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Lister studies genetic mutations in zebrafish in an effort to treat or prevent melanoma

James Lister, Ph.D.

Massey researcher James Lister, Ph.D., studies proteins in zebrafish that are linked to cancer development in an effort to inform the biology and treatment of melanoma and other genetic diseases.

Lister joined VCU Massey Cancer Center as a member of the Cancer Molecular Genetics research program in 2018 and is an assistant professor in the Department of Human and Molecular Genetics at the VCU School of Medicine.

His primary research is centered on the microphthalmia-associated transcription factor (MITF) in zebrafish models and how its activity correlates to the development of melanoma, the most dangerous form of skin cancer. Transcription factors are proteins that regulate the expression of genetic information within the cell.

“There are two types of MITF: MITFa and MITFb. The MITFa gene is kind of a master regulator of melanocytes, the skin cells that produce melanin and are linked to the development of melanoma,” Lister said.

In zebrafish, Lister’s research has determined that a particular mutation in the MITFa gene that decreases its function, when combined with the most common genetic mutation in human melanoma cells, allows for signaling pathways to lead to the development of melanoma.

These findings suggest that modulation of MITF activity is a key factor in the onset and progression of melanoma, and Lister hopes to be able to learn more about how regulation of MITF might be leveraged to treat or prevent human melanoma.

“No one yet has really examined MITF mutations in melanoma in the context of a model organism, not even in a mouse model,” Lister said.

Zebrafish are freshwater fish in the minnow family. They share 70 percent of genes found in humans, and are much smaller and cheaper to maintain than mice, making them effective model organisms for human diseases like cancer, according to the National Institutes of Health.

There are still many cancers yet to be modeled in zebrafish, and Lister is hopeful that he can continue to study genetic mutations in the MITF family as a means to inform the development of novel treatments for other genetic diseases in addition to melanoma.

“It’s always exciting to see what new things can be accomplished with expanding technology,” Lister said. “The idea that we’re trying to make targeted mutations in zebrafish was unheard of even 10 years ago.”

He currently holds grant funding from the National Institute of Neurological Disease and Stroke as a co-investigator on a study examining the role of genetic mechanisms in CNS myelination, and from the MEDARVA Foundation as a co-principal investigator on a study of a craniofacial birth defect using zebrafish.

Lister has previously received more than $1 million in grant funding for various research projects, including $475,000 from the National Institute of Child Health and Human Development to study site-specific transgenesis in zebrafish.

Lister grew up in Ellensburg, Washington. He attended college at Pomona College in southern California. Initially, he thought he would pursue a career in medicine, but by sophomore year his interests had transitioned to cellular biology.

Following the completion of his bachelor’s degree in biology, Lister studied gene regulation in red blood cells while earning a Ph.D. in biology from Harvard University. It was in Cambridge that he found his calling in developmental biology and decided he wanted to conduct genetic research in whole organisms. Lister had previously worked with fruit flies while on a laboratory rotation and began studying zebrafish as model organisms during his post-doctoral fellowship at the University of Washington.

He has been published in more than 25 peer-reviewed journals including Development, Genes & Development and Genome Biology. Lister received an Outstanding Teaching Award from the VCU School of Medicine in 2008 and the Vaile Prize in Biology from Pomona College. He is a member of the PanAmerican Society for Pigment Cell Research, Society for Developmental Biology and Zebrafish Disease Models Society.

Lister met his wife in Washington and together they live in downtown Richmond.

Written by: Blake Belden

Posted on: November 26, 2018