CDSI Research Technologies
Clinical/Phenotyping
- Clinical phenotyping core of cryopreserved PBMCs, tissue (skin), blister fluid, DNA/RNA from well defined DHS phenotypes
- HLA matched drug tolerant controls/study volunteers
- BioVu (DNA/Plasma)
- International collaborations
Cellular
- ELISpot, Flow cytometry
- Cell sorting/cell lines
- Tetramer technology, T-cell cloning
- TCR reporter assays/Tscan
- Skin technologies from acute, patch test positive and recovery phase samples
Molecular
- Deep sequencing (HLA/TCR)
- Single cell sequencing
- Single cell transcriptomics
- IMGSCT Core
- VANTAGE Core
- Automation
Data management/analysis
- VGAS – Genomics and T cell visualization capacity
- eLAB – Laboratory management
- Labguru – Data and project management
- REDCap – Clinical data management
- REDBRIcs (home-grown lab information management system)
Teambuilding and leadership
Collaborations
- Proteomics (Peptide binding/elution)
- Virtual screening
- Phenome-wide association studies
- Expression quantitative trait loci
- HLA & KIR imputation
- T-cell cloning
- Herpesvirology
- Biophotonics/imaging
- Tissue engineering
- IgE hybridoma
- Clinical trials
- Preclinical drug screening
Education and Training
- Clinicians
- Junior faculty mentorship
- Post-doctoral
- Pre-graduate
- Undergraduate
- Technicians
- Government/regulatory/industry
Innovative Approaches and Technologies
Specimens collected at different time points from consenting patients provide invaluable starting material for a variety of laboratory studies. These specimens are used for diagnostic purposes, to assign genotype/phenotype and to carry out experiments aimed at understanding the immunopathology and cellular mechanisms involved in adverse reactions.
Single-cell sequence analysis of individual patient samples taken from reaction sites can provide profiles of RNA transcriptomes, T cell receptors that have been engaged and surface markers of other cells that may be implicated in disease. Results from these analyses can inform future experiments at a patient specific level.
Identification of HLA profiles and dominant TCRs at sites of tissue damage via single cell studies allows for the creation of patient specific in vitro environments. Various samples are collected from patients during the acute phase of disease. Blister fluid samples can be used to identify dominant T cell receptors (TCR) at sites of tissue damage while saliva samples are used to determine the human leukocyte antigen (HLA) profile of each patient. This information can then be used in additional in vitro experiments to determine HLA restriction in each patient.
Defining HLA risk alleles associated with SCAR in a drug specific manner can improve prevention efforts and drug safety across diverse patient populations. Successful pharmacogenomic screening is dependent upon the development of simple, robust, cost-effective testing that can be implemented in routine diagnostic laboratories.
CDSI previously identified an association between the development of Vancomycin-induced DRESS and HLA-A*32:01. In order to identify patients at risk of developing an adverse reaction, a rapid allele test for HLA-A*32:01 was developed and can be used in the clinical setting as a pre-prescription assessment.
Discovery of Key Genetic Risk factors for Severe Drug-induced diseases such as Abacavir Hypersensitivity, Drug Reactions and Eosinophilia and Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
CDSI collaborator Eric Tkaczyk, MD, PhD, is a physician-scientist with research interests in biophotonics for diagnosis and treatment of skin diseases.
He is the founding director of the Vanderbilt Dermatology Translational Research Clinic (VDTRC), and he lectures internationally on dermatologic imaging technologies, which is his research focus.
Fundamental Technology Research
- Noninvasive imaging of human leukocyte dynamics
Clinical Translational Research
- 3D, colorimetric, and hyperspectral imaging of rashes
- Artificial intelligence and crowd sourcing for photo analysis
- Skin biomechanical measurements in sclerosing disease
