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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Center Core Grants (P30)
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Special Emphasis Panel (ZAI1)
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Beaubien, Candice M
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Case Western Reserve University
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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
Elion, Richard A; Althoff, Keri N; Zhang, Jinbing et al. (2018) Recent Abacavir Use Increases Risk of Type 1 and Type 2 Myocardial Infarctions Among Adults With HIV. J Acquir Immune Defic Syndr 78:62-72
Martinez, Leonardo; Shen, Ye; Handel, Andreas et al. (2018) Effectiveness of WHO's pragmatic screening algorithm for child contacts of tuberculosis cases in resource-constrained settings: a prospective cohort study in Uganda. Lancet Respir Med 6:276-286
Grover, Surbhi; Desir, Fidel; Jing, Yuezhou et al. (2018) Reduced Cancer Survival Among Adults With HIV and AIDS-Defining Illnesses Despite No Difference in Cancer Stage at Diagnosis. J Acquir Immune Defic Syndr 79:421-429
Kityo, Cissy; Makamdop, Krystelle Nganou; Rothenberger, Meghan et al. (2018) Lymphoid tissue fibrosis is associated with impaired vaccine responses. J Clin Invest 128:2763-2773
Wiredja, Danica D; Tabler, Caroline O; Schlatzer, Daniela M et al. (2018) Global phosphoproteomics of CCR5-tropic HIV-1 signaling reveals reprogramming of cellular protein production pathways and identifies p70-S6K1 and MK2 as HIV-responsive kinases required for optimal infection of CD4+ T cells. Retrovirology 15:44
Oliveira, Vitor H F; Perazzo, Joseph D; Josephson, Richard A et al. (2018) Association Between the 6-Minute Walk Test Distance and Peak Cardiorespiratory Fitness Among People Living with HIV Varies by Fitness Level. J Assoc Nurses AIDS Care 29:775-781

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