Our research utilizes mouse models to study genetic drivers of tumorigenesis and the impact of new drugs involved in cancer diagnosis or therapy.
Research in the Collier laboratory utilizes genetic approaches to elucidate the mechanisms of cancer initiation and progression. Through studying a spontaneous mouse model of leukemia, we have discovered an allele of Mcm4 that acts in a dominant manner to promote genomic instability and tumorigenesis. Mcm4 functions during DNA replication and we are now using this model to study how replicative stress promotes genomic instability, and are using transposon mutagenesis to discover genes that cooperate with replication stress to promote tumorigenesis.
In a separate study, we used transposon mutagenesis in mice to identify Csf1 (Macrophage colony stimulating factor 1) as a candidate glioma oncogene. Through transgenic models we have shown that Csf1 overexpression in the brain dramatically increases microglial numbers and accelerates gliomagenesis in a transgenic glioma model. We are now studying the mechanisms by which Csf1 increases microglial numbers and impacts microglial phenotypes.
In addition to mechanistic studies we are utilizing our mouse cancer models for pre-clinical testing of novel imaging agents and targeted therapies. We are using our leukemia models to test if a novel imaging/therapeutic agent has efficacy in diagnosing and treating hematologic cancers. We are using our Csf1 and glioma models to test the impact of a small molecule inhibitor of the CSF1 receptor on microglial phenotypes and glioma development. As high levels of Csf1 are found in multiple CNS diseases, the results of this study may have therapeutic implications in many CNS pathologies.