Adi Dubash earns $250,000 Grant from National Institutes of Health

When Adi Dubash, an associate professor of biology, started his lab in 2015, researchers had already shown that the complexes known as desmosomes were important for attaching cells to one another and giving tissues their structure. There was also evidence, though, from the work of others and Dubash’s work as a postdoctoral fellow at Northwestern University, that desmosomes were doing more than just sticking cells to each other like Velcro. It’s the desire to find out what else these structures are doing that’s at the core of the community of learning that’s grown in his lab and led to publications featuring undergraduate authors, presentations at scientific conferences, and now, an R15 grant from the National Institutes of Health.

“Desmosomes are complicated structures that classically were appreciated as the junction that provides tissues with mechanical integrity, but now more and more evidence is emerging that supports the roles” they play in how cells communicate with each other, explains Nicole Najor, an assistant professor of biology at University of Detroit Mercy who was a postdoc with Dubash at Northwestern University.

Sadie Hunter ’25 works in a molecular biology lab during summer research.

Cell communication, also called cell signaling, affects “how cells spread, move, interact with other cells,” she adds. “It is very exciting work, and even more exciting that he was recently funded by the R15, which will aim to uncover these questions all the while providing a unique research experience for the undergraduates at Furman University.”

To tease out the function of desmosomes in cell signaling and migration, Dubash has concentrated on a few of the individual protein components. In a study published in 2018, Dubash and four of his undergraduate researchers showed that the protein Desmoplakin, a part of the desmosome that is inside the cell, helps coordinate cellular migration.

“The broader context of that is, when you think of cells within a tumor, oftentimes what’s going to encourage cells to break off from that tumor and migrate to distant parts of the body [is] a loss of cell-to-cell attachment,” Dubash says. Understanding these attachments could therefore lead to better understanding of cancer metastasis.

Cell-to-cell attachment is dependent on the extracellular matrix—the scaffold of proteins and fibers that surround each cell—as well as on direct connections between cells. It’s known that desmosomes participate in both types of attachment, but how exactly they do that is still an open question. In 2021, Dubash’s team published a paper about Desmoglein-2, another protein component of the desmosome that spans from the inside to the outside of cells, crossing the cell membrane. They used microscopy and biochemistry to compare lines of cells that they grow in the lab: some with Desmoglein-2 intact and some without functioning Desmoglein-2.

The cells lacking Desmoglein-2 were much more likely to spread out than those with the functional protein. And the cells without Desmoglein-2 were super spreaders even when they were not attached to each other. The team showed that Desmoglein-2 interacts with an internal cell signaling pathway to influence cell spreading. The findings indicate that the part that Desmoglein-2 plays in cell spreading is independent of whether or not the cells are attached to other cells, adding support to the idea that desmosomes are much more than cellular Velcro.

In the proposal that earned Dubash the R15 grant, an award that supports small-scale research projects at educational institutions, he outlines the team’s future directions. Cell spreading, Dubash says, is really the first step in cellular migration. Once cells are fully spread out on the extracellular matrix, then they start to move by grabbing onto pieces of the extracellular matrix. Now that the researchers have shown that the cells without Desmoglein-2 spread more readily, they want to know whether extra spreading also leads to more migration and which signaling pathways are involved.

The project is already underway this summer in Dubash’s lab in the basement of the Townes Science Center. By August, his six undergraduate researchers are proficient cell biologists, microscopists and biochemists, ready to continue in the lab through the school year or to take their talents beyond Furman.

“I like to have each student have their own individual project, [and] they’re all working on a specific question related to the big umbrella topic,” Dubash says. “At first, the entirety of their focus is getting that technique down correctly. At the beginning, they’re not necessarily thinking very much about the big picture or the biology or the intellectual component of the project,” he says. “But as the summer progresses, I strive to make sure every student gets a clear framework of how to proceed through the scientific method.”