With this award, we have accomplished two main goals: 1) develop a better way to test new drugs in the laboratory and 2) help recruit young women to pursue careers in science. With regards the first goal, we developed an approach to evaluate drug penetration and metabolism that minimizes animal testing. When new drugs are developed, they need to be extensively evaluated before they can be used to treat people. Traditionally, drugs will be tested on animals, usually mice, to assess their properties in live cells. While this is still a necessary step, we have developed a cell culture approach that can be used prior to animal testing to determine if drugs will penetrate a mass of cells and if they will be metabolized by the cells. Only drugs that perform as expected with the cell masses are then tested on animals.

Our approach uses three-dimensional human cell cultures. These cells were previously donated by patients for scientific research and we use them to test the effects of new drugs. We grow the cells into three-dimensional structures that mimic human tumors. These structures are known as spheroids and, similar to a tumor, the cells inside the spheroid can differ substantially in their health and viability.  We can isolate different populations of the cells from the structure with a process known as serial trypsinization. The distinct cell populations are analyzed with a technique called mass spectrometry, where some of the molecules in the cell are weighed to determine their identity and abundance.  

In our new method, we are figuring out if new drugs work. To accomplish this goal, we use a combination of spheroids, serial trypsinization and mass spectrometry to determine where the drug goes in the cell mass (penetration) and how it is broken down in the cells (metabolism).  While this approach does not eliminate the need for animal testing, it is a viable precursor that helps to reduce the numbers of compounds that need to progress to animal models. Over the last six years, we have used this approach to evaluate many compounds. We started with FDA-approved compounds as we validated our methods, for example, irinotecan and doxorubicin. We have also used the approach to evaluate new compounds, including compounds from the laboratory of Bradley Smith at Notre Dame and more recently, from Dehua Pei’s laboratory at Ohio State. In some cases, the drugs have shown effective penetration and metabolism in the cell cultures and have moved onto animal testing and, for those that do not, their synthesis is being optimized in the laboratory.

For our second goal, help recruit young women to pursue careers in science, we have hosted Girl Scout troops in our lab over the last six years. The girls visit the lab for a day, perform experiments with my graduate students and learn about the scientific process. These visits have been a positive experience for my students and, as evidenced my surveys of the girls, the Girl Scouts too. During the course of the award, we have hosted four groups in our lab. A fifth group was scheduled to visit in May 2020, but that trip has been postponed due to the COVID pandemic. We will reschedule the visit once the situation improves.

Overall, with the generous funding from the NSF, we have successful completed the two goals for this project and look forward parlaying these results into additional discoveries. We are grateful for the support from the NSF.

Last Modified: 07/31/2020
Modified by: Amanda Hummon