Assistant Professor Raed Rizkallah received a $384,028 award from the National Institutes of Health and National Institute of General Medical Sciences to better understand an enzyme that may be a viable target for cancer therapy.
The enzyme, called TOPK, has been found to be highly expressed in most cancer cells and its high expression has correlated with poor patient prognosis.
Rizkallah’s project entitled, “Mechanisms of the Mitosis-Specific Activation of the Oncogenic Kinase TOPK,” seeks to further the knowledge of the functions and regulations of the TOPK enzyme and identify the mechanisms by which it contributes to cancer development.
“We all start life as one cell, which then grows and divides an astronomical number of times to generate the trillions of cells that form the adult person,” explained Rizkallah. “These cycles of growth and division are tightly controlled by finely-orchestrated biochemical signaling pathways. Disruption of the normal execution of these pathways leads to developmental abnormalities or lethal diseases, like cancer.”
In the mitosis stage of the cell cycle, the TOPK enzyme is activated. Mitosis is the final step in the cell cycle during which a cell divides into two daughter cells. Also during mitosis, a process known as gene expression is briefly “paused.”
Gene expression is when the information stored in the DNA is converted into instructions for making proteins or other molecules. Currently, scientists lack proper insight to understand how the proteins that control gene expression are regulated during mitosis.
Rizkallah and his team previously discovered a biochemical mechanism that can disable a large number of these gene regulators during mitosis. They also learned that the TOPK enzyme regulation may be responsible for this important mitotic function.
“Interestingly, this enzyme we identified, TOPK, was found by other research groups as an important protein contributing to tumorigenesis, [the production or formation of tumors], and it was found to be highly expressed in most cancer cells, but not in normal cells,” he added. “These findings suggest that TOPK is a very promising target for cancer therapy.”
With support from the grant, Rizkallah’s research will be conducted over the next three years and will focus on understanding how to efficiently target TOPK in future therapeutic approaches.
