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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI096113-05
Application #
8874882
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
2017-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
5
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
White, Cory H; Beliakova-Bethell, Nadejda; Lada, Steven M et al. (2018) Transcriptional Modulation of Human Endogenous Retroviruses in Primary CD4+ T Cells Following Vorinostat Treatment. Front Immunol 9:603
Chaillon, Antoine; Gianella, Sara; Lada, Steven M et al. (2018) Size, Composition, and Evolution of HIV DNA Populations during Early Antiretroviral Therapy and Intensification with Maraviroc. J Virol 92:
Jiang, Guochun; Nguyen, Don; Archin, Nancie M et al. (2018) HIV latency is reversed by ACSS2-driven histone crotonylation. J Clin Invest 128:1190-1198
Dubé, Karine; Dee, Lynda; Evans, David et al. (2018) Perceptions of Equipoise, Risk-Benefit Ratios, and ""Otherwise Healthy Volunteers"" in the Context of Early-Phase HIV Cure Research in the United States: A Qualitative Inquiry. J Empir Res Hum Res Ethics 13:3-17
Prakash, Katya; Gianella, Sara; Dubé, Karine et al. (2018) Willingness to participate in HIV research at the end of life (EOL). PLoS One 13:e0199670
Papasavvas, Emmanouil; Lada, Steven M; Joseph, Jocelin et al. (2018) Analytical ART interruption does not irreversibly change pre-interruption levels of cellular HIV. AIDS :
Honeycutt, Jenna B; Liao, Baolin; Nixon, Christopher C et al. (2018) T cells establish and maintain CNS viral infection in HIV-infected humanized mice. J Clin Invest 128:2862-2876
Power, Jennifer; Westle, Andrew; Dowsett, Gary W et al. (2018) Perceptions of HIV cure research among people living with HIV in Australia. PLoS One 13:e0202647
Marsden, Matthew D; Wu, Xiaomeng; Navab, Sara M et al. (2018) Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents. Virology 520:83-93
Sung, Julia A; Sholtis, Katherine; Kirchherr, Jennifer et al. (2017) Vorinostat Renders the Replication-Competent Latent Reservoir of Human Immunodeficiency Virus (HIV) Vulnerable to Clearance by CD8 T Cells. EBioMedicine 23:52-58

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