RAS Models Development

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Spheroids of mouse embryo fibroblasts (MEFs) expressing a single mutant RAS gene

Credit: Katie Powell, NCI RAS Initiative

Cancer cells grown on plastic surfaces have been a foundational technology of cancer research for decades. The search for new vulnerabilities of solid tumors has increased interest in 3-dimensional models of cancer to more closely recapitulate the environment of cancer cells in living organisms. Our group develops and supports both 2D and 3D models of cancer cells from established cell lines as well as patient-derived xenografts.

Our Progress

We have developed a panel of mouse embryonic fibroblast (MEF) cell lines that are null for endogenous RAS genes and dependent on exogenous integrated wild type or mutant RAS or RAF genes for proliferation.

We have characterized MEF lines by deep exomic sequencing, and made them available through the RAS Reference Reagents program.

With collaborators, we have screened >90 cancer cell lines with mutant or wild type RAS genes for susceptibility to knockdown of entire signaling nodes by pools of siRNAs (publication submitted).

Our Projects

  • Adapt cell lines and cells from patient-derived xenografts (PDXs) to growth in 3D
  • Characterize adapted cells in depth to understand consequences of 3D growth
  • Support drug screens using 3D models
  • Engineer organoid models to follow cell fates during propagation and perturbations

Tools We Use

  • Cell lines tagged with fluorescent proteins
  • Flow cytometry
  • RAS-dependent mouse embryonic fibroblasts
  • Next-generation sequencing

Collaborations

The RAS Model Development Group has collaborated with:

Tina Yuan
Broad Institute

Cyril Benes
Massachusetts General Hospital

Mariano Barbacid
CNIO Madrid

Esmaiel Jabbari
University of South Carolina

Contact

Dr. Rachel Bagni

Dr. Rachel Bagni, RAS Models Development Group Lead

For more information, contact the RAS Models Development Group team lead:

Dr. Rachel Bagni
301-846-5469
Rachel.Bagni@nih.gov

  • Updated: September 15, 2016