Scientist to use $200K research grant to seek scleroderma cause

The National Scleroderma Foundation has awarded a $200,000 research grant to a University of Minnesota scientist to study how immune system responses drive the emergence of scleroderma — the cause of which remains unknown.

The funding for researcher Rafael Contreras-Galindo, PhD, comes in the form of the two-year Marta Marx Fund for the Eradication of Scleroderma Award, given to scientists submitting the second-highest scoring research proposal to the foundation each year.

The project will be titled, “Centromeres, Chromosome Instability and cGAS-STING Activation in Scleroderma Fibrosis.”

“Identifying the cause of scleroderma is the main goal of this study,” Contreras-Galindo, assistant professor at the University of Minnesota’s The Hormel Institute, said in a university press release.

Scleroderma is an autoimmune disease that arises when the body’s immune system becomes overactive and attacks its own tissues, in this case, causing inflammation and damage to connective tissue.

In response, the cells overproduce collagen — a connective tissue protein — leading to scar tissue buildup that hardens and tightens connective tissues in the skin or other organs.

While the results are known, the mechanisms underlying this process haven’t been fully worked out. Contreras-Galindo’s team will specifically examine the potential role of centromere dysfunction in triggering these harmful immune responses.

Chromosomes, thread-like structures where DNA is packaged, consist of two identical halves. When a cell divides and replicates, these two halves split apart, ensuring that each new cell has the same genetic information as its parent.

Centromeres sit between these two halves, holding them together and facilitating their split during cell division. If that process is defective, chromosomes become unstable and certain immune pathways can be triggered in response.

With his team, Contreras-Galindo found that people with scleroderma had signs of centromere defects in their skin cells not seen in healthy people. Findings from their work were published in a study in the journal Nature Communications

Data also indicated that an immune pathway called cGAS-STING was activated in SSc cells, which the researchers believe was triggered by the chromosomal abnormalities that were found.

A potential treatment strategy is using therapies to weaken this immune signal pathway.

With the ongoing project, the team will further explore the role of cGAS-STING in scleroderma. They believe that its overactivation might drive inflammation and blood vessel injury, in addition to causing scleroderma cells to overgrow and form scar tissue.

“A potential treatment strategy is using therapies to weaken this immune signal pathway,” Contreras-Galindo said. “This could slow down the production of scleroderma cells, leading to less scar tissue being produced.”

Activation of the cGAS-STING pathway also has been implicated in a number of other inflammatory, autoimmune and neurodegenerative diseases, including lupus, rheumatoid arthritis, and amyotrophic lateral sclerosis.