UC San Diego Biologist and Collaborators Receive $1 Million Keck Award

That discovery led to more exploration of where this inflammation was coming from and whether it was somehow important to avian skeletal development. It turned out that it was, a finding that was published in the journal PNAS last year. Now, Rashid, Kim Cooper of the University of California San Diego and colleagues at Clemson University have been awarded a prestigious $1 million grant from the W.M. Keck Foundation to continue studying the phenomenon, which has implications for health and skeletal development in humans.

In their earlier work, the researchers discovered that when chickens were treated with anti-inflammatory drugs, the evolutionarily derived bone fusion was halted — an astounding impact for a drug to have on an evolutionary mechanism developed over hundreds of millions of years. If similar inhibition of developmental bone fusion were to be observed in humans, Rashid said, they could raise questions about the impact of corticosteroids or other anti-inflammatories on skeletal growth, particularly in children.

Cooper’s research expertise in skeletal development will bridge the investigation from birds to mammals. Her laboratory at UC San Diego’s School of Biological Sciences focuses on developmental and evolutionary processes using laboratory mice and jerboas, three-toed relatives of the mouse with elongated hind limbs.

“Inflammation is traditionally not thought of in a natural constructive process,” said Cooper, a professor in the Department of Cell and Developmental Biology. “During this project we will use bone fusions found in bipedal jerboas to study how these inflammation questions translate in mammals.”

Like the bird study, part of the studies at UC San Diego will involve treating the animals with anti-inflammatory drugs to evaluate whether they prevent immune cell infiltration and whether these cells are required for bone fusion.

The Keck award will fund three years of continued research, which will include explorations of non-pathological inflammation in mammals. The funding will support a research scientist and both undergraduate and graduate student scientists.

“In order to make this applicable to humans and human medicine, we needed to move to mammals and show that this is a universal mechanism,” Rashid said. “So, this grant is to start looking at mammals to build off what we started in birds.”

The fusion of separate bones into a single bone is common in skeletal development, Rashid said, especially in the sacrum and in areas around growth plates such as the arms and legs in humans. Bone fusion in those areas, which are called epiphyseal plates, is a sign of skeletal maturity.

If that fusion is induced through inflammation, then treatment with anti-inflammatory drugs, as is common with conditions such as asthma, could potentially inhibit proper skeletal growth.

“We're still learning which fusions are susceptible to anti-inflammatory drugs,” Rashid said. “This is really important to know, especially for kids who are on long-term corticosteroids and other anti-inflammatory drugs. We need to know what's happening with their skeletons.”

The team will also explore a concept called necroptosis, which is a form of cell death in living bodies. Because necroptosis is often highly correlated with diseases like bone cancer and ankylosing spondylitis, which results in detrimental fusion of the vertebrae in the spine, Rashid said that identifying the connection between necroptosis and inflammation could lead to new avenues of medical research.

— Adapted from an MSU News Service article

About the W. M. Keck Foundation

The W. M. Keck Foundation was established in 1954 in Los Angeles by William Myron Keck, founder of The Superior Oil Company.  One of the nation’s largest philanthropic organizations, the W. M. Keck Foundation supports outstanding science, engineering and medical research.  The Foundation also supports undergraduate education and maintains a program within Southern California to support arts and culture, education, health and community service projects.