Grantee Research Project Results
Vascular MAPs: Vascular and Neurovascular Tissue Models
EPA Grant Number: R835737C004Subproject: this is subproject number 004 , 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: Vascular MAPs: Vascular and Neurovascular Tissue Models
Investigators: Sheibani, Nader
Institution: 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:
A major objective of our research is to delineate the cell autonomous mechanisms that are responsible for adverse cellular dysfunction in response to various stress conditions, which contribute to neurovascular toxicity and tissue pathogenesis. To further delineate the role of cell-cell interactions and study of paracrine mechanisms which maintains the retinal neurovascular integrity, 3D organotypic models that represent the in vivo tissue architecture and organization are essential.
Approach:
Here we propose to develop an organotypic culture of neurovascular system using human induce pluripotent stem cells. These cells will be differentiated to various cellular component of the neurovasculature including endothelial cells, pericytes, and astrocytes. Using defined synthetic matrices, which allow for "biologically driven assembly" of these cells to a neurovascular unit, we will generate organotypic neurovascular culture systems. These cultures will be adapted for high throughput screening of chemicals with unknown toxicity to identify those with adverse effect on formation of capillary networks.
Expected Results:
Our hypothesis is that these compounds will have adverse effects on developmental processes, which depend on angiogenesis. Using our knowledge regarding the intracellular pathways that contribute to neurovascular dysfunction, we will utilize a high content automated imaging system for further analysis of hit compounds identified in a primary toxicity screen. This knowledge will advance our understanding of the cellular and molecular mechanisms and pathways which contribute to neurovascular dysfunction under adverse conditions, and better risk assessment and management of compounds with unknown toxic effects.
Publications and Presentations:
Publications have been submitted on this subproject: View all 21 publications for this subproject | View all 215 publications for this centerJournal Articles:
Journal Articles have been submitted on this subproject: View all 17 journal articles for this subproject | View all 81 journal articles for this centerSupplemental Keywords:
Capillary Morphogenesis, Oxidative Stress, Cellular Permeability, Inflammation, Inflammatory Mediators, Diabetic Retinopathy, Vascular Endothelial Growth Factor, Platelet Derived Growth Factor, MAPK PathwaysProgress and Final Reports:
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
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.
Project Research Results
17 journal articles for this subproject
Main Center: R835737
215 publications for this center
81 journal articles for this center