Note: Beginning with Fall 2016, The Basic Science program has been combined into the Mentored Scientist Award mechanism - which now has three scientific priority areas for funding: Basic Science, Clinical/ Translational/ Epidemiological/ Behavioral, and Implementation Science.
Below are the awards made under the Basic Science program from 1994 to 2016.
58 Awards
-
Cytokine Responses in Elite Controllers of HIV
Cytokine Responses in Elite Controllers of HIV
Abstract
There remains a subset of HIV-infected patients who maintain undetectable plasma HIV RNA levels (elite controllers) that make up approximately 1% of the HIV-infected population. The mechanism for this unique status is the subject of intensive research, but remains unknown. The objective of this proposal is to determine how a set of six cytokines found to be elevated in the serum of HIV elite controllers influences viral replication and cellular activation.
-
The Anti-HIV mechanism of human Piwil2
The Anti-HIV mechanism of human Piwil2
Abstract
As an obligatory intracellular parasite with limited genome size, retroviruses interact with both supportive and inhibitory host factors to complete their life cycle. Inhibitory factors could, in principle, intervene against the virus at every step of replication and are collectively called host restriction factors. Preliminary data indicated that human Piwil2 inhibited HIV replication at the step of HIV protein synthesis. Our objective is to understand the anti-HIV mechanism of Piwil2 and evaluate its physiological roles in cells or tissues with high levels of Piwil2.
-
Investigating the interface between HIV-1 proteins and the host cellular ubiquitin machinery
Investigating the interface between HIV-1 proteins and the host cellular ubiquitin machinery
Abstract
HIV relies heavily on remodeling host regulatory networks for its replication. One major target of this remodeling process is the cellular ubiquitin machinery, which modifies proteins by adding ubiquitin moieties to target them for degradation and to modulate their activities. HIV exploits the ubiquitination system as a means to interfere with crucial antiviral pathways and immune mechanisms. Therefore, targeting interactions between HIV proteins and the human ubiquitin machinery is a promising direction for developing new anti-HIV therapeutics.
-
Intrapatient Coevolution Between the Antibody Repertoire and HIV Populations
Intrapatient Coevolution Between the Antibody Repertoire and HIV Populations
Abstract
The antibody repertoire (AbR) is a component of the adaptive immune system that is capable of undergoing real-time coevolution with infectious pathogens. I aim to characterize the genetic interaction that takes place between the AbR and HIV over the course of acute infection and to infer coevolutionary genetic signatures to detect the specific loci engaged in this interaction. My approach has the potential to provide a systems level view of all AbR/HIV interacting sites and will illuminate how these interactions change over time.
-
Mechanisms Underlying CD4 T-Cell Depletion and Inflammation During Aids Progression
Mechanisms Underlying CD4 T-Cell Depletion and Inflammation During Aids Progression
Abstract
The depletion of CD4 T cells and development of chronic inflammation represent signature pathological processes centrally contributing to clinical progression of HIV disease. Current therapy chiefly diminishes viral replication. Novel therapeutics preventing CD4 T-cell depletion and/or reducing chronic inflammation could form valuable adjuncts to antiviral medications potentially improving long-term clinical outcomes including limiting the early appearance of diseases associated with aging. Our studies suggest that these signature processes are, in fact, interrelated.
-
Exploring the Role of Caspase-1-Mediated-Pyroptosis in Promoting Chronic Inflammation in HIV Patients
Exploring the Role of Caspase-1-Mediated-Pyroptosis in Promoting Chronic Inflammation in HIV Patients
Abstract
The depletion of CD4 T cells and the development of chronic inflammation are signature processes in HIV pathogenesis that propel progression to AIDS. Our recent ex vivo studies have revealed how most lymphoid CD4 T cells die by caspase-1-mediated-pyroptosis, an intensely inflammatory form of programmed cell death, providing an unexpected association between these two disease-promoting processes.
-
Mucosal Natural Killer T (NKT) cells and the Gut Microbiome in HIV-1 Infection
Mucosal Natural Killer T (NKT) cells and the Gut Microbiome in HIV-1 Infection
Abstract
Invariant natural killer T (NKT) cells are innate-like T cells that respond to lipid antigens presented on the MHC class I-like molecule CD1d. These immunoregulatory cells have the capacity for abundant cytokine release almost immediately after antigen recognition and are essential for the activation of multiple arms of the immune response, including dendritic cells, conventional T cells and B cells. Murine studies have shown that the intestinal microbiome is an important factor in the maturation of functional NKT cells.
-
Mechanistic and Phenotypic Characterization of Semen Amyloid Disassembler as Novel Approach to HIV Microbicide Development
Mechanistic and Phenotypic Characterization of Semen Amyloid Disassembler as Novel Approach to HIV Microbicide Development
Abstract
The continuing spread of HIV/AIDS in people is predominantly fueled by sexual exposure to HIV-contaminated semen/seminal plasma (SP). SP harbors HIV infectivity enhancing factors that include at least two major classes of naturally occurring amyloid fibrils that promote virion attachment to cellular targets. SP also harbors a variety of pro-inflammatory factors that can indirectly facilitate HIV transmission by promoting the production of cytokines/chemokines that recruit permissive cells, enhance the translocation of HIV across the genital epithelium, and activate HIV gene transcription.