Ex vivo studies applying high throughput and novel genetic, immunologic, and bioinformatics approaches to clinical samples allow detailed investigation of novel and known pathways.
Comparison of Immune Cell Phenotypes from Lymph Node Aspirates from HIV+ Controllers and HIV+ ART-Suppressed Non-Controllers
Lymph nodes are a major anatomical HIV reservoir. During chronic HIV infection, virus mainly persists in follicles (vs. T cell zone). One approach towards achieving a “functional cure” for HIV is to maximize the host’s immune response to closely recapitulate that of HIV-infected individuals who maintain viral and immune control in the absence of therapy (HIV long-term non-progressors). For this project we will collect longitudinal lymph node fine needle aspirates from HIV “elite” controllers, individuals who can suppress virus in the absence of therapy, to determine potential novel mechanisms of HIV control relevant to HIV cure strategies. In collaboration with Dr. Nadia Roan’s lab at UCSF, we will be performing single cell RNA and antibody sequencing as well as high-dimensional cytometry time of flight (CyTOF) to identify key gene and antibody expression from individual immune cells.
Changes in Gene Expression Related to Interleukin 1-Beta Signaling.
Even with advances in HIV antiretroviral therapy (ART), individuals with HIV experience higher rates of aging-associated diseases and death compared to individuals without HIV. HIV is suppressed but not fully eradicated with HIV treatment, and thus, residual inflammation may persist for years, leading to increased risk of cardiovascular disease, stroke, cancer, and death. Interleukin-1 beta (IL-1β) plays a critical role in reducing systemic inflammation and cardiovascular events in the general population and in maintaining the HIV “reservoir” in treated HIV individuals. In collaboration with Dr. Rafick Sekaly’s lab at Case Western University, we will use advanced sequencing methods to identify genes and immunologic pathways that mediate IL-1β signaling. We will use blood samples from a recent phase I study of canakinumab (anti-IL-1β monoclonal antibody) in HIV+ ART-suppressed individuals, led by Dr. Priscilla Hsue at UCSF. Results from this study may identify novel therapeutic targets that may be broadly applicable for the treatment of inflammation-associated diseases in HIV+ and non-HIV populations.
