Dr. Zachary Walls has found a way to treat cancer from the inside out.

Walls, who joined ETSU in the fall of 2011 after his postdoctoral time at University of Michigan, has been focused on developing solutions for subcellular drug targeting since the spring of 2012.

For those unfamiliar with this subject, Walls explained what he is working on in a simpler fashion.

“Essentially, you’ve got a lot of drugs; most of them are targeted at molecules outside of the cell,” Walls said. “There’s this whole other world of targets inside of a cell, and it’s really hard to get drugs inside of the cell. Most cells are deigned to reject things, so we design ways to get those drugs inside and into the right compartment where they can interact with the target that will have some impact on the pathophysiology of the disease.”

The concept of subcellular drug targeting has been around since the late ’60s and early ’70s, but Walls and his colleagues seek to make this concept an accessible reality.

During this time, scientists were looking in nature to find bacteria that produced antimicrobial compounds, which Walls described as complex molecules that cannot be synthesized ourselves. Scientists discovered a complex molecule they named doxorubicin, which was found to have many cancer fighting properties, but it was also found to kill healthy cells, especially heart tissue.

Twenty years later, doxorubicin was packaged in liposomes, which was the first step to subcellular drug targeting. The liposome is likened to a host of balloons, which gets released into the body and find its way into the damaged, leaky cancer cells. The liposomes are a way to minimize damage to the healthy tissue, since it cannot penetrate it.

Scientists were surprised to see that while the damage and side-effects were lesser, repackaging into the liposomes did not treat the cancer any better. This is where Walls’ research comes in to play.

“I’ve been surprised to find that my original hypothesis I started four years ago was correct,” Walls said.

Walls realized that if they expressed this protein, listeriolysin O, it could be packaged along with the drug, and that will allow the drug to escape.

In January of 2016, Walls and his colleagues published their findings with a paper entitled, “Liposomal Coencapsulation of Doxorubicin with Listeriolysin O Increases Potency via Subcellular Targeting.”

This study has found success and will most likely affect many different drugs and diseases in the near future.

 

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