BLRD Research Career Scientist Award Application

Mouse models reflecting human cancers are important tools towards the translation of basic science discoveries to clinical therapies. However, rapidly evolving technologies within the last few years require further refining current approaches that enable models to be more suitable in robust translational applications to provide consistent information to meet patients’ needs. The focus of my first VA Merit award was on the contributions of altered metabolisms to melanomagenesis in vitro and in vivo. Results from these earlier studies have provided understanding and knowledge in the rational conceived strategy of our working hypothesis for our current VA Merit. In recent years, much has been learned about the molecular pathology of melanoma and significant progress has been made towards its treatment, yet late-stage melanoma still remains one of the least curable cancers with high metastatic propensity. The unique mouse models established by our group where the ectopic expression of a normal neuronal receptor, metabotropic glutamate receptor (GRM1), in normal melanocytes leads to consistent, wide-spread development of melanocytic lesions and metastasis to various organs including the lung and brain, two common metastatic sites for human melanoma. Our focus is to take advantage of the innovative model that mimic human melanoma with brain metastases to expand, improve, and transform the utility of mammalian tumor models for translational research. Completion of our proposed investigation is an essential step towards establishing fundamentally important and relevant animal models of human cancer that will improve and save cancer patient lives.