Isaac López-Moyado, Ph.D.

Can we take advantage of a vulnerability in cancer cells to preferentially kill them?

There are certain points in DNA replication and gene expression when a strand of RNA can slip between the two strands of DNA. This crossed-over RNA can recombine with one side of the DNA strand, forming an RNA-DNA hybrid. Although RNA-DNA hybrids are a normal part of (cellular) life, many types of cancers show increased levels of RNA-DNA hybrids.

RNA-DNA hybrids can be a source of DNA damage. Cells have ways of counteracting this danger, and there is a large network of proteins preventing aberrant accumulation of RNA-DNA hybrids in healthy cells. My preliminary experiments in a mouse model have revealed that—in cancer cells that display increased levels of RNA-DNA hybrids— we can inactivate the proteins that normally prevent the accumulation of these hybrids and cause cancer cells to disappear.

My hypothesis is that inactivating the proteins that prevent the accumulation of RNA-DNA hybrids in cancer cells will impair their proliferation by exacerbating RNA-DNA hybrids and DNA damage, leading to cancer cell death.

SPARKing Impact: Cancer cells show increased levels of RNA-DNA hybrids. I aim to exploit this attribute of cancer cells as their Achilles’ heel. My project will explore whether inducing even further accumulation of RNA-DNA hybrids will kill cancer cells, representing a new therapeutic opportunity.