Professor Francisco N. Barrera’s lab in the Department of Biochemistry and Cellular and Molecular Biology is engineering peptides that can target cancer cells.
Researchers from the University of Tennessee, Knoxville, are working on a promising strategy to make therapies targeting cancer smarter and more precise, with peptides that switch on in the acidic environment surrounding tumors.
Professor Francisco N. Barrera’s lab in the Department of Biochemistry and Cellular and Molecular Biology has created a class of peptides that can sense acidity and insert into cell membranes only under those conditions.
“Healthy tissues are typically less acidic, so these peptides may offer a way to deliver therapies more selectively to cancer cells while reducing unwanted effects on normal tissues,” Barrera explained.
He and former student Jen Rybak (BS chemistry ’17, PhD biochemistry ’25) focus on those TMAC (transmembrane allosteric conditional membrane) peptides in a review recently published in a special issue of Chemical Reviews. One of the most prestigious academic journals in the field, the publication acts as a premier “encyclopedia” of chemistry, inviting world-leading experts to write comprehensive, field-defining summaries that shape the direction of future research.
Barrera’s work has helped advance the development of peptides that can be engineered to target membrane receptors that help cancer cells metastasize. One especially important target is EphA2, a receptor that is often overactive in aggressive cancers and has been linked to cell metastasis, invasion, and resistance to treatment. By designing peptides that respond to acidity and interact with receptors such as EphA2, researchers hope to create a new generation of molecules that can both detect tumors and interfere with the signals that make them dangerous.
“Advances in membrane biophysics, peptide design, and cancer biology are converging to make that vision increasingly realistic,” Barrera said. “The work points toward future ‘intelligent’ agents—molecules that could one day help both find and fight metastatic cancer.”
Barrera’s research has been supported by two National Institutes for Health grants, and as a doctoral student Rybak received a Graduate Advancement, Training and Education (GATE) fellowship, which supports collaborative research between UT and Oak Ridge National Laboratory. She is now a core scientist at UT’s Advanced Microscopy and Imaging Center.
Their work also benefited from the UT Biomembranes Community of Scholars, which provides graduate training opportunities and critical research mass to catalyze the exchange of scientific ideas. To foster new interdisciplinary research, Barrera also recently returned from a sabbatical at the Max Planck Institute of Colloids and Interfaces in Postdam, Germany.
The Barrera Lab is carrying out additional fundamental research that could lead to biomedical breakthroughs to curb fungal infections. Specifically, it has elucidated the mode of action of candidalysin, a virulence factor that is key for infections by the fungal pathogen Candida albicans, such as invasive candidiasis, thrush, and vaginal yeast infections.
by Amy Beth Miller