Scientists Awarded $2.25 Million to Study Key Mechanisms Behind Some Cancers

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded a pair of grants totaling more than $2.25 million to study the assembly mechanisms that lie at the root of various cancers.

The grants come from the National Institute of General Medical Sciences of the National Institutes of Health (NIH) and the Department of Defense (DoD).

Katrin Karbstein, a TSRI associate professor, is the principal investigator of the four-year NIH study, which will be carried out in collaboration with the lab of structural biologist Elizabeth Stroupe at Florida State University. The two-year Department of Defense study will be led by Karbstein and John Cleveland of the H. Lee Moffitt Cancer Center and Research Institute.

Karbstein’s research focuses on the assembly of ribosomes—large macromolecular machines required for cell growth that translate RNA into proteins. Defects in the assembly process can lead to serious problems, including cancer.

The NIH-funded study takes a broad look at the ribosome assembly process to unravel the mechanisms by which defects in ribosome maturation can lead to tumors.

“Defects in assembly of the mRNA binding channel, for example, can lead to birth defects, including Diamond Blackfan Anemia—which has been associated with a 30- to 40-fold increased incidence of colon cancer, osteosarcoma and leukemia,” Karbstein said.

For the new DoD-funded study, the team is working to uncover new ways to disrupt the regulatory circuit that promotes aggressively prolific forms of breast cancer. The research will explore the potential of a drug candidate developed in the laboratory of William Roush, a TSRI professor, associate dean of graduate studies and executive director of medicinal chemistry.

This project will focus on the molecule casein kinase 1d (CK1d), which is essential for human ribosome assembly and has been shown to be an important therapeutic target.

“We think this research could accelerate the development of new drugs directed against triple negative breast cancer by expanding our understanding of the action of these new CK1d inhibitors,” Karbstein said.

The number of the NIH grant is 1R01GM117093; the DoD grant, W81XWH-16-1-0009.

Send comments to: press[at]scripps.edu