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Real Time Elucidation of Drug-Drug Interactions via Dual Reporter Cell Technology and Microfabricated Arrays

通过双报告细胞技术和微加工阵列实时阐明药物间相互作用

基本信息

批准号：
9767130
负责人：
Mehmet Toner
金额：
$ 45.08万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-30 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9767130
关键词：
Activation Analysis Address Affect American Assessment tool Biology CAR receptor Cell Culture Techniques Cells Clinic Clinical Trials Coculture Techniques Communities Complex Data Data Set Development Dimensions Drug Exposure Drug Interactions Environment Enzymes Event Exposure to Fluorescence Focus Groups Future Genetic Transcription Goals Hepatocyte Human In Vitro Inflammation Inflammatory Injury Kupffer Cells Lead Lentivirus Infections Lentivirus Vector Libraries Liver Metabolism Microfabrication Modeling Molecular Pathogenesis Patient Representative Patients Personal Satisfaction Pharmaceutical Preparations Phase Physiological Physiology Play Public Health Reporter Reporting Research Resources Response Elements Role Signal Transduction Source Stimulus Subfamily lentivirinae System Technology Testing Time Time Study Tissue Engineering Tissues Toxic effect Transcriptional Activation Transcriptional Regulation Translating Universities Work adverse event risk constitutive androstane receptor culture plates design design and construction drug discovery drug metabolism drug testing enzyme activity experimental study genetic regulatory protein high throughput analysis improved in vivo induced pluripotent stem cell intercellular communication particle patient safety pre-clinical pregnane X receptor prevent promoter response stem therapeutic development tool transcription factor

项目摘要

With the number of Americans who take more than one drug for their well-being increasing, there is an increasing risk of adverse events due to drug-drug interactions. New tools are necessary to understand biology at the initiation of the drug metabolic process, i.e., transcriptional regulation. Since multiple enzymes may act on a given drug, and multiple transcription factors may activate an enzyme, the problem becomes quite complex. In addition, new in vitro tissue engineered models that recapitulate the human physiology are required to get an accurate approximation for the in vivo response of drugs. We propose to extend out microphysiological in vitro liver model to a liver-on-a-chip array to study in high-throughput the transcriptional activity of enzymes and apply it to the study of drug-drug interactions (DDIs). Our tissue engineered construct will use both primary human cells and induced pluripotent stem cells (iPSC)-derived cells. This project will be carried out by distinct research groups. The PIs have a very strong collaborative record of accomplishment. Dr. Martin Yarmush (MGH) will oversee tissue engineering of the liver-on-a-chip and the drug interaction studies. Dr. Mehmet Toner, Director of the BioMEMs Resource Center at MGH, will lead the microfabrication group focusing on the development of microfabricated array. The iPSC-derived cells will be sourced from Dr. Yoon Y Jang at Johns Hopkins University.

随着服用一种以上药物的美国人越来越多，