The first thing you notice when you walk into the zebrafish facility at Sanford-Burnham is that it’s hot. Perhaps not Dallas in August hot, but balmy just the same.“Yes, but it’s dry,” says assistant professor Duc Dong, Ph.D., perhaps a little tongue-in-cheek.
Dr. Dong uses fish as a model organism to study disease, particularly diabetes. While he has experience with other animal models—earlier in his career he worked with Drosophila (fruit flies)—he found that fish are great models to study the pancreas and liver, which Drosophila don’t even have.
“Fish are an excellent model because of their fecundity and amendable genetics,” says Dr. Dong. “Also, they’re mostly transparent, so it’s easy to study their development; they’re in water and are highly permeable to small molecules (drugs) and 80 percent of the drugs that work in mammals also work in fish.”
The Dong laboratory is looking at the developmental biology behind the pancreas to find ways to regenerate insulin-producing beta cells.
“Usually in diabetes there are a few beta cells left,” says Dr. Dong. “One question is: How can we replenish their population in diabetics? If we understand the developmental biology, then we might be able to replicate it. Also, with an understanding of the regenerative pathway, we may have therapeutic targets where you add a drug or apply gene therapy to encourage the body to regenerate the cells.”
The laboratory is also trying to encourage pancreatic exocrine cells, which produce digestive enzymes, to transdifferentiate into beta cells. “They come from the same precursors,” says Dr. Dong. “We found that the regulation of a particular gene helps decide the fate of these precursors. We hope that, by manipulating this gene in diabetics, we can help make more beta cells.”
His lab recently found that several of the adult onset diabetes genes have a common developmental function in regulating a key diabetes genetic pathway. These findings help to explain the etiology of diabetes. But diabetes is only part of the story. Dr. Dong feels that other aspects of human health could benefit from a better understanding of developmental biology. He notes that many diseases are caused by dysfunctional developmental pathways. He is also interested in pancreatic and colon cancers and is working to develop a zebrafish model for these diseases.
He notes that fish also fill the spot between cells and mice for drug screens. “We want to find drugs that specifically kill cancer cells in fish,” says Dr. Dong. “They work well for these types of studies because you can test drugs faster than you could in a mouse model but are more stringent than testing only in cells. We expect to have fewer false positives.”
This rapidity may be the ultimate reason why Dr. Dong has gravitated towards zebrafish. “In the fish model, the pace of the science is fast. I like the instant gratification.”