What happens when a discovery in cancer biology leads scientists somewhere entirely unexpected?
In a new episode of Science@UH, Sanford Markowitz, MD, PhD, a member of Case CCC's Cancer Genomics and Epigenomics Program and the Ingalls Professor of Genetics at the CWRU School of Medicine, and Andrew Pieper, MD, PhD, Associate Director of the Medical Scientist Training Program at the CWRU School of Medicine and board-certified psychiatrist and neuroscientist at University Hospitals, share the story of how research into tissue repair and regeneration opened a promising new avenue for protecting the brain.
Markowitz's early cancer work identified 15-PGDH, an enzyme involved in tissue stem cell regulation. Over the years, an interesting biological contrast developed: in cancer, higher 15-PGDH can be protective because it reduces pro-tumor PGE2 signaling. In tissue repair, the temporary inhibition of 15-PGDH can increase PGE2 and promote regeneration.
Now, the newer work suggests inhibiting 15-PGDH may also counter processes associated with aging, traumatic brain injury and Alzheimer's disease.
Working with Pieper and a multidisciplinary team, the researchers found that 15-PGDH activity is elevated in Alzheimer’s disease, traumatic brain injury and aging, where it is associated with inflammation and damage to the blood-brain barrier. In preclinical models, inhibiting the enzyme helped protect the blood-brain barrier, reduce damaging reactive oxygen species and preserve cognition.
Published in proceedings of the National Academy of Sciences in 2025 and recognized with the 2025 Cozzarelli Prize in Biomedical Sciences, the findings point toward a potential new therapeutic strategy for Alzheimer’s disease and traumatic brain injury and showcase a compelling example of the unexpected paths scientific discovery can take—and how insights originating in cancer biology can create possibilities well beyond cancer.
Listen to the Science@UH podcast to hear Markowitz and Pieper explain how the collaboration came together, what they are learning about the relationship between inflammation and brain health, and where the research could lead next.