Wednesday, April 12, 2017
Not many undergraduates can say they have worked alongside top scientists in search of what could cause leukemia at a cellular level. But Daniel Mohammadi, a senior forensic science major who works in the Tombes Lab with mentor Sarah Rothschild, Ph.D., an assistant professor in the Department of Biology within the College of Humanities and Sciences, has had this privilege for two years.
Mohammadi, a member of the VCU Honors College, is currently assisting Rothschild in a study that uses zebrafish as a model organism to investigate the development of leukemia in humans. The project, on which Rothschild serves as co-investigator with Seth Corey, M.D., Ph.D., chief of the Division of Pediatric Hematology and Oncology in the VCU School of Medicine, and Robert Tombes, Ph.D., vice provost for VCU Life Sciences, was funded by a $50,000 Massey Cancer Center Pilot Project grant.
Rothschild, Mohammadi and other investigators are researching if high levels of CaM kinase II, an enzyme that plays a role in jump-starting much of the body’s development, could possibly cause higher rates of leukemia. The enzyme is a protein that is activated when it binds with calcium.
Mohammadi said the study is a large stride toward finding exact causes of cancerous mutations.
“The work is important to science in general because it could help determine how cells react to stimuli that cause cancer and the mechanisms behind that,” he said.
A cancer catalyst
The blue and gold striped, inch-long zebrafish seems to be as different from humans as a species can be, but scientists have found many useful similarities. Eighty-four percent of genes known to be associated with human disease have a zebrafish counterpart. A zebrafish female can also produce a few hundred eggs per week, which gives researchers large sample sizes.
“The ability to test on something as easy to manipulate as zebrafish is invaluable,” Mohammadi said. “The understanding of these disease pathways is crucial for us to extrapolate and implement for human research.”
The Tombes lab found the perfect model, but some work had to be done to “set the canvas” for testing the impacts of CaM kinase II, Mohammadi said. Researchers then selectively bred two zebrafish test groups — an experimental and a control.
Both groups were bred to have a mutation that caused the absence of the body’s main defense against cancer, tumor protein P53. Commonly known as P53, this grouping of various proteins stops the formation of cancer cells.
Think of P53 as a checkpoint regulator. It tells a cancerous cell to kill itself.
“Think of P53 as a checkpoint regulator. It tells a cancerous cell to kill itself. Without it, the cells would replicate,” Mohammadi said.
On top of not having the cancer fighting power of P53, the experimental group was bred to have a hyperactive form of CaM kinase II.
Breeding both test groups without the development of P53 provided the perfect environment for cancer to thrive and “set the stage” to observe CaM kinase II in action, Mohammadi said. The theory is that the CaM kinase II experimental group would be more susceptible to cancer, even though the control group also lacks a key protection from the disease.
The researchers have found incidences of cancer in CaM kinase II test groups, but aren’t yet sure which type. Based off of pathology analysis, it could be either leukemia or lymphoma. Both are cancers of the blood but in leukemia, cancer cells are mainly in the marrow and blood. In lymphoma, they tend to be in the lymph nodes and other tissues.
Rothschild said the number of zebrafish with cancer is too low at this point to make definitive conclusions about the relation between the disease and CaM kinase II. Researchers are working on raising more fish to test.
Previous studies have indicated CaM kinase II may be a causal factor in the development of acute and chronic myeloid leukemia, which affects the white blood cells.
A valuable experience
Mohammadi was awarded the Undergraduate Research Opportunities Program summer fellowship for his work with Rothschild. During his time in the lab, he has learned useful research skills such as performing injections, designing and executing his own experiments, and how to use lab equipment.
Mohammadi, who plans to attend the University of Texas Southwestern Medical School to study orthopedics and sports medicine after graduation, said he values his experience in cancer research.
“What I’ve gotten the most out of this experience is a new level of respect for people in the research field, especially since I want to be a physician,” he said. “I may not be directly involved in research but I definitely can try to collaborate with them.”
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