The Tennessee CFAR, a four-way partnership between Vanderbilt University Medical Center, Meharry Medical College, Tennessee Department of Health, and Nashville CARES, focuses local resources and expertise on contemporary challenges to reduce the burden of HIV. Since the Tennessee CFAR was established in 2015, the Advanced Technologies Core (ATC, formerly called the Laboratory Sciences Core) has been integral to its success, providing scientific support and cutting-edge technologies to CFAR investigators.

Vanderbilt has a long visionary leadership history of prioritizing institutional support for shared core facilities and investing accordingly. The result is an impressive range of institutional cores equally available to Vanderbilt and Meharry investigators, including a state-of-the-art genomics core, VANTAGE (VANderbilt Technologies for Advanced Genomics; Simon Mallal Advanced Technologies Core Co-Director and VANTAGE Director). Over the current cycle, Dr. Kalams and the ATC staff, in collaboration with VANTAGE, have optimized workflows for preparing cells or tissues for genomics assays and analyzing complex data sets.

Meharry has also invested heavily in infrastructure and cutting-edge equipment during this grant cycle. This expands the repertoire of techniques and assays available to investigators at both institutions without duplicating resources available at Vanderbilt. The Meharry BSL3 laboratory underwent a comprehensive renovation with substantial equipment upgrades. The ATC at Meharry has expanded its services, including CRISPR gene editing and hematopoietic stem cell (HSC) culture expansion and differentiation.

Before 2015, many institutional resources were not available or routinely used by HIV investigators. As institutional cores serve all disciplines, their services are not tailored to meet needs specific to HIV researchers. The ATC has made great progress in bridging this gap by adapting and, in some cases, creating services and assays tailored to the research foci of our CFAR basic, clinical, and translational investigators using a highly effective “concierge” model. The concierge approach is based on the premise that CFAR laboratory offerings should be in response to scientific needs. For example, the ATC developed cell processing/isolation protocols for specific cell subsets from PBMCs, adipose tissue, skin, and vascular tissue to support growing immunology and comorbidities research programs engaging multiple CFAR investigators. The ATC has continued to develop assays to phenotype and evaluate the function of T and B lymphocytes, single-cell sort populations of rare cells, and analyze multi-parameter flow cytometry (fluorescence and mass cytometry) and single-cell RNA transcriptomic data. Through VANTAGE, the ATC has gained enhanced single cell capabilities, including B and T-cell receptor (BCR/TCR) sequencing, RNA transcriptional profiling, cellular indexing of transcriptomes and epitopes (CITEseq), HIV plasma RNA and proviral DNA sequencing, and integration site assays.

Aligned with the concierge approach to service offerings, the Advanced Technologies Core “continuum of support” model recognizes that complex laboratory technologies and the required bioinformatics expertise can present a high barrier to entry for ESI and investigators outside of the basic sciences. For example, the ATC may assist an investigator in determining which cells to analyze and in what numbers, designing the flow cytometry panel, sorting the cells, preparing for single-cell sequencing in VANTAGE, and performing analysis and data visualization to best address the scientific question. This end-to-end support has “lowered the bar” for CFAR investigators to apply cutting-edge technologies to their science – a capability completely lacking before the Advanced Technologies Core. During the next grant cycle, the ATC will continue to provide leadership and services specifically responsive to the needs of HIV investigators to help advance their science in ways not possible without CFAR. The Advanced Technologies Core​ will promote basic, clinical, and translational HIV research through three specific aims.

• Design and performance of HIV-focused flow cytometry assays including:
  • Expression of cell activation markers
  • Identification of memory T cell subsets and T regulatory cells
  • Intracellular cytokine expression
• Single cell sorting in a BSL2+ facility
• Single-cell transcriptomics
• T-cell receptor sequencing
• Mass cytometry (CyTOF)
• Sensitive PCR assays for HIV (Droplet digital PCR)
• HIV p24 ELISA
• Training of Core users
• Specimen processing and tracking
  • Plasma, PBMCs and other human specimen such as skin and adipose tissue
• DNA and/or RNA extraction from tissue

For service request or inquiries, please contact tn-cfar@vumc.org