Welcome to the Human Models for Analysis of Pathways (HMAPs) Center
The Human Models for Analysis of Pathways (HMAPs) Center, is an EPA sponsored Science to Achieve Results (STAR) center, based in University of Wisconsin Madison, that addresses the need for human, organotypic culture models (/ micro-physiological systems / human tissue on a chip) that comply with the requirements of contemporary toxin screening and drug discovery (i.e. reproducibility, high throughput, transferability of data, clear mechanisms of action, defined adverse outcomes).
These technologies will provide a suitable alternative and reduce the number of animals required for in vivo studies reducing the overreliance on animal studies. Current in vivo animal models do not capture the biological diversity and complexity of human tissues and it is not possible to screen the tens of thousands of compounds that are present in our environment in animal models. Similarly, there is a need for human models to validate drug efficacy and avoid drug induced toxicity, as greater than 90% of new drug candidates fail even after passing through the majority of the drug development pipeline.
The H-MAPs Center is committed to transforming chemical toxicity testing and drug discovery by taking advantage of advances in biology, biotechnology, and computer modeling. The overall objective of the center is to create transformative organotypic human models in formats that offer unique practical capabilities for toxin screening and pathway analysis.
The Human MAPs Center Objectives are to:
- Generate human pluripotent stem cell-derived cells that properly represent the diverse phenotypic characteristics of developing or mature human somatic cells;
- Generate organotypic cell culture models that are robust and reproducible;
- Translate organotypic cell culture models to microscale systems for HTS;
- Combine genomic/epigenomic analyses with bioinformatics to gain molecular level insights into organotypic model assembly and the pathways influenced by toxins.
The H-MAPs Center brings together leading experts in human pluripotent stem cell biology, human development, and microscale tissue engineering to develop organotypic human models. The Center will also form organotypic human models in robust, innovative high throughput screening systems and identify mechanisms of action associated with toxicity using bioinformatics-based pathway analysis.
Innovative Technology Cores
The HMAPs Center activities are supported by three Innovative Technology Cores (ITCs). The Synthetic Matrices ITC provides defined synthetic hydrogels, thin films and synthetic microparticles for use across center projects. These matrices provide the building blocks for the biologically driven assembly in the organotypic culture models being generated in the HMAPs Center. The Microscale Systems ITC provides innovative microfluidic technologies that can transform the organotypic culture models from standard assay formats to high throughput screening formats. The Pathway Analysis ITC provides the ability to identify which specific cell phenotypes are influenced by a drug or toxin, and identifies which gene regulatory networks are affected by the compound exposure. Forming the human tissues in a dish offers the potential to capture the complexity associated with human tissue development and function. However, the increased complexity and phenotypic diversity in organotypic models makes it difficult to understand which cell types a toxin is affecting, and by which specific signaling mechanisms. Bioinformatics and computational tools are required to extract mechanistic information. This Core provides the full suite of bioinformatics tools needed to support the H-MAPs Center objectives.
Nature Biomedical Engineering article co-written by Dr. Nguyen and Dr. Daly demonstrate a synthetic alternative to matrigel for stem cell expansion and vascular screening
Since highly versatile human stem cells were discovered at the University of Wisconsin-Madison nearly 20 years ago, their path to the market and clinic has been slowed by a range of complications. Both embryonic stem cells and …August 16, 2017
Human MAP Center Researchers Present at the Horizons and Challenges in Organotypic Culture Models for Predictive Toxicology Satellite Meeting
On Saturday the 11th of March 2017 at the Horizons and Challenges in Organotypic Culture Models for Predictive Toxicology Satellite Meeting in Baltimore, the Human Models for Analysis of Pathways (HMAPs) Center presented on emerging …March 12, 2017
HMAP Center researchers Ms. Molly Morgan (graduate student) and Dr. Brian Johnson (postdoctoral researcher) from Cancer MAPs project win Peta Prize for Newly developed Adverse Outcome Pathway.January 15, 2017
HMAP Researcher Dr. Eric Nguyen wins Walsh Research Travel Award to Society of Toxicology conference
Postdoctoral researcher Dr. Eric Nguyen from Vascular MAPs project wins $1000 Walsh Research Travel Award from the McPherson Eye Institute for the upcoming Society Of Toxicology conference in Baltimore, Maryland in March 2017. Dr. Nguyen will …October 10, 2016
Prof. Randolph Ashton who is leading efforts in the Brain MAP project of the Human MAP Center was awarded the Young Investigator Faculty Award by the Hilton Head Regenerative Medicine Workshop. The award was given …February 26, 2016
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