Novel and Integrated Intestine-liver Crosstalk on Hepatic Xenobiotic Metabolism
Thursday April 29, 2021
10:00 am
-
11:30 am
Eastern Time (ET)
View session on the EB Virtual Platform (EB registration required)
DMDD
TOX
Chair :
Grace Guo
Rutgers Univ - Ernest Mario Sch of Pharmacology
Hongbing Wang
University of Maryland
The liver stays in the center of drug metabolism that is regulated by xenobiotic receptors and endocrine factors during development, physiology and pathology. The intestine and liver are closely interacted and a role of intestine derived factors is emerging in critically regulating the endobiotic and xenobiotic metabolism in the liver. Novel medicine or technologies to treat human diseases will be developed inspired by these interactions. This symposium will bring the best knowledge, novel in vitro and in vivo technology, and application of intestine-liver crosstalk to audience with interest in novel drug development and pharmacology.
Speakers
Shiew-Mei Huang
- US Food and Drug Administration
Emerging Role of Organ-on-a-Chip Technologies in Quantitative Clinical Pharmacology Evaluation
The three-dimensional (3D) cell culture models present physiologically relevant cellular microenvironment and offer great promise for assessing drug disposition and pharmacokinetics that influence drug safety and efficacy at an early stage of drug development. Currently, there are numerous different types of 3D culture systems for liver and gut, from simple spheroids to more complicated organs-on-chips and from single-cell type static 3D models to cell-coculture 3D models equipped with microfluidic flow control.
Andrew Patterson
- Penn State University
Nuclear Receptors as Moderators of Host-Microbiome Communication
Nuclear receptors are important components of the host-microbiota communication network. Metabolomics and sequencing-based microbial community profiling, two recent technological advances, have helped to solidify this host-microbiota signaling concept and identified not only how specific ligands generated by the host and by the microbiota can modulate nuclear receptor activity, but also how activation/disruption of these pathways can influence and shape the microbiota.
Julia Yue Cui
- University of Washington
Reprogramming the Gut-liver Axis During Early Life Toxicant Exposure
Developmental exposure to environmental toxicants has been frequently linked to delayed onset of complex human diseases later in life. This talk will discuss how Developmental reprogramming the gut microbiome may contribute to the persistent toxicities of the host in adulthood, using the gut-liver axis as an example.
Murat Cirit
- Javelin Biotech
Integrated Gut and Liver Microphysiological Systems for Quantitative In Vitro Pharmacokinetic Studies
Design of successful clinical trials requires accurate preclinical assessment of drug candidate’s pharmacokinetic, pharmacodynamic and toxicity profiles. However, due to translational gap between human physiology and and existing preclinical models including both in vitro culture and animal models, a large percentage of drug candidates fail at the clinical trial stage due to a lack of efficacy and unacceptable toxicity. This need for more human-physiology relevant in vitro systems for preclinical testing has led to a major effort to develop “Microphysiological Systems (MPS)” based on engineered human tissue constructs. Javelin Biotech bridges this gap by merging human MPS technologies and quantitative systems pharmacology to predict drug human clinical pharmacokinetic profiles during preclinical studies.
Guo Zhong
- University of Washington
Postnatal Loss of Cyp26a1 and Cyp26b1 in Mice Causes Impaired Retinoid Homeostasis in Multiple Organs
Talk description coming soon!