University of South Florida

Chad Dickey studies key role of chaperone proteins in Alzheimer’s, other diseases

Breathing, talking walking, remembering…. All these functions are coordinated by thousands of proteins out on the front lines keeping cells alive, healthy and working normally.  They are helped by molecules called chaperones that play a supervisory role in ensuring proteins are folded into their correct shapes. When something goes awry with the chaperones and proteins are misfolded, the good proteins may turn bad.

In his laboratory at the USF Health Byrd Alzheimer’s Institute, Chad Dickey, PhD, associate professor of molecular medicine and psychiatry and a research scientist at James A. Haley Veterans’ Hospital, leads a team studying chaperone proteins. The aim is to find ways to target these industrious assistants to treat neurodegenerative diseases known as tauopathies.  Abnormal accumulation of tau, a hallmark of protein associated with Alzheimer’s disease, is a feature of more than a dozen other disorders associated with loss of memory and movement, including progressive supranuclear palsy and Parkinson’s disease dementia.

Dr. Chad Dickey and team at the Bryd Alzheimer's Institute

USF Health Morsani College of Medicine neuroscientist Chad Dickey, PhD, with monitor displaying neurons.

The USF lab and others have begun to show that many diseases, inflammatory and cardiovascular as well as neurological, are in some way influenced by chaperones.

Last year, Dr. Dickey received two new R01 grants from the National Institutes of Health to help further USF’s chaperone protein research.

The first award — a five-year $1.95 million grant from the National Institute of Mental Health — will investigate how upregulation of the protein FKBP51 coordinates the brain’s response to stress.   Previous research by Dr. Dickey, published in The Journal of Clinical Investigation, showed that the age-related rise in levels of the stress protein FKBP51 usurps the beneficial effect of the stress-related protein’s chaperone partner Hsp90, thereby creating an environment that promotes tau toxicity and speeds the progression of Alzheimer’s disease.

The second award – a four-year, $1.74 million grant from the National Eye Institute – will be used to validate and improve upon a new specific inhibitor of the chaperone Grp94.  The Grp94 inhibitor, developed by Dr. Dickey’s team, accelerates the clearance of the genetically defective-protein myocilin known to cause the eye disease glaucoma.  Previous studies by the USF researchers, published in The Journal of Biological Chemistry and Human Molecular Genetics, found that Grp94 can interfere with the removal of the myocilin from cells and suggested that the chaperone offers a new target to treat some hereditary cases of glaucoma, a leading cause of blindness.

“There are still many unanswered questions about how chaperones work and fit into the protein-folding puzzle,” Dr. Dickey said. “But they certainly represent a lot of potential targets, and it’s our goal for USF to lead drug development efforts in the chaperone field for neurodegenerative diseases.”

Dr. Chad Dickey and team at the Bryd Alzheimer's Institute

Dr. Dickey and his team in one of their laboratories at the USF Health Byrd Alzheimer’s Institute.

Dr. Dickey joined USF Health as a faculty member in 2006 from the Mayo Clinic in Jacksonville, where he was an assistant professor of neuroscience.  He completed his post-doctoral training at Mayo under the direction of Dr. Michael Hutton, an expert in the field of Alzheimer’s disease genetics. He received his PhD in neuroscience from USF in 2004.

Dr. Dickey has authored or co-authored papers in more than 75 peer-reviewed journals, serves on the editorial board of Biochemical Journal and several other journals, and is a standing member of the NIH’s Drug Discovery for the Nervous System study section. He is a scientific advisory board member of the American Federation for Aging Research (AFAR) new investigator in Alzheimer’s disease program.

Photos by Eric Younghans, USF Health Communications

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