MacPHERSON LAB

Welcome to the MacPherson Lab

Our laboratory investigates the mechanisms through which cancer-mutated genes drive tumorigenesis. Much of our current work is focused on small cell lung carcinoma (SCLC), a highly aggressive neuroendocrine cancer. Typically, SCLC has metastasized by the time of diagnosis, and survival rates are dismal. We identified major driver genes mutated in human SCLC using next-generation sequencing approaches. To explore key activities of SCLC-mutated genes we use mouse genetics and functional studies. We have generated a panel of new mouse models of SCLC. These models, along with derived cell lines, are employed to understand how mutations in certain genes promote SCLC and to identify vulnerabilities conferred by these mutations.  Genomic analyses (DNAseq, RNAseq, ChIPseq, ATACseq etc.) and functional genomics (whole genome CRISPR screens) are used in these efforts.

We have become particularly interested in understanding cancer-mutated genes that alter chromatin, as in general, there is a poor understanding of how such mutations drive cancer.  We use mouse models to explore tumor suppressor roles for histone methyltransferases, acetyltransferases and other cancer-mutated chromatin regulating genes.  These research directions are extending beyond SCLC to also include other solid tumor types.

Our ultimate aim is to translate an increased understanding of the basic biology of SCLC driver genes to the development of novel therapies for a cancer type greatly in need of new therapies.  Working with our clinical colleagues at the Seattle Cancer Care Alliance, we study genomic changes in circulating tumor cells (CTCs) isolated from SCLC patients and we generate patient derived xenograft (PDX) models of SCLC.  Both PDX and genetically engineered mouse models are used for studies that try to link mutations in key SCLC driver genes to exceptional responses to novel therapies.  

MRI imaging Showing tumor Progression over 5me in A mouse model Of SCLC