't enough all on its own, the global emergence of multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB is making a bad thing a lot worse. Russell Kempker has made studying drug resistance in TB the basis of his NIH career development award (K23AI103044). He also has new funding (R21AI122001) for a clinical pharmacology study of a novel drug regimen for pre XDR and XDR TB that includes bedaquiline, linezolid, and clofazimine. The study will look at rates and genetic determinants of resistance in hopes of improving treatment outcomes for patients with drug-resistant TB.

Dan Kalman     

As mentioned above, existing therapies for MDR-TB and XDR-TB have dismal track records. Enter Dan Kalman who is also tacking this problem with a new award (UH2AI122320) to develop Gleevec for TB and TB/HIV. Gleevec is a well tolerated cancer drug that, we hope, will also serve as a "host- directed therapeutic (HDT)" for MDR and XDR TB infections and HIV/TB co-infections due to its ability to act synergistically with antibiotics, its effectiveness against antibiotic-resistant mycobacteria, and (fingers crossed) its low propensity to engender additional resistance.

GO TEAM CFAR!!!

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The Network News is a periodic email, detailing HIV/AIDS related events, funding opportunities, and achievements of CFAR members. If you have items that you wish to have included, please send them to us at cfar@emory.edu by Friday of each week. Please put "The Network News" in the subject line.

The Network News is distributed to CFAR members and fans by email every Tuesday. Except when it isn't.

Editor, Kimberley (Kimbi) Sessions Hagen, EdD

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