New Pitt Center Will Study Diseases Linked to Misshapen Proteins

Most fatal long-term disorders, from Alzheimer’s to cystic fibrosis, result from protein breakdown

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Through a comprehensive understanding of how to fix protein architecture when it goes awry, University of Pittsburgh researchers will be positioned to improve prognoses for millions of people with debilitating diseases.

The Center for Protein Conformational Diseases, set to launch in April, is one of only two such centers in the United States.

The center will bring together faculty members across 15 academic departments as well as nine other Pitt centers and researchers from nearby Duquesne University to hunt for breakthroughs in protein breakdown. “The center was a way to codify the research relationships we’ve already been having for many years,” says Director Jeffrey Brodsky, a molecular biologist and professor in Pitt’s Department of Biological Sciences.

Brodsky likens the protein problems to the real estate market.

Consider a neighborhood of houses spanning all styles: Victorians, Georgians, classical, modern. All are distinct and comfortably lived in. But then a few families move away, and their homes are left vacant. Over time, the vacant houses become derelict, and the entire neighborhood’s property values depreciate.

So, too, in the ecosystem of the human body, Brodsky says. Approximately 23,000 proteins, each with its own structure and function, are responsible for keeping us healthy by sustaining our systems. Biochemical maintenance crews, which include a family of proteins appropriately known as “molecular chaperones,” help keep a neighborhood watch. “If a specific protein becomes misshapen, basically a cellular bulldozer wipes out that house. Typically that’s a good thing, so that cellular property values don’t fall.”

But as we age “the cellular bulldozer driver starts to take longer holidays,” Brodsky says. Misshapen proteins accumulate and stop performing their essential functions. The result is any number of ailments, ranging from cystic fibrosis, Alzheimer’s disease and Parkinson’s disease to some types of kidney and liver disease and certain cancers.

“Ultimately, if we survive other bad things that can happen earlier in life,” Brodsky says, “eventually we will die from one of these diseases.”

The project has been approved by both Dean N. John Cooper, Kenneth P. Dietrich School of Arts and Sciences, and Arthur S. Levine, senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of the School of Medicine.

“Researchers in Pitt’s School of Medicine and Dietrich School of Arts and Sciences have a long history of collaborative investigations into the biological mechanisms underlying these diseases, as well as their clinical manifestations,” Levine says. “It’s very exciting that we now have a formal entity to support and accelerate these activities under the leadership of Dr. Brodsky, who is nationally recognized as a leading investigator of the basic biology of conformational diseases.”