UMass Amherst Team Develops Methods to Reprogram and Repair Cells

Researchers at the University of Massachusetts Amherst have devised two complementary strategies that could have therapeutic potential in cancer and immune diseases. Their work, published in the Journal of the American Cancer Society, explores ways to either eliminate or repair malfunctioning proteins on the surface of cells—key problems that underlie many diseases. “The recent work my group has done addresses a long-term challenge in protein therapy,” says Sankaran “Thai” Thayumanavan, senior author of the study. “We have built ‘platform technologies’ focused on fighting cancer, but which can also be used to treat all sorts of cellular diseases.”

A cell’s surface is densely covered with proteins that connect its internal operations to external signals. When these proteins malfunction, they can instruct cells to divide uncontrollably or hide from immune detection. Even though only a quarter of all human proteins reside on the cell membrane, nearly half of existing drugs target them. The UMass Amherst team has pursued new approaches to work directly with these surface proteins through two distinct but related techniques. 

The first method, called PolyTAC, aims to destroy damaged membrane proteins. Lead authors Ryan Lu and Jithu Krishna found that applying physical pressure at precise points on the cell surface can activate the cell’s own disposal system. “If you think of the cell surface as a balloon,” explains Krishna, “we discovered that when you physically press the balloon, making a dimple, in just the right spot, that deformation triggers the cell’s internalization machinery.” The PolyTAC combines an antibody that recognizes the problem protein with a polymer that presses into the membrane, prompting the cell to pull in and break down the defective protein. As Lu describes, “Our PolyTAC zeroes in on the specific weed and routes it to the shredder machinery in the cell to destroy it.”

The second approach, developed by Shuai Gong and Jingyi Qiu, repairs rather than destroys. Their Artificial Cell-Derived Vesicle (ACDV) system delivers functional proteins directly to the cell membrane, effectively restoring healthy behavior. “This allows for personalized therapies,” Qiu says. The ACDV platform enables scientists to replace faulty proteins with correctly functioning ones, potentially reprogramming diseased cells into normal ones. As Thayumanavan concludes, “By transforming the display of proteins on the cell’s surface, we can custom-tailor the way the cell functions.”