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Pat Griffin

Toward New Treatments for Disease

Patrick Griffin’s scientific life, which involved a transition from the pharmaceutical and biotechnology industry to the academic world at the Scripps Florida campus over a decade ago, has always revolved around discovering new approaches towards treating disease. During his career, Griffin has been part of teams that have produced several drug candidates currently used as therapies.

Griffin was a key part of the Scripps Molecular Library Screening Center, which was developed to facilitate discovery of "proof-of-concept molecules" that could lead to new treatments.

“With our extensive basic research expertise coupled with a wide range of talents within our core resource centers, we can work synergistically on innovative projects in many disease areas and explore new methods of treating diseases that can help a host of patients,” Griffin says.

Opportunity for Innovation

“In the academic setting, our program is unique in terms of having all the components in one place,” he says. “We can attack an important biological problem using high-throughput screening, medicinal chemistry, structural biology, pharmacology, drug metabolism, proteomics and genomics. This comprehensive research-driven process facilitates finding therapeutic solutions to complex diseases, and doing this in the academic world allows us to focus on research that is patient-oriented rather than strictly profit-driven.

In the last few years, Griffin’s research has made deep inroads into several areas. These include uncovering some key features of a protein considered to be a master regulator of how the human body uses and stores energy, a discovery that could help in the design and development of new treatments for diabetes and obesity—and perhaps some cancers as well.

Griffin and his colleagues also developed an experimental compound with the capacity to significantly reduce joint inflammation in animal models of rheumatoid arthritis, an autoimmune disease that affects more than two million Americans.

More recently, Griffin identified a new therapeutic approach that, while still preliminary, could promote the development of new bone cells in patients suffering from bone loss. The research focused on that master regulator, a protein called PPARy, and its impact on stem cells derived from bone marrow (“mesenchymal stem cells”). Since these particular stem cells can develop into several different cell types —including fat, bone and cartilage—they have a number of potentially important therapeutic applications.

Griffin and his colleagues knew that a partial loss of the PPARy protein in an animal model increased bone formation. To mimic that effect, they designed a new compound that could repress the protein’s biological activity. The results showed that when human mesenchymal stem cells were treated with the new compound, there was a statistically significant increase in osteoblast formation, a cell type known to form bone. 

“We were surprised in the bone growth,” Griffin said. “We thought the effect would be neutral in cells but it actually promoted bone growth.” While research into the new compound is still ongoing, the bone growth effects have also been observed in animal models of obesity.

Solving Complex Problems

A protein chemist by training, Griffin spends a great deal of his laboratory time looking at target class proteins called nuclear receptors—using a technology called hydrogen/deuterium exchange mass spectrometry (HDX-MS) to examine complex protein dynamics.

HDX, a technology that Griffin and his colleagues have helped pioneer on the Jupiter campus, offers a way to gather difficult-to-obtain information about proteins. HDX is sensitive enough to provide accurate analysis of protein dynamics, which provides insight into function and is useful in solving complicated drug development problems.

“We’ve set the HDX technology bar very high with the ability to do rapid, in-depth statistical analysis,” says Griffin. “Many people who started partnering with others have eventually come to us because of what we can do at Scripps Florida with our HDX platform.” What Griffin and his group have done with HDX is to significantly shorten the time it takes to analyze data—data can be retrieved in seven hours and analyzed in half an hour. “Because of the advances in the platform, we can quickly find the statistically significant changes in receptor shape and dynamics, so we can actually start building models and designing better drugs,” Griffin said.

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“In the academic setting, our program is unique in terms of having all the components in one place,” says Professor Pat Griffin.