Isoprenylcysteine carboxylmethyltransferase (ICMT)
In collaboration with Martin Bergö (Karolinska) we have developed an ICMT floxed mouse and a nanomolar inhibitor and are currently working on determining the effects of ICMT ablation or inhibition in a number of tumor models, including those that report immune-mediated regression. Having recently found that NRAS is uniquely sensitive to ICMT inhibition with regard to mislocalization off of the plasma membrane, we are using GEMMs to determine if ICMT inhibition will be effective in treating NRAS-driven malignancy including melanoma and hematologic malignancies. We are also collaborating with Kevan Shokat (UCSF) to develop novel ICMT inhibitors.
