Grantee Research Project Results

Liver MAPs

EPA Grant Number: R835737C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R835737
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: The Morgridge Institute for Research
Center Director: Thomson, James
Title: Liver MAPs
Investigators: Thomson, James
Institution: The Morgridge Institute for Research
Current Institution: The Morgridge Institute for Research , University of Wisconsin - Madison
EPA Project Officer: Aja, Hayley
Project Period: December 1, 2014 through November 30, 2018 (Extended to November 30, 2019)
RFA: Organotypic Culture Models for Predictive Toxicology Center (2013) RFA Text | Recipients Lists
Research Category: Chemical Safety for Sustainability

Objective:

The specific objectives are to:

Identify regulatory networks that control liver maturation.
Screen for factors that promote human ES/iPS cell-derived hepatocyte maturation.
Optimize 3D organotypic cultures of human ES cell-derived hepatocytes with mature metabolic function.

Approach:

We will use state of the art genomic and epigenomic tools to identify regulatory networks that control liver maturation, perform robotic screens of factors that interact with those pathways to promote human ES/iPS cell-derived hepatocyte maturation, and use the identified factors to optimize 3D organotypic cultures of human ES cell-derived hepatocytes with mature metabolic function.

Expected Results:

The major outcome of this project will be to produce functionally mature ES/iPS cell-derived hepatocytes in 3D organotypic cultures broadly useful in toxicological studies. However, maturation of all human ES/iPS cell derivatives is a central challenge for the field. We anticipate that the epigenetic analysis in this project will yield basic principles for understanding maturation relevant to other tissues, and thus should facilitate even wider use of human ES/iPS cell-derivatives in toxicological studies.

Publications and Presentations:

Publications have been submitted on this subproject: View all 8 publications for this subproject | View all 215 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 4 journal articles for this subproject | View all 81 journal articles for this center

Supplemental Keywords:

Hepatoxicity, liver metabolism, toxicology, drug development, high throughput screening, combinatorial screening, phenotypic screening, microphysiological system

Progress and Final Reports:

Main Center Abstract and Reports:

R835737 The Morgridge Institute for Research

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R835737C001 Liver MAPs
R835737C002 Brain MAPs
R835737C003 Cancer MAPs: A 3D Organotypic Microfluidic Culture System to Identify Chemicals that Impact Progression and Development of Breast Cancer
R835737C004 Vascular MAPs: Vascular and Neurovascular Tissue Models
R835737C005 Pathway Analysis Core

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.