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Creative Minds: Of Arsenic and Misfolded Proteins

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John Hanna

John Hanna

Taking out the trash is a must in every household. Inside our cells, it’s also essential because if defective proteins are not properly disposed of, they can accumulate and make a mess of the cell’s inner workings, leading to health problems.

John Hanna, a physician-scientist at Brigham and Women’s Hospital, Boston, is on a quest to study the cell’s trash disposal system in greater detail. In particular, this 2014 NIH Director’s Early Independence awardee wants to learn more about how cells identify proteins that need to be discarded, how such proteins are steered towards the molecular garbage can, and how, when the process breaks down, neurodegenerative conditions, cancers, and other diseases can arise.

That’s a complex challenge, so Hanna will start by zeroing in on one particular component of cellular waste management—the component that clears out proteins damaged by arsenic. Although arsenic is notorious for being the poison of choice in countless true crime shows and mystery novels, this semi-metallic element is found naturally in soil, water, air, and some foods.


Of Mice, Men, and Medicine

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Photo of someone holding the lab on a chip device next to a photo of two laboratory mice

Will a chip challenge the mouse?
Source: Wyss Institute and Bill Branson, NIH

The humble laboratory mouse has taught us a phenomenal amount about embryonic development, disease, and evolution. And, for decades, the pharmaceutical industry has relied on these critters to test the safety and efficacy of new drug candidates. If it works in mice, so we thought, it should work in humans. But when it comes to molecules designed to target a sepsis-like condition, 150 drugs that successfully treated this condition in mice later failed in human clinical trials—a heartbreaking loss of decades of research and billions of dollars. A new NIH-funded study [1] reveals why.