Fishing for Insights into Human Disease

January 18, 2024
Caghan Kizil holds a tank of zebrafish he uses to understand how fish repair their brains and if the same processes can be turned on in humans. Photo from the Crown Awards Gala video.

Caghan Kizil holds a tank of zebrafish he uses to understand how fish repair their brains and if the same processes can be turned on in humans. Photo from the Crown Awards Gala video.

Over the years, zebrafish (and to a lesser extent killifish) have become an important experimental model in biomedical research, thanks to their genetic similarity to humans, transparent embryos, rapid development, and regenerative abilities, among other features. Columbia researchers are using these finned wonders to gain insights into human health and disease. Caghan Kizil, PhD, MSc, Associate Professor of Neurological Sciences in Neurology and in the Taub Institute, uses zebrafish in his research on Alzheimer's disease. [read more about how other Columbia researchers are using zebrafish in their work]

Can zebrafish teach us how to regenerate neurons?

No one would argue that zebrafish, whose brains are the size of a sesame seed, are smarter than humans. But these tiny aquatic animals can do a few tricks that humans cannot, such as growing scores of new brain neurons in response to neurological pathologies such as Alzheimer’s disease or injury, even well into adulthood. In contrast, once past childhood, humans can manage to regenerate only a smattering of neurons, a rate that declines even more with disease.

Using zebrafish as a model organism, Caghan Kizil, PhD, associate professor of neurological sciences (in neurology and in the Taub Institute) at the Vagelos College of Physicians and Surgeons, is gaining new insights into the molecular mechanisms that underlie neuronal regeneration, or neurogenesis.

“The beauty of zebrafish is that we can get human-relevant experimental results in weeks instead of months or years with other animal models,” adds Kizil. “We can even get these fish to perform memory tests to investigate the cognitive consequences of therapeutic interventions for neurological diseases.”

Thus far, Kizil’s studies have revealed a key molecule (nerve growth factor receptor) that controls nerve regeneration in zebrafish. The same molecule appears to be active in humans during early development but not in Alzheimer’s patients.

“If we could kickstart neurogenesis in humans, we might be able to slow the progression of Alzheimer’s by enhancing the brain’s resilience,” says Kizil. His team has already identified two potential targets for drug therapy. The researchers are designing compounds to selectively hit those targets, which they will evaluate in zebrafish.

Source: CUIMC Newsroom