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Jeff Brodsky's basic science yields big results in cellular pathways

AAAS Fellow Jeff Brodsky has had a lasting impact on the study and understanding of cellular biology, but he is rather low-key about his contributions. (Photo: Jonathan Barnes)

It was a typical morning in the lab as Jeff Brodsky scanned a computer monitor, checking data from an imaging machine. Reading the info, he saw completely unexpected results. I'd better repeat this to make sure it's true, Brodsky thought.

"Understanding the results and what the next experiment would be was a knee-jerk response," he said.

Little did he realize it as a moment that would lead to changes in how doctors may be able to treat a specific class of diseases.

What Brodsky had uncovered was game-changing information on how proteins are folded and move through cells. Proteins that become misshapen and "misfolded" are connected to degenerative diseases such as cystic fibrosis. Brodsky was among the researchers who helped discover a cellular pathway that leads to misfolded proteins being degraded, known as the Endoplasmic Reticulum Associated Degradation (ERAD) pathway.

When he made the discovery, it was an "Aha" moment.

"I was doing a mundane experiment and thought the results also would be mundane but as soon as I saw them, I knew it would drive my research for years to come," he said. "The results immediately showed that degradation could not happen in the endoplasmic reticulum. "

Prior to that moment, the assumption always had been the opposite. A couple of years of additional research were needed before it was appreciated that diseases such as cystic fibrosis are connected to this process. Now it is known that more than 60 human diseases are linked to the ERAD pathway.

These days, Brodsky, a newly elected AAAS fellow, manages those working in his lab at the University of Pittsburgh as the Avinoff Professor of Biological Sciences, while also writing, researching, teaching and volunteering. His current research focuses on discovering how specific diseases are linked to the ERAD pathway and on identifying molecules that can affect the pathway, ultimately leading to treatments for the diseases.

His work days are long—a mix of meeting with people in the lab, reviewing literature, teaching, writing grants and manuscripts and handling administrative work. He also serves or has served on advisory boards for the Cystic Fibrosis Foundation, the National Institute of Health and the Dystonia Medical Research Foundation, as well as several companies and on the editorial boards of four scientific journals.

Brodsky has had a lasting impact on the study and understanding of cellular biology, but he is rather low-key about his contributions.

"Scientists will always say there's a huge amount of sweat that's important for good luck--and there's intuition," Brodsky said. "I started off working on a basic esoteric biological question. We were studying a simple biological question using yeast as a model organism—we weren't setting out to study disease. But understanding basic questions about cell biology is how you cure cancer and other diseases ... People are now taking drugs for altering diseases that are directly related to the ERAD pathway."

There's no doubt Brodsky has labored and been lucky, but his intuition might be a family trait, as is his interest in science.

Growing up in Chicago, he learned early off the patience needed to be a scientist, a notion absorbed from his physicist father, Merwyn Brodsky. Jeff Brodsky grew up as an ardent Chicago Cubs fan, which itself could be viewed as a series of lessons on patience. The team's checkered history was a life lesson the father pointed out to his son.

"My dad said being a Cubs fan is good preparation for science, because most of the times, things don't work out for you," Brodsky said, with a laugh.

Brodsky's patience may soon pay off. Already there are treatments for some classes of cystic fibrosis, and he expects more soon.

 "The next five years will see significant improvements in the ability to treat a wide proportion of those with CS," Brodsky said.

Representative Image Caption
AAAS Fellow Jeff Brodsky has had a lasting impact on the study and understanding of cellular biology, but he is rather low-key about his contributions. (Photo: Jonathan Barnes)
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