Recent findings from Assistant Professor of biomedical engineering Karmella Haynes may chart a new course in cancer treatment with the use of custom-built, therapeutic proteins.
The work, published January 9 in the Nature Partner Journal Genomic Medicine, details how Haynes and her co-authors engineered proteins that activate anti-cancer genes in cancer cells.
Haynes is the principal investigator and senior author of the article, titled “Regulation of cancer epigenomes with a histone-binding synthetic transcription factor.” David Nyer, a research technician with the School of Biological and Health Systems Engineering is the lead author. Biological design graduate students Rene Daer and Daniel Vargas and biomedical engineering alumna Caroline Hom are co-authors.
Two foundational discoveries from the broader research community paved the way for the team’s research. When cancer cells propagate, they shut down anti-cancer genes by altering histones, a type of protein involved in chromosome packaging. Additionally, the discovery of histone-reading proteins with the ability to detect cancer markers aided the research.
“Using this information, we designed a custom-built protein that could attach to the modified histones and re-boot the activity of anti-cancer genes,” says Haynes.
While witnessing the activation of anti-cancer genes was exciting, Haynes notes that the real interesting discovery was that their protein could find its target genes even when the histone, which it attaches to, was far away from the beginning of the gene.
“We now have a better understanding of how our engineered protein works and how to make it even more effective,” she adds.
Prior to these findings, researchers and clinicians have used chemical drugs to target chromosomes in cancer cells and to stimulate anti-cancer genes. This marks the first time anyone has designed a protein that controls genes by attaching to the specially-modified histones in cancer cells.
“Our research is a proof-of-concept and provides a new blueprint for custom-built, therapeutic proteins,” says Haynes.
The research builds on decades of investigation into the molecules that make up human chromosomes, as well as work completed by Haynes at Harvard University in 2011. There she engineered a semi-artificial protein with the ability to control genes within cancer cells, and expanded the research upon arriving at ASU to monitor the protein’s effect on scores of genes within bone, brain and blood cancer cells.
“We built DNA that encoded the artificial protein, delivered this DNA into the cells, and once the DNA entered the nucleus the cancer cells began producing our protein,” says Haynes. “We discovered that the artificial protein could activate anti-cancer genes in all three cancer cell types.”
Haynes acknowledges research assistance from Joshua LaBaer, Jason Kramer, Jason Steel, Jin Park, Natalia Briones, Kristina Buss and Shanshan Yang from the Biodesign Institute, as well as Melissa Wilson-Sayres and Kimberly Olney from the School of Life Sciences for their analytical support.