Brain MAPsEPA Grant Number: R835737C002
Subproject: this is subproject number 002 , 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: Brain MAPs
Investigators: Ashton, Randolph S
Institution: University of Wisconsin Madison
EPA Project Officer: Klieforth, Barbara I
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: Safer Chemicals , Health , Human Health
The proposed project will generate a high throughput neurotoxicity screening platform that recapitulates the phenotypic diversity within the human central nervous system (hCNS) while still being sensitive enough to detect toxicity towards a single phenotype.
Novel differentiation protocols and innovative microfabrication techniques will be used to generate a microfluidic screening platform comprised of an array of 3D organotypic tissues derived from human pluripotent stem cells and differentiated into region-specific tissues that span the hCNS.
Collectively, we hypothesize that the tissues will capture an unparalleled amount of hCNS phenotypic diversity, and their development will be modeled using RNA-seq analysis to comprehensively capture this diversity and provide fundamental insights into signaling pathways that govern their development, function, and can potentially be targeted by toxins. Furthermore, we will use Cas9-mediated genome editing to increase the versatility of our organotypic hCNS model. In combination with high-content imaging, our microfluidic screening platform will be ideal for executing quantitative high throughput screening assays to generate predictive dose-response data on toxins with neural phenotype-specific effects.
Publications and Presentations:Publications have been submitted on this subproject: View all 10 publications for this subproject | View all 198 publications for this center
Journal Articles:Journal Articles have been submitted on this subproject: View all 4 journal articles for this subproject | View all 64 journal articles for this center
Supplemental Keywords:Hox genes and transcription factors, neural stem cells, Paraquat, and dopaminergic neurons
Progress 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