Sanford Markowitz, MD, PhD, member of Case CCC’s Cancer Genomics and Epigenomics Program, and collaborator Andrew Pieper, MD, PhD, of University Hospitals Harrington Discovery Institute and Professor in the departments of Psychiatry, Pathology, and Neurosciences at Case Western Reserve University School of Medicine, received the 2025 Cozzarelli Prize in Biomedical Sciences from PNAS for their study, Inhibiting 15-PGDH blocks blood-brain barrier deterioration and protects mice from Alzheimer’s disease and traumatic brain injury. The prize recognizes one outstanding paper in each of six scientific classes published by PNAS each year.
The study demonstrates that inhibiting the enzyme 15-PGDH using the small molecule SW033291, developed by Markowitz and collaborators, protects against neurodegeneration and cognitive decline in models of Alzheimer's disease and traumatic brain injury. Mechanistically, 15-PGDH inhibition suppresses damaging inflammatory activity in brain myeloid cells, preserves blood–brain barrier integrity, and blocks downstream neurodegeneration.
This work builds on earlier discoveries from the Case GI SPORE, where Markowitz and colleagues—including former Case CCC directors James K. V. Willson, MD, and Stanton Gerson, MD, now Dean of Case Western Reserve University School of Medicine—identified SW033291 as a potent inhibitor of 15-PGDH and demonstrated its ability to activate tissue stem cell–mediated regeneration (Science, 2015). The current study extends earlier work on 15-PGDH by showing that inhibition of this pathway can protect blood-brain barrier integrity in addition to supporting regenerative responses shown in earlier studies. More broadly, the work illustrates how pathways discovered in cancer can serve as foundational, cross-disease therapeutic targets with relevance well beyond oncology.
“This recognition underscores the power of discovery science that begins in cancer biology and extends into fundamentally new ways of treating disease,” said Gary Schwartz, MD, Case CCC Director. “By targeting a pathway first defined in cancer and regenerative research, this work opens a new therapeutic direction—one that protects tissue by modulating inflammation rather than attempting to reverse damage after it occurs. That has implications not only for neurodegenerative disease, but for how we think about intervention across multiple disease states.”
Case CCC Immune Oncology Program member Amar Desai, PhD, was a key contributor to both the 2015 and 2025 studies.
The 2025 Cozzarelli Prize recipients were recognized during the National Academy of Sciences awards ceremony on April 26, 2026.