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“Kracking” the KRAS code

A recent study led by Professor of Obstetrics, Gynecology, and Reproductive Science, Hugh Taylor, at the Yale School of Medicine has identified the first genetic marker for endometriosis, an invasive disease characterized by infertility and chronic pelvic pain that afflicts 70 million women worldwide.

While mouse models have demonstrated a causal link between the overexpression of KRAS, a proto-oncogene involved in tissue signaling, and the development of endometriosis, a genetic basis had never been implicated in humans before this discovery.

With his team, Taylor, an infertility specialist who has studied the development and function of the uterus for twenty years, identified how a variant in a regulatory region of KRAS leads to the gene’s overexpression and an increased likelihood of developing a genetic form of the disease. The researchers screened 132 women with endometriosis and found that 31 percent carried the variant as opposed to 5.8 percent in the general population. Additionally, endometriosis patients with this marker tended to develop an invasive type of the disease that was more likely to lead to infertility.

Pictures of human endometrial tissue with the KRAS variant (right) and the wild-type (left). Courtesy of ProfessorTaylor.

The team’s discovery will allow physicians to develop novel treatments to target the inhibition of this genetic pathway. Additionally, genetic testing may become an effective tool to prevent development of the disease in individuals with a family history of the condition.

Taylor attributes his success to the collaborative environment that fostered discussions with fellow professors Joanne Weidhass and Frank Slack, who discovered the KRAS variant and its effects on gene expression in ovarian cancer. “This cooperation between physicians, physician-scientists, and scientists,” Taylor states, “is the type of interaction that leads to success.”