Engelward Lab: DNA Damage Induced Loss of Genomic Integrity

What causes cancer? Cancer is a disease of the genome that is caused by accumulated mutations in oncogenes and tumor suppressors. Our mission is to understand what causes those mutations, how our cells protect the genome, and how our environment puts us at risk for tumorigenic mutations.

Homologous recombination is a critical DNA repair process, but excessive homologous recombination can lead to deleterious large scale sequence rearrangments that promote cancer and aging. Our laboratory has developed novel technologies for detecting homologous recombination events, both in cells and in whole animals. Indeed, it is now possible for the first time to actually see fluorescent recombinant cells within normal tissues. Our technologies have enabled basic research showing that chemicals are highly recombinogenic, that cell division can be a major driver of mutation accumulation, and that recombination events can be induced by epigenetic changes.

Great scientific advances result from disruptive technologies that allow us to see things, and do things, never before possible. In addition to fluorescence detection of recombination, we are developing technology for high throughput DNA damage analysis in human cells. In collaboration with Sangeeta Bhatia’s laboratory, we have created a novel array-based DNA repair assay that exploits microfabrication technology. Our platform can be used as a genotoxicity assay, as a tool for drug discovery and as a way to detect genotoxic agents in our environment. Further, it only requires basic laboratory equipment, enabling detection of genotoxic agents in developing nations.

It is our hope that by helping to delineate the major factors that drive tumorigenic mutations, and by creating technologies to detect DNA damage, research in this laboratory will contribute to understanding that helps shape prevention strategies that impact human health.