The Immune Mechanisms and Pathogenesis Working Group (WG1) has capitalized on major institutional strengths in immunology and host defense to develop a highly interactive and successful network of 40 CFAR investigators, including researchers with basic and translational backgrounds. Collectively they have published 526 peer-reviewed publications during the last funding cycle on the immunological determinants of HIV disease pathogenesis. Seminal studies performed by WG1 investigators have led the HIV research field into recognition of the importance of immune activation and inflammation in HIV pathogenesis. Specifically the group has shown that indices of inflammation and coagulation are key predictors (not just concomitants) of the clinical complications of treated HIV infection. The key scientific objectives for the next few years are to rigorously define the immunopathogenic drivers and pursue studies in the following three key opportunity areas: (i) Molecular mechanisms for enhanced systemic inflammation and clinical complications in HIV disease (ii) Immune failure and immune restoration (iii) Innate mucosal defenses against HIV Thus the overall scientific goal of this Working Group is to provide a new understanding of disease progression in the ART era and to develop and test interventional strategies that will improve outcomes for patients. The group achieves these objectives by initiating and sustaining collaborative projects among its members.
The Specific Aims of WG1 are: ? To develop new interactions among investigators from various disciplines ? To stimulate the formation of multi-investigator projects ? To stimulate cross-fertilization between working groups The research pursued by WG1 investigators is linked intimately with the goals of the Virology and Cure WG2 and the HIV and Co-Infections and Co-Morbidities WG3 and there is frequent cross-fertilization between the groups.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Center Core Grants (P30)
Project #
5P30AI036219-24
Application #
9686009
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Beaubien, Candice M
Project Start
Project End
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
24
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Martinez, Leonardo; Handel, Andreas; Shen, Ye et al. (2018) A Prospective Validation of a Clinical Algorithm to Detect Tuberculosis in Child Contacts. Am J Respir Crit Care Med 197:1214-1216
Fitzgerald, Wendy; Freeman, Michael L; Lederman, Michael M et al. (2018) A System of Cytokines Encapsulated in ExtraCellular Vesicles. Sci Rep 8:8973
Dazard, Jean-Eudes; Ishwaran, Hemant; Mehlotra, Rajeev et al. (2018) Ensemble survival tree models to reveal pairwise interactions of variables with time-to-events outcomes in low-dimensional setting. Stat Appl Genet Mol Biol 17:
Mukherjee, Pranab K; Chandra, Jyotsna; Retuerto, Mauricio et al. (2018) Dysbiosis in the oral bacterial and fungal microbiome of HIV-infected subjects is associated with clinical and immunologic variables of HIV infection. PLoS One 13:e0200285
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Tomalka, Amanda G; Resto-Garay, Ivelisse; Campbell, Kerry S et al. (2018) In vitro Evidence That Combination Therapy With CD16-Bearing NK-92 Cells and FDA-Approved Alefacept Can Selectively Target the Latent HIV Reservoir in CD4+ CD2hi Memory T Cells. Front Immunol 9:2552
Kalayjian, Robert C; Albert, Jeffrey M; Cremers, Serge et al. (2018) Women have enhanced bone loss associated with phosphaturia and CD4+ cell restoration during initial antiretroviral therapy. AIDS 32:2517-2524
AIDS-defining Cancer Project Working Group of IeDEA, COHERE in EuroCoord (2018) Non-Hodgkin lymphoma risk in adults living with HIV across five continents. AIDS 32:2777-2786
Mbonye, Uri; Wang, Benlian; Gokulrangan, Giridharan et al. (2018) Cyclin-dependent kinase 7 (CDK7)-mediated phosphorylation of the CDK9 activation loop promotes P-TEFb assembly with Tat and proviral HIV reactivation. J Biol Chem 293:10009-10025
Sayin, Ismail; Radtke, Andrea J; Vella, Laura A et al. (2018) Spatial distribution and function of T follicular regulatory cells in human lymph nodes. J Exp Med 215:1531-1542

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