RNA—the intermediary between the genetic code of DNA and proteins—is dysregulated in nearly every type of cancer, and this dysregulation can lead to disease even without any apparent underlying genetic mutations.

Understanding the regulatory role RNA plays in cancer may lead to new types of therapies, according to Anthony Mustoe, a researcher at Baylor College of Medicine in the Therapeutic Innovation Center (THINC) and the departments of Biochemistry and Molecular Biology, and Molecular and Human Genetics. Mustoe was recruited to Baylor in 2019 with the help of a First-Time Tenure-Track Award from CPRIT, from the University of North Carolina, Chapel Hill, department of Chemistry, where he was a postdoctoral fellow.

“Because RNA is an intermediate or ‘messenger’, it has often been cast as sort of an inconsequential player in driving biology and disease,” Mustoe says. “But our lab is really interested in RNA because it plays a key role in regulating gene and ultimately protein expression. To make an analogy to an email, RNA contains the header information about where the email gets sent. You don’t want an email to your friend to go to your boss, or a thousand copies of an email to show up in one person’s inbox.”

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RNA—the intermediary between the genetic code of DNA and proteins—is dysregulated in nearly every type of cancer, and this dysregulation can lead to disease even without any apparent underlying genetic mutations.

Understanding the regulatory role RNA plays in cancer may lead to new types of therapies, according to Anthony Mustoe, a researcher at Baylor College of Medicine in the Therapeutic Innovation Center (THINC) and the departments of Biochemistry and Molecular Biology, and Molecular and Human Genetics. Mustoe was recruited to Baylor in 2019 with the help of a First-Time Tenure-Track Award from CPRIT, from the University of North Carolina, Chapel Hill, department of Chemistry, where he was a postdoctoral fellow.

“Because RNA is an intermediate or ‘messenger’, it has often been cast as sort of an inconsequential player in driving biology and disease,” Mustoe says. “But our lab is really interested in RNA because it plays a key role in regulating gene and ultimately protein expression. To make an analogy to an email, RNA contains the header information about where the email gets sent. You don’t want an email to your friend to go to your boss, or a thousand copies of an email to show up in one person’s inbox.”

Mustoe’s lab is interested in where that type of information is encoded in RNA and how it is dysregulated in cancer, in which RNA may end up in the wrong place or in inappropriate amounts. Dysregulation of RNA can cause proteins that promote cancer to be over-expressed and proteins that suppress tumors to be under-expressed, even without any underlying genetic mutations in those genes.

“What can happen is that there is a mutation somewhere in a totally different gene whose purpose is to regulate a cancer gene at the RNA level,” Mustoe says. “In the email analogy, you’ve damaged the postman, who no longer can read the delivery instructions properly. Even though the message is the same, the gene is fine, some other player in this regulatory system has been mutated and that is now causing the dysregulation of the cancer-causing gene.”

Using a combination of experimental and computational approaches, Mustoe is currently studying RNA metabolism in triple-negative breast cancer. In this cancer, there is often no single clear driving mutation that causes it, and Mustoe thinks it makes a good system for understanding the role of RNA in the initiation and promotion of cancer. But he says his lab is driven by the basic understanding of cancer mechanisms, rather than by an individual cancer type, and hopes his findings will be applicable to many different types of cancers.

Ultimately, he envisions RNA therapeutics for treating cancers. “One of the hopes of RNA therapeutics is the potential for custom drugs that precisely target patient-specific mutations,” he says. “This level of customization is just frankly impossible in the traditional route of targeting proteins. It’s many years down the road but we hope that we can get to that point.”

He says CPRIT funding has enabled him to tackle “big risky questions that I normally wouldn’t feel comfortable or able to tackle because those resources allow me to make big bets, with the understanding that some of them may not work out but with the hope that a few of them will.” He appreciates the biological expertise of the Baylor community, which, he says, complements his computational biophysics and chemistry background.

Mustoe received his undergraduate education in chemical engineering and mathematics at Washington University in St. Louis, and his Ph.D. in biophysics from the University of Michigan. He began his postdoctoral fellowship at UNC in 2014.

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