Dmitri Petrov, Ph.D.

Institution: The Board of Trustees of the Leland Stanford Junior University (Stanford)

Project: Barcoding Genetic Changes May Give Insight Into Lung Cancer

Grant(s): Lung Cancer Discovery Award

Lung cancer is an extremely complex disease because it is driven by a constellation of distinct genetic changes. Cancer sequencing efforts have defined prevalent genetic changes common in tumors. But how these genetic changes work together to drive tumor growth remains to be determined. We plan to dramatically improve a very powerful preclinical model of cancer that we developed previously. Our approach, called Tuba-seq, allows us to grow and follow individually tens of thousands of individual tumors in the mouse lung. Tuba-seq barcodes each tumor to uniquely identify the genetic changes and quantify tumor size. These tumors have predefined genetic changes generated using CRISPR and other techniques. CRISPR is a new kind of genetic engineering that allows scientists to edit DNA much more easily than before. We will extend Tuba-seq to allow creation of more complex and more realistic tumor genotypes (the set of genes in DNA responsible for a particular trait) necessary for modeling of human tumors.


Our next phase of research will use knock-out mice. These are genetically modified mice in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA. We aim to expand the capacity of the Tuba-seq system to allow for simultaneous knock-outs of multiple tumor suppressors in our state-of-the-art mouse model of lung cancer and thus learning about the fitness landscape of lung cancer.

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