Dixon discovers a new type of cell death

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“At first, nobody believed you,” Scott Dixon said. “The first time I presented on ferroptosis at a cell death conference and used that word, there were audible groans in the audience.”

Yet scientists could one day induce ferroptosis in cancer, causing tumor cells to die, or halt it in Lou Gehrig’s disease, helping nerve cells survive.

Scott Dixon

For spearheading the identification of a form of iron-dependent cell death and detailing its regulation since then, Dixon received the 2023 Earl and Thressa Stadtman Young Scholar Award from the American Society for Biochemistry and Molecular Biology.

In a letter of nomination for Dixon, Brent Stockwell, a professor at Columbia University, wrote: “We have learned more from his work on an erastin-induced cell death mechanism in two years than we have. learned cumulatively…over the previous 11 years.”

Dixon wasn’t always decided on the science.

“I won’t pretend I had the junior chemistry kit,” he said. In fact, he didn’t get excited about lab work until his third or fourth year of undergrad. Experiments in a lab class are “often a canned thing that people have been doing for decades, and it can feel a bit unexciting,” he said.

“But then you listen to a graduate teaching assistant tell you what he does… how he draws on some of that foundational understanding to look at something really new… You can’t help but be excited .”

The words of the graduate students gripped him. “I realized that I would like to experience research in this way and really ask a question that no one else has asked and see what kind of answers we can get.”

Dixon distributed tools that activate or inhibit ferroptosis so that other scientists can study it themselves. “Anyone can test for this phenotype,” he said. “Then they can see, ‘Oh, wow. It’s happening here, and it’s happening here, and it’s happening here.'”

Bundling and shredding

Ferroptosis comes from the words “ferro”, which means iron, and “ptosis”, which means to fall (like the leaves of a tree).

Faced with such a death, the inside of a cell swells. Eventually, the membrane is “shredded,” Dixon said. It is fatal damage to lipids.

“If you had asked people in the 1990s if it was possible that there was some form of non-apoptotic cell death that was also regulated, the answer generally would have been no,” Dixon said.

By the 2010s, clues existed in the literature, he said. Junying Yuan’s work on necroptosis established the concept that there are non-apoptotic ways for cells to die that still require genetic and biochemical regulation.

“So that opened up the area wide enough for a lot of others, including ourselves, to go on a few years later and come up with additional mechanisms that weren’t apoptosis, or (were) distinct from necroptosis , and say, well, it’s not such a crazy idea that there would be a new mechanism.

Looking for examples of oxidation or loss of certain metabolites associated with cell death, Dixon found older papers describing similar phenotypes.

His reaction ? “Oh, that sounds a lot like ferroptosis,” Dixon said. In some cases, the work dates back decades, before people even realized that cell death is regulated.

“We just put the pieces together.”

Sometimes, when cells collapse, ideas come together.

For the most well-known type of cell death, apoptosis, “We’ve moved from having a fundamental understanding to translating that knowledge into treatments for people,” Dixon said; while for more recently discovered pathways, including ferroptosis, “we are in the middle of this process”.

At Discover BMB 2023, Dixon will present an update on the field of cell death.

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