dr jarvis - path to a cure

Researchers on the Path to a Cure – Spotlight on Dr. James Jarvis

“Why did my child get arthritis?” This parent-driven question is at the heart of Dr. Jim Jarvis’s juvenile idiopathic arthritis (JIA) Arthritis Foundation-funded project, “Interplay between genetics and epigenetics in polyarticular JIA”.

“This is less about an illness driven by inherited genes and more about how the environment affects gene expression,” explained Dr. Jarvis. “It’s been shown that only about 30 percent of the risk for developing JIA can be attributed to gene variations.”

Epigenetics looks at the ways that genes and the environment interact and effect DNA and DNA expression.  This project is based on the idea that JIA develops because specialized white blood cells suffer changes due to gene-environment interactions that hinders the cell’s ability to regulate and coordinate DNA expression related to inflammatory response.

How does this work? Imagine a Slinky – you know, that toy so many kids have played with since the 1940s. The Slinky represents DNA structure. According to Dr. Jarvis, genetic and epigenetic changes determine how open or closed the Slinky becomes in different places.  If the Slinky is open, it’s easier for genes to turn on.  If it’s closed, it becomes more difficult to turn genes on.

The genome (cell’s DNA) can sense the environment and respond by changing which genes are turned on or off. Interestingly, the environmentally-caused changes in DNA may occur generations before the changes are expressed. For instance, it has been shown with mice that a traumatic event associated with certain smells can cause cowering in response to the smell for several generations of mice (even in those who are only exposed to the smell and no trauma). Or, as Dr. Jarvis explained, “The Mohawk nation has a saying that the harms inflicted on the Mother can be felt for at least 7 generations.”

Even subtle changes in which genes are turned on or off can disrupt the timing and coordination of cell processes, leading to chronic inflammation.

To explore gene-environment interactions, Dr. Jarvis and his team will compare genetic data from the specialized white blood cells of 30 children with newly diagnosed polyarticular JIA to similar data from 30 healthy children. The team has recruited and begun testing samples from about half of the planned group. While the study is still in its early stages, Dr. Jarvis said that preliminary data is promising: “So far, we’re finding that the DNA structure in the JIA patients is open and closed in places it shouldn’t be.  It also seems that treatment is helping the structure to become more normal. This is really good to see.”

“This study is giving us a springboard for not only understanding the basic mechanisms and treatment responses for JIA, but also for understanding the link between genes and the environment,” explained Dr. Jarvis. “It may provide another link to the Adverse Childhood Experience Studies that showed an increased risk of developing diseases like lupus and rheumatoid arthritis in adulthood, based on traumatic events in childhood. It may also help explain why JIA is 5 times more common in the native American population than the general population. Chronic, repetitive trauma and social marginalization over generations may contribute to the subtle changes that trigger this disease.”

Dr. Jarvis is a clinical professor, specializing in pediatric rheumatology at the University at Buffalo’s Jacobs School of Medicine and Biomedical Sciences Department of Pediatrics.  He is the recipient of an Arthritis Foundation 2016 Delivering on Discovery 2‑year award.

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