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Pharmacy Professors Brueggemeier, Li, Li and Molecular Genetics Professor Fisk Receive Pelotonia Award to Develop Compound for Triple Negative Breast Cancer
The Ohio State University Comprehensive Cancer Center and Arthur G. James Cancer Hospital and Stefanie Spielman Fund have granted a $100,000 Pelotonia Award to College of Pharmacy faculty members Robert Brueggemeier, Chenglong Li, Pui-Kai Li and Department of Molecular Genetics professor Harold Fisk to conduct early phase drug discovery research on Mps1, a unique protein found to be extremely active in triple negative breast cancer (TNBC). The team will work toward designing, developing and evaluating a compound that inhibits Mps1 and can be used in TNBC treatment.
TNBC is a form of breast cancer defined by the absence of estrogen receptors, progestrerone receptors and HER2, which are typically targeted in breast cancer treatment processes. These tumors are aggressive and resistant to most available therapy. Based on previous research by the group, their aim is to prove the effectiveness of targeting Mps1 in TNBC and other aggressive forms of breast cancer.
“The lack of an identified receptor in these aggressive forms of breast cancer has made the treatment of them particularly difficult,” said Pui-Kai Li. “Our research up to this point has been promising in identifying Mps1 as a possible target, but now we must begin more rigorous testing to see how effective this therapy can be.”
Chenglong Li’s lab will be tasked with designing the compound. Pui-Kai Li’s lab will make the compound to be used in the in-vivo model. Fisk’s lab will lead biochemical and cellular testing in the trials, and Robert Brueggemeier will evaluate the inhibitors in breast cancer cells and in-vivo trials.
“Our previous work has led to the identification of two binding sites on the Mps1 protein for the compound,” said Chenglong Li. “These sites will allow us to add and replace fragments to improve drug properties and potency in the treatment process.”
Fisk, who has spent the majority of his career conducting research on Mps1, will bring his expertise on the cellular functions of Mps1 to the group, and analyze how the protein’s production of extra centrosomes (i.e., an organelle that serves as the main microtubule organizing center of the animal cell as well as a regulator of cell-cycle progression) contributes to the proliferation of TNBC cells.
“Every indication from our research leading up to this suggests this compound should be effective in suppressing TNBC cells,” said Fisk. “For me as a basic scientist, it will be interesting to see why this compound is effective, and it will be exciting as our labs collaborate and use this information to come up with the most potent treatment process.”
While the project is in its early stages, the team hopes its research will culminate in development of a drug that can be put through human trials. The project will also examine therapies featuring a combination of Mps1 inhibitors and current treatment regimens to produce the most efficacious results.
“This has been a total team effort,” said Brueggemeier. “This is truly a reflection of how collaborative things are at Ohio State. This project is far from over, and we look forward to working together and adding more members to our team as this project grows.”