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: Human Models for Analysis of Pathways (H–MAPs) Center
Center Director: Murphy, William L
Title: Liver MAPs
Investigators: Thomson, James
Institution: The Morgridge Institute for Research
EPA Project Officer: Klieforth, Barbara I
Project Period: December 1, 2014 through November 30, 2018
Project Amount: Refer to main center abstract for funding details.
RFA: Organotypic Culture Models for Predictive Toxicology Center (2013) RFA Text |  Recipients Lists
Research Category: Safer Chemicals , Health , Human Health

Objective:

The specific objectives are to: 

  1. Identify regulatory networks that control liver maturation.
  2. Screen for factors that promote human ES/iPS cell-derived hepatocyte maturation. 
  3. 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. 

Supplemental Keywords:

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

Progress and Final Reports:

2015 Progress Report
2016 Progress Report


Main Center Abstract and Reports:

R835737    Human Models for Analysis of Pathways (H–MAPs) Center

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