Human diseases are increasingly linked to modifications of the genome that allow genes to be turned on and off, not just to mutations in DNA sequences. Understanding these so-called epigenetic modifications is crucial for understanding what drives cancer and in developing new therapies to combat it.

Now a bioengineer at Rice University is using genome editing and epigenetic modification tools in cells to explore the effects of epigenetics on disease, particularly cancer.

Isaac Hilton was recruited in 2018 from Duke University, where he was a postdoctoral associate in genome and epigenome editing, with the help of a First-Time Tenure-Track Award from CPRIT. He joined the Department of Bioengineering at Rice.

Read More

Human diseases are increasingly linked to modifications of the genome that allow genes to be turned on and off, not just to mutations in DNA sequences. Understanding these so-called epigenetic modifications is crucial for understanding what drives cancer and in developing new therapies to combat it.

Now a bioengineer at Rice University is using genome editing and epigenetic modification tools in cells to explore the effects of epigenetics on disease, particularly cancer.

Isaac Hilton was recruited in 2018 from Duke University, where he was a postdoctoral associate in genome and epigenome editing, with the help of a First-Time Tenure-Track Award from CPRIT. He joined the Department of Bioengineering at Rice.

Hilton is using genome-editing tools developed for making changes to the base-pair sequence of DNA, and adapting them to epigenetically silence or turn on certain genes. CRISPR/Cas9 technology was developed to cut out a damaged gene sequence and replace it with a new one. Hilton says it is easily adapted to target a gene without making a cut. He uses the same targeting technology as CRISPR, but instead of cutting the DNA strand, he delivers a payload that will essentially stick to the DNA without cutting it, and either turn on or turn off a specific gene.

When cells ignore cellular signals to stop proliferating, or respond to signals that cause them to grow out of control, that’s when cancer develops or progresses. “Often we want to turn on a gene that will have therapeutic benefit that has been unnaturally silenced,” he says. “Conversely, we can silence genes that in cancer cells have been turned on too much.”

So far he is only working with cancer cell lines in culture, initially with blood cancers, like leukemias and B-cell lymphomas. But the tools he is developing will be relevant for essentially any human cancer, he says. He’s hoping to find the crucial epigenomic alterations that initiate, cause metastasis or progression, and determine the severity of breast, lung, cervical, and colorectal cancers.

Knowing the functional importance of epigenetic modifications may allow them to eventually be used as biomarkers for sensing cancer progression and severity. The cellular models Hilton is developing could also provide platforms for developing new cancer drugs or for screening for the effectiveness of chemotherapy.

Hilton is currently focused on cellular models of human disease, but plans to expand his research program to include similar experiments in mice.

This might ultimately provide a path to cancer treatment in human patients. Hilton’s long-term goal is to find a way to translate this technology into new types of therapies, which could be used alone or in combination with other treatments. “We potentially have therapeutic modalities that could have a very large impact,” he says.

In addition to the lure of CPRIT funding to enable him to jumpstart his laboratory, Hilton says he was drawn to Texas by fantastic collaborators and colleagues at Rice and the Texas Medical Center, the friendliness of Texans, and vibrancy and economic growth of Houston.

Hilton received his undergraduate degree in biological sciences from the University of Missouri–Columbia, and his Ph.D. in genetics and molecular biology from the University of North Carolina, Chapel Hill. He began as a postdoctoral associate at Duke in 2013. Hilton is an inventor on patents related to technologies for genome and epigenome engineering.

Read Less