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Mike ForresterFishing for answers – and a cure – to leukemia “Zebrafish are the wave of the future for cancer research,” says Mike Forrester, a Ph.D. candidate working with Dr. Jason Berman in the Department of Microbiology and Immunology at Dalhousie University. Mike is using an animal model of high-risk leukemia to study how a gene mutation affects the growth of blood cells.

“We want to understand how this gene mutation changes blood cells into leukemia cells, and we want to find a new drug that specifically combats this high-risk gene mutation, because traditional chemotherapy drugs are not effective against high-risk leukemia,” he explains.

Instead of using mice to test these new drugs – a complex library of thousands of chemicals – Mike uses zebrafish. His work is going, er, swimmingly.

“Our research team believes it is the zebra fish and not the mouse that will quickly allow us to discover newer, better and safer drugs to treat human blood cancers.”

Zebrafish, which are used to study many cancers, have several advantages over mice. First, notes Mike, “In comparison with zebrafish, mice are bigger, more complex and very expensive.”

Zebrafish are minnows like those used as bait for fishing. “Because a mouse is roughly the size of a household light bulb, and a zebrafish is actually smaller than a triple-A battery, we can use many more of them to charge our research,” says Mike.

Mike is conducting his studies at the IWK Health Centre in the Berman Zebrafish lab, where there are 2,000 zebra fish. The same number of mice would require a much, much larger facility.

Mice also also carry a significantly larger price tag. “It costs $2,500 per mouse per year to do research,” says Mike. “Each zebrafish costs about $25 a year. That’s a big difference.”

Another readily apparent difference lies in the make-up of the zebrafish. “We can actually see through their skin,” notes Mike. “This is especially helpful for studying blood cancers.  It allows us to watch where the cancer cells are travelling through the body and how they grow and multiply, without having to cut the animal open and cause undue harm.”

Zebrafish are also a strong comparator for cancer in humans. “There are a lot of similarities at both the genetic and the molecular level between fish and humans,” explains Mike. “Fish have very similar blood cells to humans.”

The leukemia in the zebrafish Mike is studying is very similar to that found in people, he adds, noting that there are more than 30,000 chemicals available for testing, something that would simply not be possible using mice.

To date, Mike has discovered that the high-risk gene mutation he is exploring changes the delicate balance of blood cells in the body.  “Our mutant zebrafish have higher numbers of white blood cells and lower numbers of red blood cells.  They are also resistant to traditional chemotherapy, similar to human cancer patients that possess this high-risk mutation,” he says.

“We hope that this research will eventually impact on patient care, that is the ultimate goal of our work in the Berman lab,” he adds.  “We will increase the likelihood of this happening if we can discover a new drug that combats the high-risk gene mutation. In an 'ideal world,' this whole process might take 10 to 12 years until the drug is available for use in the clinic.”

The Dal researcher notes that the purpose of basic research like the work he is doing is to sort through a long list of possible questions, and identify a handful of useful solutions.  “My research asks, ‘What makes high-risk leukemia different from low-risk leukemia?’  I have made good progress on my answer, and will continue to search for new solutions.”

Mike’s interest in cancer research is a tribute to his sister Liane, who died of non-Hodgkin's lymphoma in 2003. She was 14 years old. “It was a cornerstone in my life,” says Mike. “It gave me a direction. It solidified that I wanted to focus on cancer.”

“Today,” he adds, “my research gives me a sense of pride.”

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