Texas A&M Combinatorial Drug Discovery and High-throughput Flow Cytometry Core Facilities
Introduction
The Texas A&M Combinatorial Drug Discovery Program (CDDP) and High Throughput Flow Cytometry Program (HtFCP) are components of the Gulf Coast Consortia network of drug discovery core facilities offering academic and commercial users access to state-of-the-art high throughput biochemical and phenotypic screening services for single agent and combinatorial drug discovery research. Drug repurposing and drug combinations are therapeutics strategies of great interest to clinical cancer researchers. Repurposing is valuable for its potential to identify therapies that can be “fast tracked” into clinical applications without the long delays associated with New Drug Approvals. Drug combinations can be used in both a neoadjuvant setting as well as being a strategy to avoid or overcome drug resistance. High throughput library screening technologies that can be used to evaluate the therapeutic potential of large numbers of drugs, either as single agents or as drug combinations, are an effective way of accelerating the discovery of novel therapies for hard-to-treat cancers. The CDDP and the HtFCP provide sophisticated resources to support a wide range of cancer-related high-throughput library screening research applications. These core facilities provide cancer researchers with access to integrated library screening resources that include: 1) the technologic infrastructure to support high throughput biochemical and phenotypic screening research; 2) a data science infrastructure to critically evaluate experimental rigor and reproducibility as well as support downstream meta-analysis and data integration; and 3) a multi-disciplinary team of experts in pharmacology, immunology, high throughput drug discovery, imaging-based screening and analysis, flow cytometry, and data science. The CDDP and HtFCP are CFSA-supported multi-institutional core facilities providing researchers with access to these key resources.
Methods
The CDDP and HtFCP have specialized capabilities for supporting biochemical and phenotypic drug screening in a range of standard and bespoke 2D and 3D in vitro model systems including highly multiplexed monolayer cell cultures, spheroids and organoids, other ex vivo patient-derived cells, as well as radio-sensitizer screens. The HtFCP supports library screening in models involving non-adherent cancer cells including leukemias and MDS, screens for drug effects in heterotypic co-culture systems such as those useful for immunotherapy screening studies, and other single cell analytic technologies where the profiling of drug effects in heterogenous cell populations is important. The cores’ screening platforms include fully automated high throughput confocal and metabolic imaging, high-throughput flow cytometry, automated multi-modal biochemical endpoint detection systems, and a fully integrated and high-powered research x-ray irradiator well-suited for cell and tissue cultures and targeted irradiation of small animals. Data analysis services include both traditional statistical methods and advanced machine learning/AI technologies to contextualize pharmacologic, genomic, and transcriptomic interactions.
Results
The CDDP and HtFCP provide academic and commercial cancer researchers with access to compound/drug libraries, laboratory automation, specialized cell culture capabilities and imaging platforms, informatics, and the technical expertise necessary for library-screening studies using advanced cellular models of cancer. The cores are designed to provide “fit for purpose” high throughput cell-based and biochemical screening services to support the full spectrum of cancer-related drug discovery research.
Conclusion
The CDDP and HtFCP core facilities are dedicated to providing Texas’ cancer researchers with access to sophisticated high-throughput screening and data analysis services that are compatible with advanced cellular models of cancer combined a team of experts that deliver provide 1) project design and consultation; 2) assay design, development, optimization, and screening; and 3) data analysis, informatics, and documentation. The goal of these Programs is to support the discovery of novel single agent and combinatorial therapeutics that can be rapidly advanced to animal testing and clinical evaluation.