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Matthew Meyerson M.D., Ph.D.
This grant is being fully funded by Elliot's Legacy, through the Uniting Against Lung Cancer Grant Program
Lay Description
Small cell lung cancer is a deadly disease with no curative treatment. The goal of this project is to discover genetic changes that drive the formation of small cell lung cancer. We then intend to evaluate these genes as targets for the treatment of this disease. Our proposal contains three parts. First, we will identify genes that are required for the survival of small cell lung cancer cells, by selectively blocking the activity of every gene in both small cell lung cancer cells and normal cells and comparing our results. Second, we will systematically determine the DNA sequence of all the genes in a set of small cell lung cancer samples, and identify how these sequences depart from normal human gene sequences. Third, by combining the data sets from our first two aims, and validating our results with a series of functional tests, we intend to identify the best genes as targets for future drug development.
Scientific Abstract
The advent of genome-wide RNA interference approaches and single molecule sequencing technologies now makes it possible to identify candidate oncogenes, by determining gene essentiality and genomic alterations, respectively. Small cell lung cancer (SCLC) is particularly suitable for such studies because there are no targeted therapies and few dominant oncogenes known. In this study, we propose to search for both essential genes and genomically altered genes in a set of small cell lung cancer (SCLC) cell lines that are paired with normal control cells. First, we will infect eight SCLC cell lines with a whole-genome pooled short hairpin RNA (shRNA) library, and identify those shRNAs that specifically lead to decreased SCLC survival. Second, we will perform whole transcriptome sequencing analysis to identify mutated and re-arranged cDNAs. Third, we will intersect these data sets and begin to perform functional validation of candidate oncogenes by ectopic expression.
Uniting Against Lung Cancer is funding research in 22 states
Uniting Against Lung Cancer is now also funding research in British Columbia, Canada
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