NIH ‘High Risk-High Reward’ grants go to two UF Health researchers exploring strategies to fight cancer and other diseases

Two University of Florida Health researchers have received prestigious High Risk-High Reward grants from the National Institutes of Health’s Common Fund for their trailblazing proposals to tackle cancer and other diseases, the NIH announced today.

Chemist Thomas Kodadek, Ph.D., has been awarded a Transformative Research Award grant worth up to $4.1 million over five years to study whether new potential therapeutics designed to lure disease-driving proteins directly into cells’ internal disposal machinery could be a promising strategy against cancer and other diseases. Kodadek is a chemistry professor at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology in Jupiter, Florida, and a member of the UF Health Cancer Center. It is Kodadek’s third Transformative Research Award. He also received an NIH Director’s Pioneer Award in 2005.

“These grants support unconventional approaches to major biomedical research challenges,” Kodadek said. “We hope to be able to make major inroads developing a new class of drug candidates using these resources.”

Mohammed Gbadamosi, Ph.D., a postdoctoral fellow in the University of Florida College of Pharmacy, has secured a High Risk-High Reward grant called an Early Independence Award. Gbadamosi’s grant, worth up to $1.25 million over five years, will enable him to launch his own independent academic research laboratory. Gbadamosi said he will build a multidisciplinary research team within the college focused on developing treatment strategies that combine chemotherapy and immunotherapy to combat aggressive breast cancer and other cancers impacted by health disparities.

Applying artificial intelligence, his lab plans to construct computer models for personalizing combined treatment strategies based on a patient's tumor genetics, he said. The High Risk-High Reward program’s early independence awards enable exceptional junior scientists to skip traditional postdoctoral training and move immediately toward independence.

“With this award, I look forward to conducting excellent science and investing in the next generation of trainees, as others have invested in me,” Gbadamosi said. “The gratitude I have for receiving this award cannot be put into words, and I’m incredibly grateful to God, my mentors, colleagues, family and everyone who helped me realize this achievement.”

The High-Risk, High-Reward program of the NIH’s Common Fund encourages investigators to pursue new ideas in any area of research relevant to the NIH’s mission to advance knowledge and enhance health. The NIH said today it was issuing six Transformative Research Awards and 13 Early Independence Awards for 2023.

“These awards align with the Common Fund’s mandate to support science expected to have exceptionally high and broadly applicable impact,” said Robert W. Eisinger, Ph.D., acting director of the Division of Program Coordination, Planning, and Strategic Initiatives at the NIH.

Kodadek hopes that the strategy he has proposed could be applied to many difficult-to-treat diseases affected by the buildup of excess or mutated proteins within cells. Recent research has revealed the nature of genes and proteins that drive disease progress. Unfortunately, making medications to act on many disease-driving proteins has proven unworkable. Existing drugs often work by binding to a disease-causing protein, thereby blocking its activities. But once the drug clears the body, the protein becomes a problem again. So only drugs that bind and remain engaged with their targets for long periods of time are effective. For many diseases, scientists have been unable to find such compounds.

Recently researchers have developed an alternative strategy, in which, rather than merely inhibiting a target protein, the drug molecule sparks its destruction. This is achieved by building compounds that engage the protein target and drag it to a complex inside of all cells called the proteasome, which results in its destruction. The proteasome resembles a paper shredder that chews up protein molecules. Its normal job in cells is to destroy proteins the cell no longer needs. This new class of drugs called “degraders” directs the proteasome to eliminate disease-causing proteins.

A few of these drugs are now entering clinical trials, mostly for cancer applications. But a major concern is that they work through a complicated, indirect process, providing many opportunities for cells, particularly cancers, to mutate rapidly and acquire resistance to the drug.

Kodadek plans to develop a new class of degraders that recruits a disease-causing protein directly to the proteasome, without the intermediate steps. He believes this will reduce the opportunity for cells to develop drug resistance.

“Our preliminary studies look encouraging, but there are many questions to answer before we know if this strategy will be the one that works for these hard-to-treat diseases,” Kodadek said. “I’m grateful to the NIH and the National Cancer Institute for enabling our lab to fully explore these questions.”

The Wertheim UF Scripps Institute and the UF College of Pharmacy are part of UF Health, the University of Florida’s academic health center. UF Health consists of six health colleges, 10 research centers and institutes, 11 hospitals — including two teaching hospitals and five specialty hospitals — and a host of physician medical practices and outpatient services. The Wertheim UF Scripps Institute joined UF Health in 2022.