Little stripes, big answers

Unlocking the mysteries of human diseases with the help of a little fish

One of the lesser-known dwellings on the University of Miami campus is a place referred to as the “Zebrafish Hilton” by facility manager, Ricardo Cepeda, whimsically listed in the directory as the “local fish whisperer.”

A former literature teacher in Colombia, Cepeda keeps close watch on the nearly 6,000 zebrafish living in the Zebrafish Core Facility, the site of cutting-edge research used by faculty and students to model human genetics and disease, from Parkinson’s and autism to peripheral neuropathy.

Known scientifically as Danio rerio, zebrafish are a striped species of fish native to Southeast Asia. They grow to only about an inch and a half in length. But that small size, which makes the entire fish easier to view with magnification, is just one of its many advantages for research.

Zebrafish eggs and young are translucent, which makes for easy observation of their internal organs. They mature quickly, developing as much in a day as a human embryo does in a month. And as vertebrates, they have physiology similar to humans with comparable nervous system, muscle, blood, kidney and eye structures.

“We keep thousands and thousands of adults and they live for years in the Zebrafish Hilton,” says Julia Dallman, Zebrafish Core Facility director and associate professor of biology. In addition to overseeing operations at the facility, Dallman also studies zebrafish. Her main area of research is autism, using genome editing technologies to study some of the hundreds of genes linked to the condition.

In terms of genetics, zebrafish have a structure remarkably close to humans and share 70 percent of the same genes (as well as more than 80 percent of the genes linked to human diseases). They’re also cheaper to acquire and use than mice, in part because you can get a whole bunch of zebrafish very quickly thanks to their prolific reproductive cycle and the ease of genetic manipulations.

“Zebrafish females produce up to 300 eggs at a time, once a week,” says Dallman, who also started the Department of Biology’s zebrafish colony with 40 “pioneers” she brought from New York after joining UM in 2007. “We’re using an animal model to get to the underlying mechanisms of disruption of genes. It’s not autism per se that we’re addressing so much as comorbidities common to autism, like seizures or gastrointestinal distress. A lot of other conditions are also associated with gastrointestinal distress, like Parkinson’s. It can be an early indicator of nervous-system trouble.”

Another Zebrafish Core Facility tenant is Associate Professor Sandra Rieger, who primarily studies neuropathy and appendage regeneration in the Department of Biology. Zebrafish is one of the few vertebrates with robust regenerative abilities. Rieger’s team is studying the nervous system’s role in fin regeneration, cutting them off and watching them grow back.

Using zebrafish, Rieger is studying the use of possible inhibitors to prevent chemotherapy and diabetes-related nerve degeneration. Initial results have been promising with zebrafish as well as rodents, so much so that she has been starting up a company to develop a molecule for testing and eventual treatment in humans. That’s years off, but it can’t happen soon enough.

“Chemotherapy-induced and diabetic neuropathy are very relevant topics, affecting approximately 15.5 million people in the US” Rieger says. “Patients frequently email me and have hope in my research as a new approach that could potentially treat them. Right now, there is no treatment, so people are desperate and living with pain as well as numbness and loss of balance. Pain is the most common and terrible symptom, and pain medicines can be addictive. I hope to find treatments for them.”

As for neuropathy, it’s a degenerative nerve condition that commonly manifests as pain or numbness in the hands and feet. Neuropathy is associated with a wide range of conditions and causes besides chemotherapy and diabetes, including environmental toxins, alcohol, trauma, and antibiotics. It’s also a common side effect of the chemotherapy drugs used to treat cancer, which is where Rieger’s research comes in.

“From an evolutionary standpoint, regeneration occurs more frequently in invertebrates and lower vertebrates and has been lost in the mammalian lineage throughout evolution,” says Miguel A. Portales Guemes, one of Rieger’s student collaborators. “We want to understand why humans do not regenerate their tissues as well, and if there is a way to supplement or reactivate that since we have the same genes as zebrafish need to regenerate. If we find the mystery behind growing back tissues, maybe we can improve the healing process in people.”