The findings from research by Prof. Irit Sagi, dean of the Feinberg Graduate School at Israel’s Weizmann Institute of Science, could have major implications in treating cancer, inflammation, infection and a number of autoimmune diseases.
Sagi, who teaches in Weizmann’s department of biological regulation, was in Montreal and Toronto last month to share the results of a study she’s been working on for the past two decades involving the examination of a group of proteins responsible for the progression of cancer, inflammation and many infectious diseases.
Addressing audiences of Weizmann donors, Sagi was the keynote speaker at parlour events in both cities, and she also spoke at a small event at the Israeli consul general’s home in Montreal as well as at the home of a private donor in Toronto.
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Sagi’s research, which is being referred to as groundbreaking and was recently featured in Nature magazine, involved looking at the structure and reactivity of various proteins, also called enzymes, that invade a body’s healthy tissues and cause damage to them.
In doing so, these enzymes contribute to a host of diseases. “Tissue damage is common to almost all invasive diseases, because the diseased cell infects the whole body through migration… the [invasive] protein paves a path for harmful cells to cross [a person’s] tissues and veins and invade almost any organ in the body,” Sagi said.
To figure out how to block a harmful enzyme, she explained, it’s first necessary to understand the enzyme’s structure and the way that it operates, both of which tend to be extremely complex.
Over the course of her research, her team has revealed, for example, the comprehensive structure of an enzyme called MMP9, which is known to be produced in metatastic cancer cells and in tissues attacked by autoimmune diseases.
Her research also included developing a precise method for tracking, in real time, the changes that occur in active enzymes.
Sagi said researchers are now using this method to develop a new generation of drugs.
Further, Sagi’s research team successfully designed certain molecules, known as therapeutic antibodies, which work to block invasive proteins responsible for tissue damage. “These molecules we’ve developed are antibodies, and the way they work is that they bind these very harmful enzymes in a specific conformation. That’s what makes them so unique – they target only the pathological [and not the healthy] form of the enzymes,” Sagi said.
She said her team will continue to investigate the workings of these invasive enzymes, as well as try to apply their findings to the development of therapeutic drugs that could, “fight the tissue damage in a number of autoimmune diseases.”
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They’re doing clinical trials to develop drugs for conditions such as Crohn’s, as well as other inflammatory bowel diseases and autism. “The research she’s done, such as her reversal of Crohn’s disease in mice, has grabbed the attention of some pharmaceutical companies,” said Lorie Blumer, a spokesperson for Weizmann Canada, a branch of an international network that supports the institute.
Sagi was born in Israel to a mother from Afghanistan and a father from Iran.
“At the Weizmann Institute, we have fantastic opportunities to do basic research, to work with superb students and colleagues and to access strong infrastructure,” she said. “These components really help to move fast to come up with, and execute, groundbreaking ideas.”