AU Research Fellow exploring effectiveness of proteasome inhibitors for treating tumors
by Mitch Emmons
Cancer research is not typically associated with undergraduate activities, but one of Auburn University’s undergraduate research fellows is doing just that.
Laura Downey, of Arlington, Texas—a junior majoring in biomedical sciences with a premedical concentration and minors in public health and dance—is among the 2021 recipients of AU’s Undergraduate Research Fellowship. Downey is exploring the effectiveness of proteasome inhibitors for the treatment of solid tumors. She is mentored in her work by Dr. Alexei Kisselev in the Department of Drug Discovery and Development in the Harrison School of Pharmacy.
“The ultimate goal of this project is to expand the use of proteasome inhibitors by determining their clinical effectiveness for the treatment of solid tumors,” Downey said.
Kisselev explains: Proteasome inhibitors (PIs) are a class of FDA-approved drugs used in the treatment of such cancers as multiple myeloma – a bone marrow cancer - and mantle cell lymphoma – a non-Hodgkin lymphoma cancer of the immune system. PIs work by blocking the action of proteasomes, cellular complexes that recycle damaged proteins. If proteasome function is blocked, the cell becomes clogged with “garbage” proteins, prompting them to destroy themselves. Cancer cells produce more “garbage” protein than normal cells and are, therefore, more sensitive to proteasome inhibitors. But their effectiveness in the treatment of solid tumors is a yet largely unexplored research area.
“What my research project focuses on is the use and clinical effectiveness of these PIs for treatment of solid tumors by targeted delivery,” Downey said.
Downey writes in her project abstract:
“Proteasome inhibitors, bortezomib, carfilzomib and ixazomib, are currently used for the treatment of multiple myeloma, a bone marrow cancer. However, these FDA-approved proteasome inhibitors have potential to expand treatment of other cancers using liposomal nanoparticle packaging. This allows for selective delivery into solid tumors, reducing toxicity to normal tissues and protecting inhibitors from metabolic inactivation.”
Downey became interested in this area of cancer research and medicine during high school.
“I got the opportunity to shadow an oncologist as part of my high school studies,” Downey said. “I became interested in different types of cancer treatments. I knew coming to Auburn that I wanted to get involved in research, so when Dr. Kisselev needed an undergraduate student for his anti-cancer drug discovery research, I knew that was something I wanted to be a part of.”
Downey’s study uses the mouse model in which she studies breast cancer.
“The mice, which have breast cancer cells in their mammary glands, are injected with the PI drugs and we monitor growth of the cancerous cells for positive or negative results,” Downey said.
“What we have observed thus far suggests that there was a selective targeting in the tumor with no observed effects in normal tissues. These results indicate promise that these PIs can be effective in the targeted delivery treatment of tumors.”
Downey hopes to attend medical school after completing her degree program at Auburn and to specialize in oncology.
The AU Undergraduate Research Fellowship Program offers awards that support projects in duration of a summer term up to one semester in length. Fellowships can be awarded for up to two years for selected students, and the program is open to students in every major.
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