Hardy’s research is part of a coordinated effort through the campus’s new Institute for Applied Life Sciences (IALS), funded largely with $95 million from the Massachusetts Life Sciences Center, which is focused on taking fundamental research in the life sciences and moving it more quickly to application. In her research, Hardy focuses on tiny proteins—small elements of the larger human system.
“We are working on the proteins that come from humans so the discoveries we make are directly relevant to human disease,” says Hardy.
Cell death, Hardy explains, can be good or bad depending on the context. In cases of cancer, cell death is a necessary part of the solution—the body senses that the cells are damaged and triggers apoptosis. In cases of Alzheimer’s and neurodegenerative disorders, however, the opposite is true. These diseases trigger unwanted apoptosis, killing necessary cells instead. Much remains unknown about the mechanisms for cell death, which is why Hardy and the team are studying caspases. By closely examining the structures of these proteins, Hardy is investigating how modulating their role in apoptosis could impact human health.
“You can see atom by atom what that protein looks like, which is really useful if you want to make a drug because you know precisely what your target looks like,” says Hardy.
Hardy explains that the therapeutic “bullet” that will block caspase-6 must be strategically designed to not block caspase-3 (and other caspases), or it will prevent the body from killing off abnormal cells. The fact that various caspases play various roles actually allows Hardy’s team to harness caspase function for a number of different outcomes. When caspase-3 is activated, it triggers apoptosis and surrounding cells commit suicide. Hardy and the team are working with chemists Vincent Rotello and Sankaran “Thai” Thayumanavan on methods to utilize the trigger by delivering caspase-3 into cancer cells. In these applications, caspase-3 can act as a drug that kills cancer cells without collateral damage to healthy cells. Thayumanavan and his team have already developed a nanogel capable of delivering therapeutics to targeted cells, and the Rotello group has developed nanoparticles that can transport caspases and other proteins. Because cancer only proliferates when cancer cells evolve to evade apoptosis, the delivery of caspase-3 could be a novel cure.
Inspired by their work to find new ways to inhibit caspases, one of Hardy’s graduate students, Muslum Yildiz, has shown that he can alter the structure of dengue virus protease—the virus responsible for ‘bone-break fever.’ The deadly virus is a growing concern in tropical regions, and has recently spread through mosquitos to North America. Yildiz has shown how inhibitors that lock the protease into a new conformation prevent enzyme activity and could prevent infection.
The Council for International Exchange of Scholars recently awarded Hardy a Fulbright Scholarship to further her work on Alzheimer’s research with collaborators in Tokyo and Paris. In her research abroad, Hardy will incorporate the latest developments in nuclear magnetic resonance (NMR) spectroscopy, a technique critically important to her research.
Hardy says she is excited to return to this game-changing equipment and eager to use a one-of-a-kind high-throughput circular dichroism spectrometer to advance her research.
“There are a lot of ways that this investment will change the kinds of experiments we do and the speed with which we can do them. I foresee it being a nucleating point for other organizations to come here…to see us as the ‘go-to place for understanding the interplay between structure and drug delivery,’” Hardy says.
Amanda Drane '12
With the Institute for Applied Life Sciences and new state-of-the-art equipment, Hardy envisions the campus serving as a "nucleating point" to understanding the interplay between structure and drug delivery.