The main objective of the Genomics Core will be to provide access to researchers on the collaborator to genomics technologies and the bioinformatic analysis needed to analyze the complex data derived from such technologies. Genomics technologies have become essential laboratory tools and will generate data that will guide the research in the collaboratory towards an HIV-1 cure. The Genomics Core will interact with every project in every objective and with the other cores proposed in the collaboratory. Specifically, with respect to virus genomics, the Genomics Core will provide access to sequencing, which will be used to identify the defects in proviral DNA that result in non-competent virus (Project 4.1) and will also be used to identify additional virus reservoirs by revealing viruses in the plasma whose sequence does not correlate with virus derived from the well-characterized CD4+ T cell reservoir (Project 4.2). Additionally, each project will benefit from the assays at the Genomics Core to monitor HIV replication in order to evaluate latency and the effects of HlV-inducing compounds. In respect to host genomics, the Genomics Core will primarily provide gene expression assays (whole genome microarray and qRT-PCR) in order to define the molecular mechanisms underlying viral persistence (Projects 1.1, 1.2,1.4 and 1.5) and determine biomarkers indicative of effective HlV-inducing compounds (Project 2.1). In addition, chromatin immunoprecipitation (ChIP) coupled with high throughput sequencing (ChlP-Seq) will be used to investigate gene regulation by the BAF chromatin remodeling complex (Project 1.2). When these studies are complete the genomics assays provided by the Genomics Core will have provided a better understanding of HIV latency, identified new pathways and avenues for therapeutic intervention, delineated the mode of action of HlV-inducing compounds, and characterized new viral reservoir in HIV-infected individuals.
The experiments performed at the Genomics Core will use the latest technologies for analyzing virus and host genomes. The results of these experiments will accelerate research towards a cure for HIV-1.
|Honeycutt, Jenna B; Sheridan, Patricia A; Matsushima, Glenn K et al. (2015) Humanized mouse models for HIV-1 infection of the CNS. J Neurovirol 21:301-9|
|King, Helen L; Keller, Samuel B; Giancola, Michael A et al. (2014) Pre-exposure prophylaxis accessibility research and evaluation (PrEPARE Study). AIDS Behav 18:1722-5|
|Manson McManamy, Mary E; Hakre, Shweta; Verdin, Eric M et al. (2014) Therapy for latent HIV-1 infection: the role of histone deacetylase inhibitors. Antivir Chem Chemother 23:145-9|
|Spivak, Adam M; Andrade, Adriana; Eisele, Evelyn et al. (2014) A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy. Clin Infect Dis 58:883-90|
|Duverger, Alexandra; Wolschendorf, Frank; Anderson, Joshua C et al. (2014) Kinase control of latent HIV-1 infection: PIM-1 kinase as a major contributor to HIV-1 reactivation. J Virol 88:364-76|
|Denton, Paul W; Long, Julie M; Wietgrefe, Stephen W et al. (2014) Targeted cytotoxic therapy kills persisting HIV infected cells during ART. PLoS Pathog 10:e1003872|
|Abreu, Celina M; Price, Sarah L; Shirk, Erin N et al. (2014) Dual role of novel ingenol derivatives from Euphorbia tirucalli in HIV replication: inhibition of de novo infection and activation of viral LTR. PLoS One 9:e97257|
|Archin, Nancie M; Margolis, David M (2014) Emerging strategies to deplete the HIV reservoir. Curr Opin Infect Dis 27:29-35|
|Liu, Pingyang; Xiang, Yanhui; Fujinaga, Koh et al. (2014) Release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein (snRNP) activates hexamethylene bisacetamide-inducible protein (HEXIM1) transcription. J Biol Chem 289:9918-25|
|Persaud, Deborah; Patel, Kunjal; Karalius, Brad et al. (2014) Influence of age at virologic control on peripheral blood human immunodeficiency virus reservoir size and serostatus in perinatally infected adolescents. JAMA Pediatr 168:1138-46|
Showing the most recent 10 out of 77 publications