Robust assembly of human tissues for disease modeling and discovery
Forward BIO Institute’s Director Bill Murphy recently gave the Plenary talk, entitled Robust Assembly of Human Tissues for Disease Modeling and Discovery, at the Society of Toxicology 2019 Annual Meeting in Baltimore, MD.
The need for human, organotypic culture models coupled with the requirements of contemporary drug discovery and toxin screening (i.e. reproducibility, high throughput, transferability of data, clear mechanisms of action) frame an opportunity for a paradigm shift. The next generation of high throughput cell-based assay formats will require a broadly applicable set of tools for human tissue assembly and analysis. Toward that end, we have recently focused on (1) generating iPS-derived cells that properly represent the diverse phenotypic characteristics of developing or mature human somatic cells, (2) assembling organotypic cell culture systems that are robust and reproducible, (3) translating organotypic cell culture models to microscale systems for high-throughput screening, and (4) combining genomic analyses with bioinformatics to gain insights into organotypic model assembly and the pathways influenced by drugs and toxins. This lecture will emphasize recent studies in which we have explored assembly of organotypic vascular, liver, and brain tissues. These tissues mimic critical aspects of human organ structure and can be used for reproducible identification of drug candidates and toxic compounds. Our work particularly emphasizes reproducibility and data transferability, which we view as vital to the widespread use of organotypic human models in toxicity testing. The lecture will also introduce the use of our assembled human tissues to develop models of rare developmental disorders and degenerative diseases of the brain.