Dr. Tao Wu recently joined the Department of Molecular and Human Genetics at Baylor College of Medicine as an assistant professor through a $2 million recruitment grant from the Cancer Prevention and Research Institute of Texas (CPRIT).

Wu’s research is focused on the fundamental mechanisms underlying therapeutic resistance to cancer from the epigenetics angle, which he will continue to explore.

“Baylor has excellent, state-of-art resources in molecular and human genetics and within the Dan L Duncan Comprehensive Cancer Center, which I’m excited to utilize in furthering my research into cancer epigenetics,” Wu said.

His recent research into the role of a novel epigenetic marker in the genome of glioblastoma cells may offer new strategies for targeting this lethal tumor. A study reported in Cell and led by Wu shows how a novel modification of DNA, methylation at the sixth position of the adenine base of DNA, may be one strategy by which glioblastomas, a common and lethal cancer of the brain, control the expression of genes responsible for its progression and survival. He also showed that the enzyme ALKBH1 controls this modification. This may result in the development of new drugs to target these tumors by changing their epigenetic landscape.

Wu previously had discovered this novel DNA modification in controlling stem cell fates. It differs from the commonly described methylation of cytosine residues of DNA, which has been long appreciated to be the primary method for modifying DNA to change the types of genes expressed in a particular cell. His work suggests this alternative modification also may represent a broader strategy for cells to control gene expression.

Additionally, Wu discovered a novel DNA methylation (6mA) and developed a new ChIP-Seq approach (SMRT-ChIP) in mammalian models, which he will use to systematically investigate the regulatory mechanisms underlying treatment resistance. Based on early data, this DNA methylation, called N6-mdA, appears to be the Achilles’ heel of treatment-resistant cancer cells, such as cancer stem cells.

With the CPRIT recruitment grant, Wu’s proposed research projects will examine how N6-mdA and its regulators control the development of treatment resistance in cancer stem cells and dedifferentiation models.

“Using adapted single-molecule SMRT sequencing, improved single-cell sequencing and optimized CRISPR/Cas9 screening approaches, I will explore new cancer dependencies with this novel DNA methylation and its regulators in different types of cancer,” said Wu, who also is a CPRIT Scholar. “This project promises a huge opportunity for defining novel vulnerabilities and developing new strategies to bypass or overcome the therapeutic resistance in cancer treatment.”

The understanding of this novel epigenetic player, combined with the new approaches Wu developed, will enable him to define previously unidentified vulnerabilities and develop new strategies to bypass or overcome therapeutic resistance in cancer treatment.