MacPherson, David

Faculty Profile

First Name: 
David
Last Name: 
MacPherson
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Title: 
Assistant Member
Primary Institution: 
FHCRC
Department/Division: 
Human Biology
Department/Division: 
other
E-Mail: 
Mail/Box #: 

358080/D4-100

Office Location: 

1100 Fairview Ave. N., Room D4-112

Office Phone: 
(206) 667-6464
Alternate Phone: 
(206) 667-7618
Research

Research Summary: 

Our laboratory is focused on understanding the mechanisms through which cancer-mutated genes drive tumorigenesis. We study two tumor types, small cell lung carcinoma (SCLC) and retinoblastoma. Genomic analyses of human tumors allow us to identify gene mutations that may contribute to tumor initiation, progression and metastasis.  It is a challenge to determine which cancer-mutated genes function as oncogenes or tumor suppressor genes.  We turn to genetically engineered mouse models to probe the activity of genes implicated in SCLC or retinoblastoma.

Children who inherit a mutant copy of the RB gene develop retinoblastoma with extremely high frequency.  We have generated some of the first RB-knockout mouse models of retinoblastoma. We recently used these models to identify a microRNA cluster, miR-17~92 that synergizes with RB loss to drive uncontrolled proliferation and tumor formation.

RB is frequently mutated in SCLC, the most aggressive form of lung cancer. SCLC is tumor with neuroendocrine characteristics.  Typically, SCLC has metastasized by the time it is diagnosed and survival rates for metastatic SCLC are dismal. Unlike other forms of lung cancer there are no targeted therapies for SCLC. We have recently undertaken efforts to identify the major driver genes mutated in human SCLC using next-generation sequencing. A number of projects in the lab are now aimed at exploring the functions of new SCLC-mutated genes using mouse genetics. Our ultimate aim is to translate increased understanding of the basic biology of SCLC driver genes to the development of novel therapies for human SCLC.

Short Research Description: 
cancer genetics, mouse models of lung cancer
Areas of Interest: 
Cancer Biology
Gene Expression, Cell Cycle & Chromosome Biology
Genetics, Genomics & Evolution
Keywords: 
<p> cancer genetics, mouse models, RB, small cell lung carcinoma, retinoblastoma, genomics</p>
Publications

Taking Students
Year: 
2014 - 2015