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
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
Paparisto, Ermela; Woods, Matthew W; Coleman, Macon D et al. (2018) Evolution-Guided Structural and Functional Analyses of the HERC Family Reveal an Ancient Marine Origin and Determinants of Antiviral Activity. J Virol 92:
Llewellyn, George N; Alvarez-Carbonell, David; Chateau, Morgan et al. (2018) HIV-1 infection of microglial cells in a reconstituted humanized mouse model and identification of compounds that selectively reverse HIV latency. J Neurovirol 24:192-203
Longenecker, Chris T; Sullivan, Claire E; Morrison, Justin et al. (2018) The effects of HIV and smoking on aortic and splenic inflammation. AIDS 32:89-94
Tomas, Myreen E; Mana, Thriveen S C; Wilson, Brigid M et al. (2018) Tapering Courses of Oral Vancomycin Induce Persistent Disruption of the Microbiota That Provide Colonization Resistance to Clostridium difficile and Vancomycin-Resistant Enterococci in Mice. Antimicrob Agents Chemother 62:
Yanik, Elizabeth L; Hernández-Ramírez, Raúl U; Qin, Li et al. (2018) Brief Report: Cutaneous Melanoma Risk Among People With HIV in the United States and Canada. J Acquir Immune Defic Syndr 78:499-504
Sahmoudi, Karima; Abbassi, Hassan; Bouklata, Nada et al. (2018) Immune activation and regulatory T cells in Mycobacterium tuberculosis infected lymph nodes. BMC Immunol 19:33
Webel, Allison R; Moore, Shirley M; Longenecker, Chris T et al. (2018) Randomized Controlled Trial of the SystemCHANGE Intervention on Behaviors Related to Cardiovascular Risk in HIV+ Adults. J Acquir Immune Defic Syndr 78:23-33

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