After winning a series of awards this year, Assistant Professor of Hematology, Oncology, and Blood and Marrow Transplantation Colin Kenny, PhD, has received a five-year, $3 million National Institutes of Health R01 grant to investigate the earliest cellular changes that drive melanoma metastasis.
The R01 is one of the most competitive forms of NIH funding, supporting investigator-initiated research programs, and the award signals strong confidence in the direction of Kenny’s lab.
For patients with melanoma, the greatest danger comes when cancer cells leave the original tumor and establish new tumors elsewhere in the body. Kenny’s research focuses on the biological changes that make that transformation possible.
“We are studying melanoma cell plasticity and how cells change their behavior as they metastasize,” Kenny said. “A cell has to proliferate to form a primary tumor, then some of those cells have to change their phenotype to become invasive. If they reach a secondary site and form a metastasis, they need to switch back again to a proliferative state. We study that process—how cells go from growth to movement and then back to growth again.”
Kenny’s team has identified two genes potentially responsible for that switch, TFE3 and TFAP2B, that appear to work together to push melanoma cells out of a stable, proliferative state and into an invasive one.
Their preliminary data suggest a specific form of TFE3 is stabilized in invasive melanoma cells, and that knocking it out reduces both invasion and the cells’ ability to seed new tumors in other parts of the body. The new grant will test how these two genes interact to control that transition, and whether disrupting them could stop invasion before it starts.
The work builds on research Kenny began as a postdoctoral researcher in Robert Cornell’s, PhD, lab at Iowa’s Department of Anatomy in Cell Biology (now in the University of Washington, Seattle), tracing how embryonic neural crest cells migrate through the body. The project also brings together collaborators from across the university, including Chris Stipp, PhD, Eric Van Otterloo, PhD, and Ronald Weigel, MD, PhD, whose expertise will support the study.
Kenny’s lab is testing the theory using two model systems. Zebrafish embryos are transparent, which allows researchers to watch melanoma cells travel through the bloodstream, exit blood vessels, and settle into new tissue in real time. Then, mouse models will help the team explore longer-term questions about how cells survive in the bloodstream and eventually grow into full metastatic tumors.
For Kenny, the long-term goal is to understand what happens before a metastasis is detectable, while there’s a chance to stop it.
Melanoma is also part of a larger, more immediate problem for the state. Iowa has the second-highest cancer incidence rate in the country, and it’s one of the only states where that rate continues to increase.
“Melanoma contributes to Iowa’s growing cancer rate,” Kenny said. “So, it’s close to our hearts to study melanoma in this community.”