Overview

The overall goal of the Indiana University Microphysiological systems for Alzheimer’s Disease (MPS-AD) Center is to develop human induced pluripotent stem cell (iPSC)-based 3D models as reproducible and scalable platforms to enable the effective study of Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD), as well as to implement these models as platforms for drug discovery.
AD is a leading cause of dementia worldwide. While the core pathologies of AD are β-amyloid (Aβ) extracellular plaques and aggregation of hyperphosphorylated tau (pTau) within neurofibrillary tangles (NFTs), AD is also associated with many accompanying pathologies including inflammation, increased activation of microglia and astrocytes, dysfunction of vasculature, as well as synaptic and neuronal loss. More recent genome-wide association studies (GWAS) for sporadic late-onset AD (LOAD) point to a significant role for glial cells, especially microglia, as well as vascular cells including endothelial cells, astrocytes and pericytes. Understanding the biological pathways underlying AD therefore requires a deeper analysis of the dysfunction of all the cell types in the microenvironment. iPSCs have provided unprecedented access to the investigation of cellular pathologies associated with AD/ADRD, owing to their human cellular origin and the ability to direct their differentiation into any desired cell type associated with the disease state.  However, studies to date using iPSCs for studies of AD/ADRD have often focused on individual cell types, used simplistic co-cultures, often lacked rigor, reproducibility and standardization, and showed high variability in outcome measures.  
We are developing and optimizing 3D MPS models that consist of multiple types of cells to mimic physiological aspects of AD/ADRD using the most rigorous and reproducible protocols. We are also conducting drug discovery studies. Lastly, we are working to make these 3D MPS models and their associated data available to the AD/ADRD research community.  

Neurons

Astrocytes

Microglia

Research Goals

Goal 1

To explore specific iPSCs representing critical features of AD/ADRD pathophysiology for the generation of MPS models.

Goal 2

To engineer and characterize robust, reproducible, and standardized brain organoid MPS models that faithfully recapitulate key features of human AD/ADRD pathophysiology.

Goal 3

To optimize and standardize MPS models for preclinical efficacy and safety using pharmacodynamic (PD)/pharmacokinetic (PK) approaches.

Goal 4

To facilitate and enable implementation of our MPS models by the research community by sharing datasets, biosamples, protocols, and research tools.

Leadership

Name Role Affiliation
Jason Meyer, PhD Lead PI Indiana University School of Medicine
Bruce Lamb, PhD MPI Indiana University School of Medicine
Donna Wilcock, PhD  MPI Indiana University School of Medicine
Scott Canfield, PhD MPI Indiana University School of Medicine
Feng Guo, PhD MPI Indiana University Bloomington
Jeff Dage, PhD MPI Indiana University School of Medicine
Tim Richardson, PhD MPI Indiana University School of Medicine
Kun Huang, PhD MPI Indiana University School of Medicine
Jaya Viswanathan, PhD Program Manager Indiana University School of Medicine
Karina Leal, PhD Co-Investigator Sage Bionetworks
Catia Gomes, PhD Co-Investigator Indiana University School of Medicine
Abdul Syed, PhD Co-Investigator Indiana Biosciences Research Institute
Jie Zhang, PhD Co-Investigator Indiana University School of Medicine
Travis Johnson, PhD Co-Investigator Indiana University School of Medicine
Contact us: mpsad@iu.edu

Jason Meyer, PhD
Lead PI

Bruce Lamb, PhD
MPI

Donna Wilcock, PhD
MPI

Scott Canfield, PhD
MPI

Feng Guo, PhD, MPI

Jeff Dage, PhD, MPI

Tim Richardson, PhD, MPI

Kun Huang, PhD, MPI

Jaya Viswanathan, PhD
Program Manager

Karina Leal, PhD, Co-I

Catia Gomes, PhD, Co-I

Abdul Syed, PhD, Co-I

Jie Zhang, PhD, Co-I

Travis Johnson, PhD, Co-I

Participating Institutions