Disease Modeling Core

Overview

The Disease Modeling Core (DM core) provides diabetes researchers with access to novel human stem cell-derived in vitro cell models for investigating cellular and molecular features of both Type 1 and Type 2 diabetes. Recent progress in stem cell, organoid culture, gene editing and directed differentiation technologies has afforded opportunities to develop state-of-the-art pre-clinical human models.The goal of DM core is to provide the expertise, infrastructure and access to novel human model systems and technologies to DRC investigators. This includes expertise, resources and training in start-of-the-art stem cell technologies together with rigorous quality control testing, validation standardization and authentication all model platforms and reagents.

Access to control and engineered stem cell (iPS and organoid) lines:
With the developing ability to modify the genome of human stem cells, we anticipate that increased numbers of such cell lines will be available in the near future. However, obtaining, authenticating and verifying genetically modified cell lines with potentially broad application is cost prohibitive to individual researchers. We are establishing a repository for such cell lines, including quality control data by our core, including iPS cell and adult stem cell organoid lines. This resource will be further expanded as new lines become available and represent an invaluable resource to the DRC community at UC-AMC.

  • human iPSC lines from control individuals – some established, in progress
  • human iPSC lines from individuals with T1D- some established, in progress
  • human iPSC lines from control individuals with constitutive fluorescence marker expression- in progress
  • human iPSC lines from control individuals with constitutive firefly luciferase expression- in progress
  • human iPSC lines from control individuals with recombination cassette exchange competence - in progress
  • human iPSC lines from control individuals with inducible Cas9 nuclease expression- in progress
  • patient specific organoids from control individuals- in progress
  • patient specific organoids from control individuals with fluorescence marker expression- in progress

Consultation, access, training, implementation of genome editing technology in endodermal derived cells and tissues:
The DM core provides researchers with access to controlled and validated resources that will increase investigator productivity, offer more precise control over experiments and support higher standards in documentation of research findings. In addition, we offer custom genome editing approaches, as well as site specific targeting of insulate loci (eg. AAVS1), to DRC members.

  • iPSC based approaches
  • adult stem cell derived organoid based approaches
  • Plasmid and cloning services for genome engineering
  • Genetic targeting of insulated AAVS1 safe harbor loci in stem cells
  • Gene correction, endogenous gene tagging and genetic disease modeling

Rapid generation of patient iPSC and adult stem cell-derived organoid lines to establish novel disease models:
We provide DRC members with the unique opportunity to combine easy access to patient samples through the Clinical Research (CR) core with the ability to reprogram them into iPSC lines. This allows  the rapid and efficient generation of novel disease models.

Provision of transdifferentiation/ reprogramming/differentiation of endoderm derived cells and tissues:
Efficient generation of functional beta-like cells has been successfully described by only a handful of labs. However, it has recently proven to be an extremely useful cell source for human beta cells and there is a large demand for these beta-like cells within the wider diabetes research community. We will provide iPS derived beta-like cells to DRC researcher at a fee-for-service resource in the future.

    Perifusion assays to determine pancreatic islet function:
    The core provides a perifusion service to determine the function of pancreatic islets function in a dynamic manner using an automated Biorep machine with up to 8 simultaneous sample runs. Hormone secretion is assayed using commercial available ELISA kits, eg for Insulin or Glucagon. 

    Molecular biology core:
    We deliver a  wide variety of quality control and authentication services at reduced cost to DRC users. The core is located on the 4th floor of the Barbara Davis Center in close proximity to other DRC cores and research laboratories. 


    • Sanger sequencing
    • Cell line authentication
    • Mycoplasma testing (gDNA and supernatant)
    • Bioanalyzer (RNA integrity)

    Peter Dempsey, PhD
    Co-Director
    peter.dempsey@cuanschutz.edu

    Peter Dempsey cropped 

     

    Mark Farrell
    Molecular Services
    mark.farrell@cuanschutz.edu

    Mark Farrell cropped

     

    Sean McGrath, PhD
    Organoid Services
    partrick.mcgrath@cuanschutz.edu

    Sean cropped

    Stem Cell & Organoid Services:
    Peter Dempsey, peter.dempsey@cuanschutz.edu
     
    Molecular Services:
    Mark Farell, mark.farrell@cuanschutz.edu

     

    CMS Login