The UofL team, led by John O. Trent, professor of medicine and deputy director of basic and translational research at the Brown Cancer Center and Jonathan B. Chaires, professor of medicine, used the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory near Chicago, to define and model the longer genetic sequence structures that are believed to be the source of changes that mutate healthy cells into cancer cells.

Previous methods limited most studies to strings of fewer than 33 nucleotides. The new model developed by the UofL team enables researchers to study sequences of up to 70 nucleotides, which may provide more accurate targets for drug intervention.

By combining multiple processes, the team developed models of the G4 quadruplex structures that can be used in computer analysis to virtually test how drug and disease molecules might interact with these sites before real-world testing in the lab. This testing may aid in the discovery of drugs that could inhibit the mutation process for oncogenes c-Myc, c-Kit and k-Ras, which are associated with lung, pancreatic, colon and other cancers.

“Using integrative structural biology, we can determine that these oncogene promoters can form unique, complicated higher-order structures. We can use these structures for discovering specific inhibitors to stop gene transcription at the DNA level without nonspecific DNA-binding side effects,” Trent said. “This opens up targeting DNA by therapeutics like we target proteins.”

The research to develop the model was published in earlier this year. A profile of the team’s work has been  and will be featured in their annual report later this year.

The team now has begun using this structural understanding and the new models in ongoing anti-cancer drug discovery work, which includes data processing using the combined power of computers located in K-12 schools across Kentucky. The dual-purpose computer grid is a partnership with Dataseam, established in 2003 and funded by the Kentucky General Assembly to provide computing infrastructure, workforce development and educational opportunities for students and staff in Kentucky school districts.

Fellows are selected for their “spirit of innovation” in university research, helping to generate groundbreaking inventions that have a tangible impact on quality of life, economic development and the welfare of society.

Trent is the only 2020 fellow from the state of Kentucky and the seventh from UofL. The 2020 Fellow class of 175 inventors represents 115 research universities and governmental and non-profit research institutes worldwide.

“It’s certainly an honor and I think it’s a testament to the drug discovery program we’ve built at the Brown Cancer Center and UofL through many collaborations and partnerships,” said Trent, a professor of medicine and the Wendell Cherry Endowed Chair in Cancer Translational Research. “The benefits of UofL are the support we’ve had for taking creative activities through intellectual property protection to the commercialization grant programs.”

As deputy director of basic and translational research at the , Trent’s Molecular Modeling Facility uses computer predictions to understand and virtually test how drug and disease molecules might interact before real-world testing in the lab.

Trent also runs the UofL partnership with , a company that created a grid that uses the processing power of thousands of computers in schools across Kentucky that Trent uses to screen potential drugs and compounds against and, most recently, . The DataseamGrid has the capability to screen millions of potential compounds against molecular targets in only a few days.

Trent holds more than 50 patents, 24 of which are U.S., and numerous licenses and option agreements with potential commercial partners. Among other accolades, he received the Apple Science Innovator Award and the 2019 , the latter awarded through the UofL Commercialization EPI-Center.

“We’re very proud of John, and all his work to create innovations that have the power to advance our health,” said Kevin Gardner, UofL’s executive vice president for research and innovation. “The fact that John and other UofL researchers before him have received this honor, the highest for academic inventors, shows our university’s commitment and leadership in research, invention and developing technologies that change and improve the way we work and live.”

Previous Fellows from UofL include Suzanne Ildstad and Kevin Walsh (2014), William Pierce (2015), Paula Bates (2016), Robert S. Keynton (2017) and Ayman El Baz (2019).

Trent’s induction, paired with Bates’ four years earlier, also makes the two of them one of only a handful of married couples to be named fellows. The duo also frequently works together, including developing the aptamer that would become the basis for innovative technologies since applied to fight and novel .

The 2020 NAI Fellow class collectively holds more than 4,700 issued U.S. patents.

Among the class are 24 recipients of National Academies of Sciences, Engineering, and Medicine honors, six recipients of American Academy of Arts & Sciences honors and two Nobel Laureates, as well as other honors and distinctions. The complete list of 2020 NAI Fellows is available .